193 results on '"Sherry Liu"'
Search Results
2. Galectins-1 and-3 Increase in Equine Post-traumatic Osteoarthritis
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Heidi L. Reesink, Alan J. Nixon, Jin Su, Sherry Liu, Ryan M. Sutton, Sabine Mann, Ashlee E. Watts, and Ryan P. Peterson
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inflammatory arthritis ,cartilage ,synovium ,chondrocyte ,synoviocyte ,horse ,Veterinary medicine ,SF600-1100 - Abstract
Galectins are potent regulators of cell adhesion, growth and apoptosis in diverse cell types, including chondrocytes and synovial fibroblasts. Elevations in synovial fluid galectin-3 have been observed in rheumatoid arthritis, juvenile idiopathic arthritis and experimental inflammatory arthritis in animal models, whereas galectin-1 is thought to be protective. Less is known about galectins-1 and-3 in osteoarthritis (OA). Therefore, the purpose of this study was: (1) to determine whether galectin-1 and-3 synovial fluid concentrations and synovial membrane and cartilage histochemical staining were altered following osteochondral injury in an experimental equine osteoarthritis (OA) model and (2) to measure galectin-1 and-3 mRNA expression and synovial fluid concentrations in naturally occurring equine carpal OA. Synovial fluid galectin-1 and-3 concentrations were quantified using custom ELISAs in two research horse cohorts undergoing experimental OA induction (n = 5 and 4) and in a cohort of horses with naturally occurring carpal OA (n = 57). Galectin mRNA expression in synovial membrane and cartilage tissue obtained from carpal joints of horses with naturally occurring OA was measured using RT-qPCR, and galectin immunostaining was assessed in synovial membrane and osteochondral tissues in the experimental model (n = 5). Synovial fluid galectin-1 and-3 concentrations increased following experimental carpal osteochondral fragmentation. Cartilage galectin-1 mRNA expression increased with OA severity in naturally occurring disease. The superficial zone of healthy articular cartilage stained intensely for galectin-3 in sham-operated joints, whereas galectin-1 staining was nearly absent. Chondrocyte galectin-1 and-3 immunoreactivity increased following cartilage injury, particularly in galectin-1 positive chondrones. Galectins-1 and-3 are present in healthy equine synovial fluid and increase following post-traumatic OA. Healthy superficial zone chondrocytes express galectin-3, whereas galectin-1 chondrocyte staining is limited predominantly to chondrones and injured cartilage. Further work is needed to clarify the functions of galectins-1 and-3 in healthy and OA joints.
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- 2018
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3. Relationship between esomeprazole dose and timing to heartburn resolution in selected patients with gastroesophageal reflux disease
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Roy C Orlando, Sherry Liu, and Marta Illueca
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Roy C Orlando1, Sherry Liu2, Marta Illueca31Department of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA, 2Department of Statistics and Informatics, 3Department of Clinical Development, AstraZeneca LP, Wilmington, DE, USAObjective: To increase response rates to therapy by increasing the dosage of proton pump inhibitor (PPI) therapy in patients with gastroesophageal reflux disease (GERD) whose symptoms are predominantly associated with acid reflux.Methods: In this double-blind, randomized, proof-of-concept study, 369 patients with GERD and moderate heartburn lasting ≥three days/week, a history of response to antacids/acid suppression therapy, and a positive esophageal acid perfusion test result were randomized to esomeprazole 20 or 40 mg once daily, or to 40 mg twice daily for four weeks. Heartburn symptom relief/resolution was subsequently evaluated.Results: In this study population, no relationship was apparent between esomeprazole dosage and efficacy variables for sustained heartburn resolution (seven days without symptoms) at week 4 (48.0%, 44.0%, and 41.4% for esomeprazole 20 mg once daily, 40 mg once daily, and 40 mg twice daily, respectively). Nocturnal heartburn resolution with esomeprazole 40 mg twice daily showed a numeric improvement trend versus esomeprazole 20 and 40 mg once daily, but this was not statistically significant.Conclusions: Heartburn resolution rates at four weeks were similar for all esomeprazole dosages and comparable with rates reported previously, suggesting a plateau effect in terms of clinical response to acid suppression with PPI therapy in this population of selected GERD patients.Keywords: acid suppressive therapy, GERD, proton pump inhibitor
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- 2010
4. Counterfactual World Modeling for Physical Dynamics Understanding.
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Rahul Venkatesh, Honglin Chen, Kevin T. Feigelis, Daniel M. Bear, Khaled Jedoui, Klemen Kotar, Felix J. Binder, Wanhee Lee, Sherry Liu, Kevin A. Smith, Judith E. Fan, and Daniel L. K. Yamins
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- 2023
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5. Reinhabiting in Huaniao Island
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Ye (Sherry) Liu
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General Engineering - Abstract
This paper argues that the loss of cultural memories is an essential issue that challenges the social transformation in Chinese rural regeneration and proposes 'reinhabiting the place' as a potential to empower the traditional community and contribute to renewing cultural connections. Based on my experience of the residency period and other artists' practice on the Huaniao Island, this portfolio explores 'culture aphasia' in the rural revitalization of Huaniao island. It investigates the 2nd Huaniao Island International Public Art Festival's social engagement practice and explores how creative strategies operate to reinhabit the place and re-establish cultural connections. The text explores how artists work proactively with residents and visitors, reconstruct the cultural memories, and renew affective engagement of the community.
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- 2022
6. Instrumented nanoindentation in musculoskeletal research
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Shaopeng Pei, Yilu Zhou, Yihan Li, Tala Azar, Wenzheng Wang, Do-Gyoon Kim, and X. Sherry Liu
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Biophysics ,Molecular Biology ,Bone and Bones - Abstract
Musculoskeletal tissues, such as bone, cartilage, and muscle, are natural composite materials that are constructed with a hierarchical structure ranging from the cell to tissue level. The component differences and structural complexity, together, require comprehensive multiscale mechanical characterization. In this review, we focus on nanoindentation testing, which is used for nanometer to sub-micrometer length scale mechanical characterization. In the following context, we will summarize studies of nanoindentation in musculoskeletal research, examine the critical factors that affect nanoindentation testing results, and briefly summarize other commonly used techniques that can be conjoined with nanoindentation for synchronized imaging and colocalized characterization.
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- 2022
7. Systematic review: Can non-mydriatic cameras accurately detect diabetic retinopathy?
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Bedard, Chloe, (Sherry) Liu, Siying, Patterson, Christopher, Gerstein, Hertzel, and Griffith, Lauren
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- 2017
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8. Activating <scp>EGFR</scp> Signaling Attenuates Osteoarthritis Development Following Loading Injury in Mice
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Tao Gui, Yulong Wei, Lijun Luo, Jun Li, Leilei Zhong, Lutian Yao, Frank Beier, Charles L. Nelson, Andrew Tsourkas, X. Sherry Liu, Motomi Enomoto‐Iwamoto, Feifan Yu, Zhiliang Cheng, and Ling Qin
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Endocrinology, Diabetes and Metabolism ,Orthopedics and Sports Medicine - Abstract
Posttraumatic osteoarthritis (PTOA) results in joint pain, loss of joint function, and impaired quality of daily life in patients with limited treatment options. We previously demonstrated that epidermal growth factor receptor (EGFR) signaling is essential for maintaining chondroprogenitors during articular cartilage development and homeostasis. Here, we used a nonsurgical, loading-induced PTOA mouse model to investigate the protective action of EGFR signaling. A single bout of cyclic tibial loading at a peak force of 6 N injured cartilage at the posterior aspect of lateral femoral condyle. Similar loading at a peak force of 9 N ruptured the anterior cruciate ligament, causing additional cartilage damage at the medial compartment and ectopic cartilage formation in meniscus and synovium. Constitutively overexpression of an EGFR ligand, heparin binding EGF-like growth factor (HBEGF), in chondrocytes significantly reduced cartilage injury length, synovitis, and pain after 6 N loading and mitigated medial side cartilage damage and ectopic cartilage formation after 9 N loading. Mechanistically, overactivation of EGFR signaling protected chondrocytes from loading-induced apoptosis and loss of proliferative ability and lubricant synthesis. Overexpressing HBEGF in adult cartilage starting right before 6 N loading had similar beneficial effects. In contrast, inactivating EGFR in adult cartilage led to accelerated PTOA progression with elevated cartilage Mankin score and synovitis score and increased ectopic cartilage formation. As a therapeutic approach, we constructed a nanoparticle conjugated with the EGFR ligand TGFα. Intra-articular injections of this nanoconstruct once every 3 weeks for 12 weeks partially mitigated PTOA symptoms in cartilage and synovium after 6 N loading. Our findings demonstrate the anabolic actions of EGFR signaling in maintaining articular cartilage during PTOA development and shed light on developing a novel nanomedicine for PTOA. © 2022 American Society for Bone and Mineral Research (ASBMR).
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- 2022
9. Distinct Responses of Modeling‐ and <scp>Remodeling‐Based</scp> Bone Formation to the Discontinuation of Intermittent Parathyroid Hormone Treatment in Ovariectomized Rats
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Wenzheng Wang, Tala Azar, Wei‐Ju Tseng, Shaopeng Pei, Yilu Zhou, Xi Jiang, Nathaniel Dyment, and X. Sherry Liu
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Ovariectomy ,Endocrinology, Diabetes and Metabolism ,X-Ray Microtomography ,Rats ,Rats, Sprague-Dawley ,Bone Diseases, Metabolic ,Anabolic Agents ,Bone Density ,Osteogenesis ,Parathyroid Hormone ,Animals ,Female ,Orthopedics and Sports Medicine ,Bone Resorption - Abstract
Anabolic agents, such as intermittent parathyroid hormone (PTH), exert their treatment efficacy through activation of two distinct bone formation processes, namely, remodeling-based bone formation (RBF, bone formation coupled with prior bone resorption) and modeling-based bone formation (MBF, bone formation without prior activation of bone resorption). However, if not followed by an antiresorptive agent, treatment benefit was quickly lost upon withdrawal from anabolic agents. By using in vivo micro-computed tomography imaging and multiplex cryohistology with sequential immunofluorescence staining, we investigated the temporal response of newly formed bone tissue from MBF and RBF and the preexisting bone tissue to withdrawal from PTH treatment and the associated cellular activity in an ovariectomized (OVX) rat model. We first demonstrated continued mineral apposition at both RBF and MBF sites following PTH discontinuation, resulting in an extended anabolic effect after 1-week withdrawal from PTH. It was further discovered that MBF sites had a greater contribution than RBF sites to the extended anabolic effect upon early withdrawal from PTH, evidenced by a higher percentage of alkaline phosphatase-positive (ALP+) surfaces and far greater bone formation activity at MBF versus RBF sites. Furthermore, significant bone loss occurred after 3 weeks of discontinuation from PTH, resulting from marked loss of newly formed bone tissue from RBF and preexisting bone tissue prior to treatment. In contrast, MBF surfaces had a delayed increase of tartrate-resistant acid phosphatase activity following PTH discontinuation. As a result, newly formed bone tissue from MBF had greater resistance to PTH discontinuation-induced bone loss than those from RBF and preexisting bone. Understanding various responses of two distinct bone formation types and preexisting bone to anabolic treatment discontinuation is critical to inform the design of follow-up treatment or cyclic treatment strategies to maximize treatment benefit of anabolic agents. © 2022 American Society for Bone and Mineral Research (ASBMR).
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- 2022
10. Ordinary Differential Equations and Boundary Value Problems: Volume II: Boundary Value Problems
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John R Graef, Johnny Henderson, Lingju Kong, Xueyan Sherry Liu, John R Graef, Johnny Henderson, Lingju Kong, and Xueyan Sherry Liu
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- 2018
11. Ordinary Differential Equations and Boundary Value Problems: Volume I: Advanced Ordinary Differential Equations
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John R Graef, Johnny Henderson, Lingju Kong, Xueyan Sherry Liu, John R Graef, Johnny Henderson, Lingju Kong, and Xueyan Sherry Liu
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- 2018
12. Huaniao Island Public Art Festival: A Site for Social Encounter and Cultural Exchange
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Ye (Sherry) Liu, Marnie Badham, and Dominic Redfern
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General Medicine - Published
- 2022
13. In vivo precision of digital topological skeletonization based individual trabecula segmentation (ITS) analysis of trabecular microstructure at the distal radius and tibia by HR-pQCT.
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Bin Zhou, Zhendong Zhang, Ji Wang, Y. Eric Yu, X. Sherry Liu, Kyle K. Nishiyama, Mishaela R. Rubin, Elizabeth Shane, John P. Bilezikian, and X. Edward Guo
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- 2016
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14. Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss
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Yu, Wei, Zhong, Leilei, Yao, Lutian, Wei, Yulong, Gui, Tao, Li, Ziqing, Kim, Hyunsoo, Holdreith, Nicholas, Jiang, Xi, Tong, Wei, Dyment, Nathaniel, X. Sherry, Liu, Yang, Shuying, Choi, Yongwon, Ahn, Jaimo, and Qin, Ling
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Medical research ,Medicine, Experimental ,Hematopoietic stem cells -- Physiological aspects -- Health aspects ,Osteoclasts (Biology) -- Health aspects -- Physiological aspects ,Fat cells -- Physiological aspects -- Health aspects ,Bone remodeling -- Research ,Health care industry - Abstract
Bone is maintained by coupled activities of bone-forming osteoblasts/osteocytes and bone-resorbing osteoclasts. Alterations in this relationship can lead to pathologic bone loss such as osteoporosis. It is well known that osteogenic cells support osteoclastogenesis via production of RANKL. Interestingly, our recently identified bone marrow mesenchymal cell population--marrow adipogenic lineage precursors (MALPs) that form a multidimensional cell network in bone--was computationally demonstrated to be the most interactive with monocyte-macrophage lineage cells through high and specific expression of several osteoclast regulatory factors, including RANKL. Using an adipocyte-specific Adipoq-Cre to label MALPs, we demonstrated that mice with RANKL deficiency in MALPs have a drastic increase in trabecular bone mass in long bones and vertebrae starting from 1 month of age, while their cortical bone appears normal. This phenotype was accompanied by diminished osteoclast number and attenuated bone formation at the trabecular bone surface. Reduced RANKL signaling in calvarial MALPs abolished osteolytic lesions after LPS injections. Furthermore, in ovariectomized mice, elevated bone resorption was partially attenuated by RANKL deficiency in MALPs. In summary, our studies identified MALPs as a critical player in controlling bone remodeling during normal bone metabolism and pathological bone loss in a RANKL-dependent fashion., Introduction Bone is a dynamic tissue, constantly undergoing remodeling through coupled activities of bone-resorbing osteoclasts and bone-forming osteoblasts/osteocytes. A shift in the balance of these 2 actions toward resorption leads [...]
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- 2021
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15. Short Cyclic Regimen With Parathyroid Hormone ( <scp>PTH</scp> ) Results in Prolonged Anabolic Effect Relative to Continuous Treatment Followed by Discontinuation in Ovariectomized Rats
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Wei‐Ju Tseng, Wonsae Lee, Hongbo Zhao, Yang Liu, Wenzheng Wang, Chantal MJ Bakker, Yihan Li, Carlos Osuna, Wei Tong, Luqiang Wang, Xiaoyuan Ma, Ling Qin, and X Sherry Liu
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Anabolic Agents ,Bone Density ,Parathyroid Hormone ,Ovariectomy ,Endocrinology, Diabetes and Metabolism ,Animals ,Humans ,Estrogens ,Female ,Orthopedics and Sports Medicine ,Article ,Rats - Abstract
Despite the potent effect of intermittent parathyroid hormone (PTH) treatment on promoting new bone formation, bone mineral density (BMD) rapidly decreases upon discontinuation of PTH administration. To uncover the mechanisms behind this adverse phenomenon, we investigated the immediate responses in bone microstructure and bone cell activities to PTH treatment withdrawal and the associated long-term consequences. Unexpectedly, intact female and estrogen-deficient female rats had distinct responses to the discontinuation of PTH treatment. Significant tibial bone loss and bone microarchitecture deterioration occurred in estrogen-deficient rats, with the treatment benefits of PTH completely lost 9 weeks after discontinuation. In contrast, no adverse effect was observed in intact rats, with sustained treatment benefit 9 weeks after discontinuation. Intriguingly, there is an extended anabolic period during the first week of treatment withdrawal in estrogen-deficient rats, during which no significant change occurred in the number of osteoclasts, whereas the number of osteoblasts remained elevated compared with vehicle-treated rats. However, increases in number of osteoclasts and decreases in number of osteoblasts occurred 2 weeks after discontinuation of PTH treatment, leading to significant reduction in bone mass and bone microarchitecture. To leverage the extended anabolic period upon early withdrawal from PTH, a cyclic administration regimen with repeated cycles of on and off PTH treatment was explored. We demonstrated that the cyclic treatment regimen efficiently alleviated the PTH withdrawal-induced bone loss, improved bone mass, bone microarchitecture, and whole-bone mechanical properties, and extended the treatment duration. © 2021 American Society for Bone and Mineral Research (ASBMR).
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- 2022
16. Author response for 'Activating EGFR signaling attenuates osteoarthritis development following loading injury in mice'
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null Tao Gui, null Yulong Wei, null Lijun Luo, null Jun Li, null Leilei Zhong, null Lutian Yao, null Frank Beier, null Charles L. Nelson, null Andrew Tsourkas, null X. Sherry Liu, null Motomi Enomoto‐Iwamoto, null Feifan Yu, null Zhiliang Cheng, and null Ling Qin
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- 2022
17. Author response for 'Distinct Responses of Modeling‐ and Remodeling‐Based Bone Formation to the Discontinuation of Intermittent Parathyroid Hormone (PTH) Treatment in Ovariectomized Rats'
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null Wenzheng Wang, null Tala Azar, null Wei‐Ju Tseng, null Shaopeng Pei, null Yilu Zhou, null Xi Jiang, null Nathaniel Dyment, and null X. Sherry Liu
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- 2022
18. Dependence of mechanical properties of trabecular bone on plate–rod microstructure determined by individual trabecula segmentation (ITS)
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Zhou, Bin, Sherry Liu, X., Wang, Ji, Lucas Lu, X., Fields, Aaron J., and Edward Guo, X.
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- 2014
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19. Thermal analysis for a SiGe HBT 40 watt 32 GHz clock 3D memory processor chip stack using diamond heat spreader layers.
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John F. McDonald 0001, Okan Erdogan, Philip Jacob 0001, Paul M. Belemjian, Alexey Gutin, Aamir Zia, Michael Chu, Jin Woo Kim, Ryan Clarke, Nate DeSimone, Sherry Liu, and Russell P. Kraft
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- 2009
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20. Development and validation of an LC-MS/MS method for determination of a novel anticancer agent (CPI-613) in human plasma
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Nageswara Rao Reddy, Vijay Reddy, Asela Boteju, Lakmal Boteju, Troy Voelker, Sherry Liu, and Ke Hu
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Medical Laboratory Technology ,Tandem Mass Spectrometry ,Clinical Biochemistry ,Humans ,Reproducibility of Results ,Antineoplastic Agents ,General Medicine ,General Pharmacology, Toxicology and Pharmaceutics ,Caprylates ,Sulfides ,Analytical Chemistry ,Chromatography, Liquid - Abstract
Background: This article describes the development and validation of a bioanalytical assay to quantify CPI-613 and its major metabolites, CPI-2850 and CPI-1810, in human plasma matrix using LC-MS/MS. Methodology: Sample extraction procedure following protein precipitation with acetonitrile was optimized to extract all three analytes from plasma with maximum recovery. The final extracted supernatants were diluted with water and injected onto an Xbridge C18 (50 × 2.1 mm; 5 μm) column for analysis. The analytes were separated by a gradient elution, and detection was performed on a triple quadrupole mass spectrometer (Sciex API 5000) operating in the negative ion mode. Results: The assay was linear over a range of 50–50,000 ng/ml for CPI-613, 250–250,000 ng/ml for CPI-2850 and 10–10,000 ng/ml for CPI-1810. Benchtop stability was established for 24 h, and four freeze–thaw cycles were evaluated for CPI-613 and its metabolites. Long-term freezer (-60 to -80°C) stability for about 127 days was established in this validation. Mean matrix recovery was more than 80% for all analytes. Conclusion: A robust LC-MS/MS method was developed for the quantification of CPI-613 and its major metabolites. The current assay will be used to support ongoing and future CPI-613 clinical trials.
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- 2022
21. Simultaneous Discrete Intradiploic and Intracerebral Atypical Epidermoid Cysts: Possible Embryological Theories
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Ya Lyn Samantha, Ang, primary, Jiani Sherry, Liu, additional, Chi Long, Ho, additional, Cristine Szu Lyn, Ding, additional, and Jai Prashanth, Rao, additional
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- 2022
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22. Mediation of Cartilage Matrix Degeneration and Fibrillation by Decorin in Post‐traumatic Osteoarthritis
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X. Sherry Liu, Yulong Wei, Chao Wang, David E. Birk, Ling Qin, Lin Han, Li-Hsin Han, Wei Tong, Robert L. Mauck, Renato V. Iozzo, Motomi Enomoto-Iwamoto, Wei Ju Tseng, Biao Han, and Qing Li
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Anabolism ,Decorin ,medicine.medical_treatment ,Immunology ,Osteoarthritis ,Chondrocyte ,Extracellular matrix ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,medicine ,Immunology and Allergy ,Aggrecan ,030203 arthritis & rheumatology ,biology ,Chemistry ,medicine.disease ,carbohydrates (lipids) ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,Endocrinology ,Proteoglycan ,biology.protein - Abstract
OBJECTIVE To elucidate the role of decorin, a small leucine-rich proteoglycan, in the degradation of cartilage matrix during the progression of post-traumatic osteoarthritis (OA). METHODS Three-month-old decorin-null (Dcn-/- ) and inducible decorin-knockout (DcniKO ) mice were subjected to surgical destabilization of the medial meniscus (DMM) to induce post-traumatic OA. The OA phenotype that resulted was evaluated by assessing joint morphology and sulfated glycosaminoglycan (sGAG) staining via histological analysis (n = 6 mice per group), surface collagen fibril nanostructure via scanning electron microscopy (n = 4 mice per group), tissue modulus via atomic force microscopy-nanoindentation (n = 5 or more mice per group) and subchondral bone structure via micro-computed tomography (n = 5 mice per group). Femoral head cartilage explants from wild-type and Dcn-/- mice were stimulated with the inflammatory cytokine interleukin-1β (IL-1β) in vitro (n = 6 mice per group). The resulting chondrocyte response to IL-1β and release of sGAGs were quantified. RESULTS In both Dcn-/- and DcniKO mice, the absence of decorin resulted in accelerated sGAG loss and formation of highly aligned collagen fibrils on the cartilage surface relative to the control (P < 0.05). Also, Dcn-/- mice developed more salient osteophytes, illustrating more severe OA. In cartilage explants treated with IL-1β, loss of decorin did not alter the expression of either anabolic or catabolic genes. However, a greater proportion of sGAGs was released to the media from Dcn-/- mouse explants, in both live and devitalized conditions (P < 0.05). CONCLUSION In post-traumatic OA, decorin delays the loss of fragmented aggrecan and fibrillation of cartilage surface, and thus, plays a protective role in ameliorating cartilage degeneration.
- Published
- 2020
23. Type III collagen is a key regulator of the collagen fibrillar structure and biomechanics of articular cartilage and meniscus
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Mitsuo Yamauchi, Michele Marcolongo, Kevt’her Hoxha, Becky K. Brisson, X. Sherry Liu, Chao Wang, Qing Li, Masahiko Terajima, Susan W. Volk, Motomi Enomoto-Iwamoto, Abby M. Goldberg, Biao Han, and Lin Han
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Cartilage, Articular ,Male ,0301 basic medicine ,Type II collagen ,Haploinsufficiency ,Meniscus (anatomy) ,Microscopy, Atomic Force ,Fibril ,Mechanotransduction, Cellular ,Article ,Collagen Type I ,Chondrocyte ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Extracellular ,medicine ,Animals ,Humans ,Meniscus ,Mechanotransduction ,Collagen Type II ,Molecular Biology ,Aggrecan ,Chemistry ,Fibrillogenesis ,musculoskeletal system ,Biomechanical Phenomena ,Extracellular Matrix ,Collagen Type III ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Biophysics - Abstract
Despite the fact that type III collagen is the second most abundant collagen type in the body, its contribution to the physiologic maintenance and repair of skeletal tissues remains poorly understood. This study queried the role of type III collagen in the structure and biomechanical functions of two structurally distinctive tissues in the knee joint, type II collagen-rich articular cartilage and type I collagen-dominated meniscus. Integrating outcomes from atomic force microscopy-based nanomechanical tests, collagen fibril nanostructural analysis, collagen cross-link analysis and histology, we elucidated the impact of type III collagen haplodeficiency on the morphology, nanostructure and biomechanical properties of articular cartilage and meniscus in Col3a1+/- mice. Reduction of type III collagen leads to increased heterogeneity and mean thickness of collagen fibril diameter, as well as reduced modulus in both tissues, and these effects became more pronounced with skeletal maturation. These data suggest a crucial role of type III collagen in mediating fibril assembly and biomechanical functions of both articular cartilage and meniscus during post-natal growth. In articular cartilage, type III collagen has a marked contribution to the micromechanics of the pericellular matrix, indicating a potential role in mediating the early stage of type II collagen fibrillogenesis and chondrocyte mechanotransduction. In both tissues, reduction of type III collagen leads to decrease in tissue modulus despite the increase in collagen cross-linking. This suggests that the disruption of matrix structure due to type III collagen deficiency outweighs the stiffening of collagen fibrils by increased cross-linking, leading to a net negative impact on tissue modulus. Collectively, this study is the first to highlight the crucial structural role of type III collagen in both articular cartilage and meniscus extracellular matrices. We expect these results to expand our understanding of type III collagen across various tissue types, and to uncover critical molecular components of the microniche for regenerative strategies targeting articular cartilage and meniscus repair.
- Published
- 2020
24. Author response for 'Short Cyclic Regimen with Parathyroid Hormone ( PTH ) Results in Prolonged Anabolic Effect Relative to Continuous Treatment Followed by Discontinuation in Ovariectomized Rats'
- Author
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null Wei‐Ju Tseng, null Wonsae Lee, null Hongbo Zhao, null Yang Liu, null Wenzheng Wang, null Chantal M. J. Bakker, null Yihan Li, null Carlos Osuna, null Wei Tong, null Luqiang Wang, null Xiaoyuan Ma, null Ling Qin, and null X. Sherry Liu
- Published
- 2021
25. Type and orientation of yielded trabeculae during overloading of trabecular bone along orthogonal directions
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Shi, Xiutao, Sherry Liu, X., Wang, Xiang, Edward Guo, X., and Niebur, Glen L.
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- 2010
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26. The critical role of Hedgehog-responsive mesenchymal progenitors in meniscus development and injury repair
- Author
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Fanxin Long, Yulong Wei, Lin Han, Leilei Zhong, Eiki Koyama, Wei Yu, Nathaniel A. Dyment, Lutian Yao, Jaimo Ahn, Xiaowei Sherry Liu, Tao Gui, Su Jin Heo, Yejia Zhang, Ling Qin, Robert L. Mauck, Sun H, and Miltiadis H. Zgonis
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Male ,0301 basic medicine ,Pathology ,Time Factors ,Mouse ,Swine ,Gli1 ,meniscus injury ,Osteoarthritis ,Meniscus (anatomy) ,Menisci, Tibial ,Regenerative medicine ,0302 clinical medicine ,Medicine ,Biology (General) ,Mice, Knockout ,education.field_of_study ,integumentary system ,General Neuroscience ,General Medicine ,Osteoarthritis, Knee ,musculoskeletal system ,Stem Cells and Regenerative Medicine ,Tibial Meniscus Injuries ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Swine, Miniature ,Stem cell ,Signal Transduction ,Research Article ,medicine.medical_specialty ,QH301-705.5 ,Science ,Population ,Mesenchymal Stem Cell Transplantation ,Zinc Finger Protein GLI1 ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,lineage tracing ,Animals ,Humans ,Cell Lineage ,Hedgehog Proteins ,Progenitor cell ,education ,Cell Proliferation ,Progenitor ,Wound Healing ,General Immunology and Microbiology ,business.industry ,mesenchymal progenitor ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,medicine.disease ,Disease Models, Animal ,osteoarthritis ,030104 developmental biology ,business ,Developmental Biology - Abstract
Meniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using a Gli1 reporter line, we found that Gli1+ cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1+ cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1+ cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of Gli1-lineage cells. Normally, meniscal tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1+ cells further hindered this repair process. Strikingly, intra-articular injection of Gli1+ meniscal cells or an Hh agonist right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.
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- 2021
27. Author response: The critical role of Hedgehog-responsive mesenchymal progenitors in meniscus development and injury repair
- Author
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Nathaniel A. Dyment, Eiki Koyama, Wei Yu, Tao Gui, Lin Han, Leilei Zhong, Fanxin Long, Su Jin Heo, Xiaowei Sherry Liu, Ling Qin, Miltiadis H. Zgonis, Yulong Wei, Yejia Zhang, Robert L. Mauck, Jaimo Ahn, Sun H, and Lutian Yao
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medicine.anatomical_structure ,business.industry ,Mesenchymal stem cell ,Medicine ,Meniscus (anatomy) ,Injury repair ,Progenitor cell ,business ,Hedgehog ,Cell biology - Published
- 2021
28. Decorin Regulates the Aggrecan Network Integrity and Biomechanical Functions of Cartilage Extracellular Matrix
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Ling Qin, Christopher Y. Li, Chao Wang, X. Lucas Lu, Qing Li, Ramin Oftadeh, Siyuan Zhou, Robert L. Mauck, Lin Han, X. Sherry Liu, Hadi Tavakoli Nia, Renato V. Iozzo, Basak Doyran, Motomi Enomoto-Iwamoto, David E. Birk, Pavan D. Patel, Biao Han, and Sheila M. Adams
- Subjects
Cartilage, Articular ,musculoskeletal diseases ,Decorin ,General Physics and Astronomy ,02 engineering and technology ,Matrix (biology) ,010402 general chemistry ,Fibril ,01 natural sciences ,Article ,Extracellular matrix ,medicine ,General Materials Science ,Aggrecans ,Aggrecan ,biology ,Chemistry ,Regeneration (biology) ,Cartilage ,General Engineering ,musculoskeletal system ,021001 nanoscience & nanotechnology ,Extracellular Matrix ,Nanostructures ,0104 chemical sciences ,Cell biology ,carbohydrates (lipids) ,medicine.anatomical_structure ,Proteoglycan ,biology.protein ,Proteoglycans ,0210 nano-technology - Abstract
Joint biomechanical functions rely on the integrity of cartilage extracellular matrix. Understanding the molecular activities that govern cartilage matrix assembly is critical for developing effective cartilage regeneration strategies. This study elucidated the role of decorin, a small leucine-rich proteoglycan, in the structure and biomechanical functions of cartilage. In decorin-null cartilage, we discovered a substantial reduction of aggrecan content, the major proteoglycan of cartilage matrix, and mild changes in collagen fibril nanostructure. This loss of aggrecan resulted in significantly impaired biomechanical properties of cartilage, including decreased modulus, elevated hydraulic permeability, and reduced energy dissipation capabilities. At the cellular level, we found that decorin functions to increase the retention of aggrecan in the neo-matrix of chondrocytes, rather than to directly influence the biosynthesis of aggrecan. At the molecular level, we demonstrated that decorin significantly increases the adhesion between aggrecan and aggrecan molecules and between aggrecan molecules and collagen II fibrils. We hypothesize that decorin plays a crucial structural role in mediating the matrix integrity and biomechanical functions of cartilage by providing physical linkages to increase the adhesion and assembly of aggrecan molecules at the nanoscale.
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- 2019
29. Poisoning exposure cases involving e-cigarettes and e-liquid in the United States, 2010–2018
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Baoguang Wang, Alexander Persoskie, and Sherry Liu
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Nicotine ,Poison Control Centers ,Adolescent ,Databases, Factual ,Injury control ,Accident prevention ,Poison control ,Electronic Nicotine Delivery Systems ,Toxicology ,Suicide prevention ,Article ,Occupational safety and health ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Environmental health ,Injury prevention ,Humans ,Medicine ,030212 general & internal medicine ,Child ,business.industry ,Poisoning ,Human factors and ergonomics ,030208 emergency & critical care medicine ,Tobacco Products ,General Medicine ,United States ,Child, Preschool ,business ,Electronic cigarette - Abstract
INTRODUCTION: Poisoning exposure cases involving e-cigarettes have increased since 2010, coinciding with increasing rates of e-cigarette use in the United States (US). Given the increasing prevalence of e-cigarette use and ever-changing product designs, particularly the development of new products with high nicotine levels, it is important to conduct ongoing surveillance of poisoning exposure cases involving e-cigarettes. The objective of this study is to describe trends and characteristics of poisoning exposure cases involving e-cigarettes and e-liquids reported to poison control centers in the US. METHODS: We analyzed e-cigarette exposure cases from the National Poison Data System (NPDS) during 2010–2018 by year and other characteristics. RESULTS: The annual number of e-cigarette exposure cases increased greatly between 2010 and 2014, reaching a peak of 3742 in 2014, and then decreasing each year between 2015 and 2017. Between 2017 and 2018, the overall number of e-cigarette exposure cases increased by 25.0% (from 2320 to 2901). Approximately two-thirds (64.8%) of all cases were in children under age five, and 14.7% were in children aged 5–17 years or young adults aged 18–24 years. A small proportion of cases developed life-threatening symptoms (0.1%); and cases with more serious medical outcomes tended to be exposed to a higher e-liquid or nicotine quantity. CONCLUSIONS: Annual declines in e-cigarette exposure cases between 2015 and 2017 did not continue in 2018. The rapid changes in the occurrence of poisoning exposure cases involving e-cigarettes coupled with the development of new tobacco products and ever-evolving tobacco use landscape underscore the importance of continued surveillance of these poisoning exposure cases. Continuous monitoring of these poisoning exposure cases may inform efforts aimed at preventing e-cigarette poisoning exposures.
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- 2019
30. Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss
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Hyunsoo Kim, Wei Yu, Yulong Wei, X. Sherry Liu, Shuying Yang, Yongwon Choi, Lutian Yao, Nathaniel A. Dyment, Ziqing Li, Xi Jiang, Wei Tong, Leilei Zhong, Tao Gui, Nicholas Holdreith, Jaimo Ahn, and Ling Qin
- Subjects
0301 basic medicine ,musculoskeletal diseases ,medicine.medical_specialty ,biology ,Chemistry ,Osteoporosis ,General Medicine ,medicine.disease ,Bone resorption ,Bone remodeling ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Endocrinology ,RANKL ,Osteoclast ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,biology.protein ,Ovariectomized rat ,Cortical bone ,Bone marrow ,Research Article - Abstract
Bone is maintained by coupled activities of bone-forming osteoblasts/osteocytes and bone-resorbing osteoclasts. Alterations in this relationship can lead to pathologic bone loss such as osteoporosis. It is well known that osteogenic cells support osteoclastogenesis via production of RANKL. Interestingly, our recently identified bone marrow mesenchymal cell population-marrow adipogenic lineage precursors (MALPs) that form a multidimensional cell network in bone-was computationally demonstrated to be the most interactive with monocyte-macrophage lineage cells through high and specific expression of several osteoclast regulatory factors, including RANKL. Using an adipocyte-specific Adipoq-Cre to label MALPs, we demonstrated that mice with RANKL deficiency in MALPs have a drastic increase in trabecular bone mass in long bones and vertebrae starting from 1 month of age, while their cortical bone appears normal. This phenotype was accompanied by diminished osteoclast number and attenuated bone formation at the trabecular bone surface. Reduced RANKL signaling in calvarial MALPs abolished osteolytic lesions after LPS injections. Furthermore, in ovariectomized mice, elevated bone resorption was partially attenuated by RANKL deficiency in MALPs. In summary, our studies identified MALPs as a critical player in controlling bone remodeling during normal bone metabolism and pathological bone loss in a RANKL-dependent fashion.
- Published
- 2021
31. Artistic Practice in Telepresence during the COVID-19 Pandemic
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Wing Ting (Jan) Sze, Rosina Yuan, Ye (Sherry) Liu, and Chun Wai (Wilson) Yeung
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History ,Coronavirus disease 2019 (COVID-19) ,Pandemic ,Media studies - Published
- 2021
32. Identification of Gli1 as a progenitor cell marker for meniscus development and injury repair
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Lutian Yao, Sun H, Yong-An Zhang, Su Jin Heo, Fanxin Long, Yuting Wei, Robert L. Mauck, Wenbao Yu, Tao Gui, Jaimo Ahn, Lin Han, Miltiadis H. Zgonis, Leilei Zhong, Xiaowei Sherry Liu, Ling Qin, and Eiki Koyama
- Subjects
education.field_of_study ,Pathology ,medicine.medical_specialty ,integumentary system ,biology ,business.industry ,Activator (genetics) ,Population ,Mesenchymal stem cell ,Osteoarthritis ,Injury repair ,musculoskeletal system ,medicine.disease ,GLI1 ,biology.protein ,Medicine ,Progenitor cell ,business ,education ,Progenitor - Abstract
Meniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using Gli1-CreER tdTomato mice, we found that Gli1+ cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1+ cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1+ cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of Gli1+ cells. Normally, the tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1+ cells further hindered this repair process. Strikingly, intra-articular injection of Gli1+ meniscal cells or an Hh activator right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.
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- 2020
33. Peak trabecular bone microstructure predicts rate of estrogen-deficiency-induced bone loss in rats
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X. Sherry Liu, Yihan Li, Rebecca Chung, Wei Ju Tseng, Hongbo Zhao, and Chantal M.J. de Bakker
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0301 basic medicine ,Peak bone mass ,medicine.medical_specialty ,Histology ,Physiology ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Ovariectomy ,Osteoporosis ,030209 endocrinology & metabolism ,Article ,Bone remodeling ,03 medical and health sciences ,0302 clinical medicine ,Trabecula ,Bone Density ,Internal medicine ,Medicine ,Animals ,Humans ,Reduction (orthopedic surgery) ,business.industry ,Estrogens ,X-Ray Microtomography ,medicine.disease ,Microstructure ,Rats ,Menopause ,Bone Diseases, Metabolic ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Estrogen ,Cancellous Bone ,Female ,business - Abstract
Postmenopausal osteoporosis affects a large number of women worldwide. Reduced estrogen levels during menopause lead to accelerated bone remodeling, resulting in low bone mass and increased fracture risk. Both peak bone mass and the rate of bone loss are important predictors of postmenopausal osteoporosis risk. However, whether peak bone mass and/or bone microstructure directly influence the rate of bone loss following menopause remains unclear. Our study aimed to establish the relationship between peak bone mass/microstructure and the rate of bone loss in response to estrogen deficiency following ovariectomy (OVX) surgery in rats of homogeneous background by tracking the skeletal changes using in vivo micro-computed tomography (μCT) and three-dimensional (3D) image registrations. Linear regression analyses demonstrated that the peak bone microstructure, but not peak bone mass, was highly predictive of the rate of OVX-induced bone loss. In particular, the baseline trabecular thickness was found to have the highest correlation with the degree of OVX-induced bone loss and trabecular stiffness reduction. Given the same bone mass, the rats with thicker baseline trabeculae had a lower rate of trabecular microstructure and stiffness deterioration after OVX. Moreover, further evaluation to track the changes within each individual trabecula via our novel individual trabecular dynamics (ITD) analysis suggested that a trabecular network with thicker trabeculae is less likely to disconnect or perforate in response to estrogen deficiency, resulting a lower degree of bone loss. Taken together, these findings indicate that the rate of estrogen-deficiency-induced bone loss could be predicted by peak bone microstructure, most notably the trabecular thickness. Given the same bone mass, a trabecular bone phenotype with thin trabeculae may be a risk factor toward accelerated postmenopausal bone loss.
- Published
- 2020
34. Bone marrow adipogenic lineage precursors (MALPs) promote osteoclastogenesis in bone remodeling and pathologic bone loss
- Author
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Leilei Zhong, Wei Yu, Nathaniel A. Dyment, Tao Gui, Hyunsoo Kim, Xiaowei Sherry Liu, Lutian Yao, Yongwon Choi, Ziqing Li, Ling Qin, Jaimo Ahn, Yulong Wei, and Shuying Yang
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,biology ,Chemistry ,Osteoporosis ,medicine.disease ,Bone resorption ,Bone remodeling ,medicine.anatomical_structure ,Endocrinology ,Osteoclast ,RANKL ,Internal medicine ,medicine ,Ovariectomized rat ,biology.protein ,Cortical bone ,Bone marrow - Abstract
Bone is maintained by coupled activities of bone-forming osteoblasts/osteocytes and bone-resorbing osteoclasts and an alternation of this relationship can lead to pathologic bone loss such as in osteoporosis. It is well known that osteogenic cells support osteoclastogenesis via synthesizing RANKL. Interestingly, our recently identified bone marrow mesenchymal cell population—marrow adipogenic lineage precursors (MALPs) that form a multi-dimensional cell network in bone—was computationally demonstrated to be the most interactive with monocyte-macrophage lineage cells through highly and specifically expressing several osteoclast regulatory factors, including RANKL. Using an adipocyte-specific Adipoq-Cre to label MALPs, we demonstrated that mice with RANKL deficiency in MALPs have a drastic increase of trabecular bone mass in long bones and vertebrae starting from 1 month of age but that their cortical bone is normal. This phenotype was accompanied by diminished osteoclast number and attenuated bone formation at the trabecular bone surface. Reduced RANKL signaling in calvarial MALPs also abolished osteolytic lesions after lipopolysaccharide (LPS) injections. Furthermore, in ovariectomized mice, elevated bone resorption was partially attenuated by RANKL deficiency in MALPs. In summary, our studies identified MALPs as a critical player in controlling bone remodeling during normal bone metabolism and pathological bone loss in a RANKL-dependent fashion.
- Published
- 2020
35. Pregnancy and Lactation Impair Subchondral Bone Leading to Reduced Rat Supraspinatus Tendon-to-Bone Insertion Site Failure Properties
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Snehal S. Shetye, Yilu Zhou, Yihan Li, Ashley K. Fung, X. Sherry Liu, and Louis J. Soslowsky
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Biomedical Engineering ,Joint laxity ,Tendons ,03 medical and health sciences ,Rotator Cuff ,0302 clinical medicine ,Pregnancy ,Tendon Injuries ,Physiology (medical) ,Internal medicine ,Lactation ,medicine ,Animals ,Rotator cuff ,Humerus ,030222 orthopedics ,business.industry ,030229 sport sciences ,medicine.disease ,musculoskeletal system ,Research Papers ,Tendon ,Rats ,medicine.anatomical_structure ,Endocrinology ,Epiphysis ,Orthopedic surgery ,Female ,business - Abstract
Pregnant women experience weight gain, gait changes, and biochemical fluctuations that impair joint function and alter the maternal skeleton. Hormonal changes increase pelvic ligament laxity in preparation for childbirth and affect peripheral joint laxity. Calcium demands also rise during pregnancy and lactation, resulting in reduced bone mineral density (BMD) and maternal bone loss. Altered tendon properties and bone loss during pregnancy and lactation may impact tendon insertion sites, such as rotator cuff tendons where insertion site ruptures are common. However, the effects of pregnancy and lactation at the tendon-to-bone interface have not been investigated. Therefore, the objective of this study was to evaluate supraspinatus tendon mechanical properties and insertion site microstructure during pregnancy, lactation, and postweaning recovery in female rats. We hypothesized that pregnancy and lactation would compromise supraspinatus tendon mechanical properties and subchondral bone microstructure. Female rats were divided into virgin, pregnancy, lactation, and recovery groups, and supraspinatus tendons were mechanically evaluated. Surprisingly, tendon mechanics was unaffected by pregnancy and lactation. However, tendon modulus decreased two-weeks postweaning. Additionally, tendons failed by bony avulsion at the insertion site, and the lactation group exhibited reduced failure properties corresponding to decreased subchondral bone mineralization. Lactation also resulted in dramatic bone loss at the epiphysis, but trabecular bone microarchitecture recovered postweaning. In conclusion, lactation following pregnancy impaired trabecular bone microstructure and subchondral bone mineralization, leading to reduced supraspinatus tendon-to-bone insertion site failure properties. These findings will contribute toward understanding the pathogenesis of tendon-to-bone disorders.
- Published
- 2020
36. Infected macrophages engage alveolar epithelium to metabolically reprogram myeloid cells and promote antibacterial inflammation
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Alicia M. Holmgren, Sunny Shin, Mark A. Boyer, and Xiaowei Sherry Liu
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0303 health sciences ,medicine.medical_treatment ,Alveolar Epithelium ,Inflammation ,Translation (biology) ,Biology ,respiratory system ,biology.organism_classification ,Legionella pneumophila ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cytokine ,Immunology ,medicine ,Bystander effect ,Macrophage ,medicine.symptom ,030304 developmental biology ,030215 immunology - Abstract
Alveolar macrophages are the primary immune cells that first detect lung infection. However, only one macrophage patrols every three alveoli. How this limited number of macrophages provides protection is unclear, as numerous pathogens block cell-intrinsic immune responses. The intracellular pathogenLegionella pneumophilainhibits host translation, thereby impairing the ability of infected macrophages to produce critical cytokines. Nevertheless, infected macrophages induce an IL-1-dependent inflammatory response by recruited myeloid cells that controls infection. Here, we show that collaboration with the alveolar epithelium is critical, in that IL-1 instructs the alveolar epithelium to produce GM-CSF. Intriguingly, GM-CSF drives maximal cytokine production in bystander myeloid cells by enhancing PRR-induced glycolysis. Our findings reveal that alveolar macrophages engage alveolar epithelial signals to metabolically reprogram myeloid cells and amplify antibacterial inflammation.One Sentence SummaryThe alveolar epithelium is a central signal relay between infected and bystander myeloid cells that orchestrates antibacterial defense.
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- 2020
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37. The importance of diversity, equity, and inclusion in orthopedic research
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Robin M. Queen, Deana Mercer, Karl J. Lewis, James C. Iatridis, Brenda Frederick, Kharma C. Foucher, Clare M. Rimnac, Christopher J. Hernandez, Jennifer J. Westendorf, Marjolein C. H. van der Meulen, Tamara Alliston, X. Sherry Liu, Kenneth M. Kozloff, and Ruth Ochia
- Subjects
medicine.medical_specialty ,Equity (economics) ,Biomedical Research ,Orthopedics ,Public economics ,Orthopedic surgery ,MEDLINE ,medicine ,Orthopedics and Sports Medicine ,Cultural Diversity ,Psychology ,Societies, Medical - Published
- 2020
38. Trabecular Bone Deficit and Enhanced Anabolic Response to Re-Ambulation after Disuse in Perlecan-Deficient Skeleton
- Author
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Hongbo Zhao, Shaopeng Pei, X. Lucas Lu, Jerahme R. Martinez, Ashutosh Parajuli, Mary C. Farach-Carson, Liyun Wang, Catherine B. Kirn-Safran, and X. Sherry Liu
- Subjects
Male ,0301 basic medicine ,Osteoporosis ,lcsh:QR1-502 ,Osteoclasts ,Walking ,Mechanotransduction, Cellular ,Biochemistry ,lcsh:Microbiology ,Extracellular matrix ,Mice ,0302 clinical medicine ,Osteogenesis ,Risk Factors ,Femur ,micro-computed tomography ,biology ,Chemistry ,Phenotype ,medicine.anatomical_structure ,trabecular bone ,Cancellous Bone ,hindlimb suspension ,medicine.medical_specialty ,schwartz-jampel syndrome ,Schwartz–Jampel syndrome ,030209 endocrinology & metabolism ,Perlecan ,Osteocytes ,Article ,03 medical and health sciences ,Osteoclast ,Internal medicine ,medicine ,Animals ,Kyphosis ,Molecular Biology ,Endochondral ossification ,osteoclastogenesis ,Basement membrane ,re-ambulation ,X-Ray Microtomography ,Hematopoietic Stem Cells ,medicine.disease ,osteoporosis ,Mice, Inbred C57BL ,perlecan ,Metabolism ,030104 developmental biology ,Endocrinology ,biology.protein ,Cortical bone ,Stress, Mechanical ,Heparan Sulfate Proteoglycans - Abstract
Perlecan/Hspg2, a large monomeric heparan sulfate proteoglycan, is found in the basement membrane and extracellular matrix, where it acts as a matrix scaffold, growth factor depot, and tissue barrier. Perlecan deficiency leads to skeletal dysplasia in Schwartz-Jampel Syndrome (SJS) and is a risk factor for osteoporosis. In the SJS-mimicking murine model (Hypo), inferior cortical bone quality and impaired mechanotransduction in osteocytes were reported. This study focused on trabecular bone, where perlecan deficiency was hypothesized to result in structural deficit and altered response to disuse and re-loading. We compared the Hypo versus WT trabecular bone in both axial and appendicular skeletons of 8-38-week-old male mice, and observed severe trabecular deficit in Hypo mice, approximately 50% reduction of Tb.BV/TV regardless of skeletal site and animal age. Defects in endochondral ossification (e.g., accelerated mineralization), increases in osteoclast activity, and altered differentiation of bone progenitor cells in marrow contributed to the Hypo phenotype. The Hypo trabecular bone deteriorated further under three-week hindlimb suspension as did the WT. Re-ambulation partially recovered the lost trabecular bone in Hypo, but not in WT mice. The novel finding that low-impact loading could counter detrimental disuse effects in the perlecan-deficient skeleton suggests a strategy to maintain skeletal health in SJS patients.
- Published
- 2020
39. Structural role of osteocyte lacunae on mechanical properties of bone matrix: A cohesive finite element study
- Author
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Wen Sang, Jane Guignon, Ani Ural, X. Sherry Liu, and Yihan Li
- Subjects
Materials science ,Finite Element Analysis ,Biomedical Engineering ,Bone Matrix ,Fracture mechanics ,Bone fracture ,medicine.disease ,Bone tissue ,Osteocytes ,Article ,Rats ,Biomaterials ,medicine.anatomical_structure ,Mechanics of Materials ,Elastic Modulus ,Osteocyte ,Ultimate tensile strength ,medicine ,Fracture (geology) ,Animals ,Female ,Composite material ,Porosity ,Elastic modulus ,Stress concentration - Abstract
Despite the extensive studies on biological function of osteocytes, there are limited studies that evaluated the structural role of osteocyte lacunae on local mechanical properties of the bone matrix. As a result, the goal of this study was to elucidate the independent contribution of osteocyte lacunae structure on mechanical properties and fracture behavior of the bone matrix uncoupled from its biological effects and bone tissue composition variation. This study combined cohesive finite element modeling with experimental data from a lactation rat model to evaluate the influence of osteocyte lacunar area porosity, density, size, axis ratio, and orientation on the elastic modulus, ultimate strength, and ultimate strain of the bone matrix as well as on local crack formation and propagation. It also performed a parametric study to isolate the influence of a single osteocyte lacunae structural property on the mechanical properties of the bone matrix. The experimental measurements demonstrated statistically significant differences in lacunar size between ovariectomized rats with lactation history and virgin groups (both ovariectomized and intact) and in axis ratio between rats with lactation history and virgins. There were no differences in mechanical properties between virgin and lactation groups as determined by the finite element simulations. However, there were statistically significant linear relationships between the physiological range of osteocyte lacunar area porosity, density, size, and orientation and the elastic modulus and ultimate strength of the bone matrix in virgin and lactation rats. The parametric study also revealed similar but stronger relationships between elastic modulus and ultimate strength and lacunar density, size, and orientation. The simulations also demonstrated that the osteocyte lacunae guided the crack propagation through local stress concentrations. In summary, this study enhanced the limited knowledge on the structural role of osteocyte lacunae on local mechanical properties of the bone matrix. These data are important in gaining a better understanding of the mechanical implications of the local modifications due to osteocytes in the bone matrix.
- Published
- 2022
40. Structural Adaptations in the Rat Tibia Bone Induced by Pregnancy and Lactation Confer Protective Effects Against Future Estrogen Deficiency
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Chantal M.J. de Bakker, X. Sherry Liu, Ling Qin, Wei Tong, Tiao Lin, Laurel Leavitt, Yihan Li, Hongbo Zhao, and Wei Ju Tseng
- Subjects
0301 basic medicine ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Population ,030209 endocrinology & metabolism ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Internal medicine ,Lactation ,medicine ,Orthopedics and Sports Medicine ,education ,Bone mineral ,Pregnancy ,education.field_of_study ,business.industry ,medicine.disease ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Estrogen ,Cortical bone ,business - Abstract
The female skeleton undergoes substantial structural changes during the course of reproduction. Although bone mineral density recovers postweaning, reproduction may induce permanent alterations in maternal bone microarchitecture. However, epidemiological studies suggest that a history of pregnancy and/or lactation does not increase the risk of postmenopausal osteoporosis or fracture and may even have a protective effect. Our study aimed to explain this paradox by using a rat model, combined with in vivo micro-computed tomography (μCT) imaging and bone histomorphometry, to track the changes in bone structure and cellular activities in response to estrogen deficiency following ovariectomy (OVX) in rats with and without a reproductive history. Our results demonstrated that a history of reproduction results in an altered skeletal response to estrogen-deficiency-induced bone loss later in life. Prior to OVX, rats with a reproductive history had lower trabecular bone mass, altered trabecular microarchitecture, and more robust cortical structure at the proximal tibia when compared to virgins. After OVX, these rats underwent a lower rate of trabecular bone loss than virgins, with minimal structural deterioration. As a result, by 12 weeks post-OVX, rats with a reproductive history had similar trabecular bone mass, elevated trabecular thickness, and increased robustness of cortical bone when compared to virgins, resulting in greater bone stiffness. Further evaluation suggested that reproductive-history-induced differences in post-OVX trabecular bone loss were likely due to differences in baseline trabecular microarchitecture, particularly trabecular thickness. Rats with a reproductive history had a larger population of thick trabeculae, which may be protective against post-OVX trabecular connectivity deterioration and bone loss. Taken together, these findings indicate that reproduction-associated changes in bone microarchitecture appear to reduce the rate of bone loss induced by estrogen deficiency later in life, and thereby exert a long-term protective effect on bone strength. © 2018 American Society for Bone and Mineral Research.
- Published
- 2018
41. Effects of reproduction on sexual dimorphisms in rat bone mechanics
- Author
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Liu Yang, Wei Ju Tseng, Yihan Li, X. Sherry Liu, Laurel Leavitt, Chantal M.J. de Bakker, Hongbo Zhao, and Allison R. Altman-Singles
- Subjects
Male ,0301 basic medicine ,Peak bone mass ,Osteoporosis ,Biomedical Engineering ,Biophysics ,Physiology ,030209 endocrinology & metabolism ,Bone and Bones ,Article ,Bone remodeling ,03 medical and health sciences ,0302 clinical medicine ,Bone Density ,Pregnancy ,Lactation ,medicine ,Animals ,Orthopedics and Sports Medicine ,Mechanical Phenomena ,Sex Characteristics ,business.industry ,Reproduction ,Rehabilitation ,medicine.disease ,Biomechanical Phenomena ,Rats ,Sexual dimorphism ,Menopause ,030104 developmental biology ,medicine.anatomical_structure ,Female ,Cortical bone ,Bone Remodeling ,business - Abstract
Osteoporosis most commonly affects postmenopausal women. Although men are also affected, women over 65 are 6 times more likely to develop osteoporosis than men of the same age. This is largely due to accelerated bone remodeling after menopause; however, the peak bone mass attained during young adulthood also plays an important role in osteoporosis risk. Multiple studies have demonstrated sexual dimorphisms in peak bone mass, and additionally, the female skeleton is significantly altered during pregnancy/lactation. Although clinical studies suggest that a reproductive history does not increase the risk of developing postmenopausal osteoporosis, reproduction has been shown to induce long-lasting alterations in maternal bone structure and mechanics, and the effects of pregnancy and lactation on maternal peak bone quality are not well understood. This study compared the structural and mechanical properties of male, virgin female, and post-reproductive female rat bone at multiple skeletal sites and at three different ages. We found that virgin females had a larger quantity of trabecular bone with greater trabecular number and more plate-like morphology, and, relative to their body weight, had a greater cortical bone size and greater bone strength than males. Post-reproductive females had altered trabecular microarchitecture relative to virgins, which was highly similar to that of male rats, and showed similar cortical bone size and bone mechanics to virgin females. This suggests that, to compensate for future reproductive bone losses, females may start off with more trabecular bone than is mechanically necessary, which may explain the paradox that reproduction induces long-lasting changes in maternal bone without increasing postmenopausal fracture risk.
- Published
- 2018
42. Mechanical Regulation of the Maternal Skeleton during Reproduction and Lactation
- Author
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Chantal M J de Bakker, X. Sherry Liu, Xiaohan Lai, and Liyun Wang
- Subjects
0301 basic medicine ,Bone density ,Anabolism ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Weaning ,Biology ,Maternal Physiology ,Osteocytes ,Bone and Bones ,Article ,Weight-Bearing ,03 medical and health sciences ,0302 clinical medicine ,Bone Density ,Pregnancy ,Lactation ,medicine ,Cortical Bone ,Animals ,Humans ,Skeleton (computer programming) ,Adaptation, Physiological ,Cell biology ,Biomechanical Phenomena ,030104 developmental biology ,medicine.anatomical_structure ,Osteocyte ,Cancellous Bone ,Cortical bone ,Calcium ,Female ,Animal studies ,Bone Remodeling - Abstract
PURPOSE OF REVIEW: This review summarizes recently published data on the effects of pregnancy and lactation on bone structure, mechanical properties, and mechano-responsiveness in an effort to elucidate how the balance between the structural and metabolic functions of the skeleton is achieved during these physiological processes. RECENT FINDINGS: While pregnancy and lactation induce significant changes in bone density and structure to provide calcium for fetal/infant growth, the maternal physiology also comprises several innate compensatory mechanisms that allow for the maintenance of skeletal mechanical integrity. Both clinical and animal studies suggest that pregnancy and lactation lead to adaptations in cortical bone structure to allow for rapid calcium release from the trabecular compartment while maintaining whole-bone stiffness and strength. Moreover, extents of lactation-induced bone loss and weaning-induced recovery are highly dependent on a given bone’s load-bearing function, resulting in better protection of the mechanical integrity at critical load-bearing sites. The recent discovery of lactation-induced osteocytic peri-lacunar/canalicular remodeling (PLR) indicates a new means for osteocytes to modulate mineral homeostasis and tissue-level mechanical properties of the maternal skeleton. Furthermore, lactation-induced PLR may also play an important role in maintaining the maternal skeleton’s load-bearing capacity by altering osteocyte’s microenvironment and modulating the transmission of anabolic mechanical signals to osteocytes. SUMMARY: Both clinical and animal studies show that parity and lactation have no adverse, or a positive effect on bone strength later in life. The skeletal effects during pregnancy and lactation reflect an optimized balance between the mechanical and metabolic functions of the skeleton.
- Published
- 2019
43. Maternal bone adaptation to mechanical loading during pregnancy, lactation, and post-weaning recovery
- Author
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Rebecca Chung, Tan Meng, Wei Ju Tseng, Liyun Wang, Shaopeng Pei, Chantal M.J. de Bakker, Xiaohan Lai, X. Sherry Liu, Ashutosh Parajuli, Hongbo Zhao, and Yihan Li
- Subjects
0301 basic medicine ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Stimulation ,Physical exercise ,Weaning ,Osteocytes ,Article ,Bone and Bones ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Interstitial fluid ,Lactation ,Cortical Bone ,medicine ,Animals ,business.industry ,medicine.disease ,Skeleton (computer programming) ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Osteocyte ,Female ,Cortical bone ,business - Abstract
The maternal skeleton undergoes dramatic bone loss during pregnancy and lactation, and substantial bone recovery post-weaning. The structural adaptations of maternal bone during reproduction and lactation exert a better protection of the mechanical integrity at the critical load-bearing sites, suggesting the importance of physiological load-bearing in regulating reproduction-induced skeletal alterations. Although it is suggested that physical exercise during pregnancy and breastfeeding improves women's physical and psychological well-being, its effects on maternal bone health remain unclear. Therefore, the objective of this study was to investigate the maternal bone adaptations to external mechanical loading during pregnancy, lactation, and post-weaning recovery. By utilizing an in vivo dynamic tibial loading protocol in a rat model, we demonstrated improved maternal cortical bone structure in response to dynamic loading at tibial midshaft, regardless of reproductive status. Notably, despite the minimal loading responses detected in the trabecular bone in virgins, rat bone during lactation experienced enhanced mechano-responsiveness in both trabecular and cortical bone compartments when compared to rats at other reproductive stages or age-matched virgins. Furthermore, our study showed that the lactation-induced elevation in osteocyte peri-lacunar/canalicular remodeling (PLR) activities led to enlarged osteocyte lacunae. This may result in alterations in interstitial fluid flow-mediated mechanical stimulation on osteocytes and an elevation in solute transport through the lacunar-canalicular system (LCS) during high-frequency dynamic loading, thus enhancing mechano-responsiveness of maternal bone during lactation. Taken together, findings from this study provide important insights into the relationship between reproduction- and lactation-induced skeletal changes and external mechanical loading, emphasizing the importance of weight-bearing exercise on maternal bone health during reproduction and postpartum.
- Published
- 2021
44. Lactation alters fluid flow and solute transport in maternal skeleton: A multiscale modeling study on the effects of microstructural changes and loading frequency
- Author
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Yihan Li, Liyun Wang, Xiaohan Lai, Xiaowei Sherry Liu, and Rebecca Chung
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0301 basic medicine ,Cell signaling ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,Poromechanics ,030209 endocrinology & metabolism ,Matrix (biology) ,Bone canaliculus ,Osteocytes ,Bone and Bones ,Article ,Cell membrane ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Lactation ,Tibia ,Chemistry ,Skeleton (computer programming) ,Multiscale modeling ,030104 developmental biology ,medicine.anatomical_structure ,Osteocyte ,Biophysics ,Female ,Porosity - Abstract
The female skeleton undergoes significant material and ultrastructural changes to meet high calcium demands during reproduction and lactation. Through the peri-lacunar/canalicular remodeling (PLR), osteocytes actively resorb surrounding matrix and enlarge their lacunae and canaliculi during lactation, which are quickly reversed after weaning. How these changes alter the physicochemical environment of osteocytes, the most abundant and primary mechanosensing cells in bone, are not well understood. In this study, we developed a multiscale poroelastic modeling technique to investigate lactation-induced changes in stress, fluid pressurization, fluid flow, and solute transport across multiple length scales (whole bone, porous midshaft cortex, lacunar-canalicular pore system (LCS), and pericellular matrix (PCM) around osteocytes) in murine tibiae subjected to axial compression at 3 N peak load (~320 μe) at 0.5, 2, or 4 Hz. Based on previously reported skeletal anatomical measurements from lactating and nulliparous mice, our models demonstrated that loading frequency, LCS porosity, and PCM density were major determinants of fluid and solute flows responsible for osteocyte mechanosensing, cell-cell signaling, and metabolism. When loaded at 0.5 Hz, lactation-induced LCS expansion and potential PCM reduction promoted solute transport and osteocyte mechanosensing via primary cilia, but suppressed mechanosensing via fluid shear and/or drag force on the cell membrane. Interestingly, loading at 2 or 4 Hz was found to overcome the mechanosensing deficits observed at 0.5 Hz and these counter effects became more pronounced at 4 Hz and with sparser PCM in the lactating bone. Synergistically, higher loading frequency (2, 4 Hz) and sparser PCM enhanced flow-mediated mechanosensing and diffusion/convection of nutrients and signaling molecules for osteocytes. In summary, lactation-induced structural changes alter the local environment of osteocytes in ways that favor metabolism, mechanosensing, and post-weaning recovery of maternal bone. Thus, osteocytes play a role in balancing the metabolic and mechanical functions of female skeleton during reproduction and lactation.
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- 2021
45. Activation, development, and attenuation of modeling- and remodeling-based bone formation in adult rats
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Xi Jiang, Wei Ju Tseng, Wenzheng Wang, Shaopeng Pei, Nathaniel A. Dyment, Tala Azar, Hongbo Zhao, and X. Sherry Liu
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Male ,medicine.medical_specialty ,Ovariectomy ,Osteoporosis ,Biophysics ,Parathyroid hormone ,Bioengineering ,Bone and Bones ,Article ,Bone resorption ,Anabolic Agents ,Biomaterials ,Bone Density ,Osteogenesis ,Internal medicine ,medicine ,Animals ,Bone formation ,Ovariectomized female ,Tibia ,Chemistry ,medicine.disease ,Rats ,Trabecular bone ,Endocrinology ,Parathyroid Hormone ,Mechanics of Materials ,Ceramics and Composites ,Female ,Homeostasis ,circulatory and respiratory physiology - Abstract
Activation of modeling-based bone formation (MBF - bone formation without prior activation of bone resorption), has been identified as an important mechanism by which anabolic agents, such as intermittent parathyroid hormone (PTH), rapidly elicit new bone formation. Using a novel cryohistology imaging platform, coupled with sequential multicolor fluorochrome injections, we demonstrated that MBF and remodeling-based bone formation (RBF) in the adult rat tibia model have similar contributions to trabecular bone homeostasis. PTH treatment resulted in a 2.4–4.9 fold greater bone formation rate over bone surface (BFR/BS) by RBF and a 4.3–8.5 fold greater BFR/BS by MBF in male, intact female, and ovariectomized female rats. Moreover, regardless of bone formation type, once a formation site is activated by PTH, mineral deposition continues throughout the entire treatment duration. Furthermore, by tracking the sequence of multicolor fluorochrome labels, we discovered that MBF, a highly efficient but often overlooked regenerative mechanism, is activated more rapidly but attenuated faster than RBF in response to PTH. This suggests that MBF and RBF contribute differently to PTH’s anabolic effect in rats: MBF has a greater contribution to the acute elevation in bone mass at the early stage of treatment while RBF contributes to the sustained treatment effect.
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- 2021
46. Pregnancy and Lactation Impair Subchondral Bone Leading to Reduced Rat Supraspinatus Tendon-to-Bone Insertion Site Failure Properties
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Fung, Ashley K., primary, Shetye, Snehal S., additional, Li, Yihan, additional, Zhou, Yilu, additional, Sherry Liu, X., additional, and Soslowsky, Louis J., additional
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- 2020
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47. Type III collagen is a key regulator of the collagen fibrillar structure and biomechanics of articular cartilage and meniscus
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Wang, Chao, primary, Brisson, Becky K., additional, Terajima, Masahiko, additional, Li, Qing, additional, Hoxha, Kevt’her, additional, Han, Biao, additional, Goldberg, Abby M., additional, Sherry Liu, X., additional, Marcolongo, Michele S., additional, Enomoto-Iwamoto, Motomi, additional, Yamauchi, Mitsuo, additional, Volk, Susan W., additional, and Han, Lin, additional
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- 2020
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48. Efficient 3D rigid-body registration of micro-MR and micro-CT trabecular bone images.
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Chamith S. Rajapakse, Jeremy F. Magland, Suzanne L. Wehrli, Henry Zhang, X. Sherry Liu, X. Edward Guo, and Felix W. Wehrli
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- 2008
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49. Systematic review: Can non-mydriatic cameras accurately detect diabetic retinopathy?
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Lauren Griffith, Chloe Bedard, Hertzel C. Gerstein, Christopher Patterson, and Siying Sherry Liu
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Adult ,Male ,Endocrinology, Diabetes and Metabolism ,Population ,Adult population ,MEDLINE ,030209 endocrinology & metabolism ,Retina ,Food and drug administration ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Diabetes mellitus ,Photography ,Internal Medicine ,Pupillary response ,medicine ,Humans ,education ,education.field_of_study ,Diabetic Retinopathy ,business.industry ,Reproducibility of Results ,General Medicine ,Diabetic retinopathy ,Middle Aged ,Retinal photography ,medicine.disease ,030221 ophthalmology & optometry ,Optometry ,Female ,business - Abstract
Aims Diabetes puts many individuals at risk for developing diabetic retinopathy (DR). Non-mydriatic (NM) retinal photography without pharmacological pupil dilation can be used to detect DR, however, its value in a general clinical setting has not been established. The objective of this review is to evaluate the validity of NM retinal photos, as compared to the reference standard of seven standard stereoscopic 30 degree field photographs (7SF), for their use of detecting DR in community-dwelling adults. Methods English articles were identified through MEDLINE (1992–2016), EMBASE (1992–2016), Center for Disease Control and Prevention, Food and Drug Administration, Health Canada, and Google Scholar (1992–2016). Only studies that examined the validity of NM retinal photos, without pharmacological pupil dilation, as compared to 7SF, used in a community-dwelling adult population were included. Risk of bias was assessed using the QUADAS-2. Results Of the 368 articles identified in the search, 6 articles met eligibility requirements. Sensitivities ranged from 64 to 97.9% and specificities ranged from 65.6 to 98%. Studies that used multiple field images to detect DR in a younger population generally produced higher quality photos and more valid results. Conclusions The strongest validity indicators were reported in studies capturing multiple field images.
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- 2017
50. Intermittent Parathyroid Hormone After Prolonged Alendronate Treatment Induces Substantial New Bone Formation and Increases Bone Tissue Heterogeneity in Ovariectomized Rats
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Allison R. Altman-Singles, Ling Qin, Wei Ju Tseng, Chantal M.J. de Bakker, Do-Gyoon Kim, X. Sherry Liu, Juhanna Robberts, Carina Lott, Lin Han, Hongbo Zhao, and Yong-Hoon Jeong
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0301 basic medicine ,medicine.medical_specialty ,Ovariectomy ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Parathyroid hormone ,030209 endocrinology & metabolism ,Bone tissue ,Article ,Bone resorption ,Bone remodeling ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Osteogenesis ,In vivo ,Internal medicine ,medicine ,Animals ,Humans ,Orthopedics and Sports Medicine ,Osteoporosis, Postmenopausal ,Alendronate ,Chemistry ,X-Ray Microtomography ,Bisphosphonate ,Rats ,Resorption ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Parathyroid Hormone ,Ovariectomized rat ,Female - Abstract
Postmenopausal osteoporosis is often treated with bisphosphonates (eg, alendronate, [ALN]), but oversuppression of bone turnover by long-term bisphosphonate treatment may decrease bone tissue heterogeneity. Thus, alternate treatment strategies after long-term bisphosphonates are of great clinical interest. The objective of the current study was to determine the effect of intermittent parathyroid hormone (PTH) following 12 weeks of ALN (a bisphosphonate) treatment in 6-month-old, ovariectomized (OVX) rats on bone microarchitecture, bone remodeling dynamics, and bone mechanical properties at multiple length scales. By using in vivo μCT and 3D in vivo dynamic bone histomorphometry techniques, we demonstrated the efficacy of PTH following ALN therapy for stimulating new bone formation, and increasing trabecular thickness and bone volume fraction. In healthy bone, resorption and formation are coupled and balanced to sustain bone mass. OVX results in resorption outpacing formation, and subsequent bone loss and reduction in bone tissue modulus and tissue heterogeneity. We showed that ALN treatment effectively reduced bone resorption activity and regained the balance with bone formation, preventing additional bone loss. However, ALN treatment also resulted in significant reductions in the heterogeneity of bone tissue mineral density and tissue modulus. On the other hand, PTH treatment was able to shift the bone remodeling balance in favor of formation, with or without a prior treatment with ALN. Moreover, by altering the tissue mineralization, PTH alleviated the reduction in heterogeneity of tissue material properties induced by prolonged ALN treatment. Furthermore, switching to PTH treatment from ALN improved bone's postyield mechanical properties at both the whole bone and apparent level compared to ALN alone. The current findings suggest that intermittent PTH treatment should be considered as a viable treatment option for patients with prior treatment with bisphosphonates. © 2017 American Society for Bone and Mineral Research.
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- 2017
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