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Injectable hydrogels have been considered as promising materials for bone regeneration, but their osteoinduction and mechanical performance are yet to be improved. In this study, a novel biocompatible injectable and self-healing nano hybrid hydrogel was on-demand prepared via a fast (within 30 s) and easy gelation approach by reversible Schiff base formed between −CH=O of oxidized sodium alginate (OSA) and −NH2 of glycol chitosan (GCS) mixed with calcium phosphate nanoparticles (CaP NPs). Its raw materials can be ready in large quantities by a simple synthesis process. The mechanical strength, degradation and swelling behavior of the hydrogel can be readily controlled by simply controlling the molar ratio of −CH=O and −NH2. This hydrogel exhibits pH responsiveness, good degradability and biocompatibility. The hydrogel used as the matrix for mesenchymal stem cells can significantly induce the proliferation, differentiation and osteoinduction in vitro. These results showed this novel hydrogel is an ideal candidate for applications in bone tissue regeneration and drug delivery.

Osteoporosis is a bone metabolic disease caused by the imbalance between osteoblasts and osteoclasts due to excess osteoclastogenesis, manifesting in the decrease of bone density and bone strength. Scutellariae Radix shows good anti-osteoporosis activity, but the effective component is still unclear. Cell membrane chromatography (CMC) is a biological affinity chromatography with membrane immobilized on a silica carrier as the stationary phase. It can realize a dynamical simulation of interactions between drugs and receptors on cell membrane, which is suitable for screening active compounds from complex systems. In this study, the components of Scutellariae Radix with potential anti-osteoporosis activity through inhibiting the differentiation from bone marrow mononuclear cells (BMMCs) to osteoclast were screened by a BMMC/CMC analytical system. Firstly, a new 3-mercaptopropyltrimethoxysilane (MPTS)-modified BMMC/CMC stationary phase was developed to realize covalent binding with cell membrane fractions. By investigating the retention time (tR) of the positive drug, the life span of the MPTS-modified CMC columns was significantly improved from 3 to 12 days. Secondly, 6 components of Scutellariae Radix were screened to show affinity to membrane receptors on BMMCs by a two-dimensional BMMC/CMC–TOFMS analytical system. Among them, tectochrysin demonstrated the best anti-osteoporosis effect in vitro, which has never been reported. We found that tectochrysin could inhibit the differentiation of BMMCs into osteoclasts induced by receptor activator of nuclear factor-κΒ ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in a concentration-dependent manner in vitro. In vivo, it significantly reduced the loss of bone trabeculae in ovariectomized mice, and decreased the level of C-terminal cross-linking telopeptides of type 1 collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRAP-5b), interleukin 6 (IL-6) in serum. In conclusion, tectochrysin serves as a potential candidate in the treatment of osteoporosis. The proposed two-dimensional MPTS-modified BMMC/CMC-TOFMS analytical system shows the advantages of long-life span and fast recognition ability, which is very suitable for infrequent cell lines., Graphical abstract To screen anti-osteoporosis components from Scutellariae Radix, 2D BMMC/CMC-TOFMS analytical system was established and the column life span was significantly prolonged by MPTS modification on silica stationary phase. Tectochrysin was screened out with good anti-osteoporosis activity for the first time.Image 1

Bone loss (osteopenia) is a common complication in human solid tumour. In addition, after surgical treatment of gynaecological tumour, osteoporosis often occurs due to the withdrawal of oestrogen. The major characteristic of osteoporosis is the low bone mass with micro‐architectural deteriorated bone tissue. And the main cause is the overactivation of osteoclastogenesis, which is one of the most important therapeutic targets. Inflammation could induce the interaction of RANKL/RANK, which is the promoter of osteoclastogenesis. Triptolide is derived from the traditional Chinese herb lei gong teng, presented multiple biological effects, including anti‐cancer, anti‐inflammation and immunosuppression. We hypothesized that triptolide could inhibits osteoclastogenesis by suppressing inflammation activation. In this study, we confirmed that triptolide could suppress RANKL‐induced osteoclastogenesis in bone marrow mononuclear cells (BMMCs) and RAW264.7 cells and inhibited the osteoclast bone resorption functions. PI3K‐AKT‐NFATc1 pathway is one of the most important downstream pathways of RANKL‐induced osteogenesis. The experiments in vitro indicated that triptolide suppresses the activation of PI3K‐AKT‐NFATc1 pathway and the target point located at the upstream of AKT because both NFATc1 overexpression and AKT phosphorylation could ameliorate the triptolide suppression effects. The expression of MDM2 was elevated, which demonstrated the MDM‐p53‐induced cell death might contribute to the osteoclastogenesis suppression. Ovariectomy‐induced bone loss and inflammation activation were also found to be ameliorated in the experiments in vivo. In summary, the new effect of anti‐cancer drug triptolide was demonstrated to be anti‐osteoclastogenesis, and we demonstrated triptolide might be a promising therapy for bone loss caused by tumour.

Angelica sinensis (AS; Dang Gui), a traditional Chinese herb, has for centuries been used for the treatment of bone diseases, including osteoporosis and osteonecrosis. However, the effective ingredient and underlying mechanisms remain elusive. Here, we identified guaiacol as the active component of AS by two‐dimensional cell membrane chromatography/C18 column/time‐of‐flight mass spectrometry (2D CMC/C18 column/TOFMS). Guaiacol suppressed osteoclastogenesis and osteoclast function in bone marrow monocytes (BMMCs) and RAW264.7 cells in vitro in a dose‐dependent manner. Co‐immunoprecipitation indicated that guaiacol blocked RANK‐TRAF6 association and RANK‐C‐Src association. Moreover, guaiacol prevented phosphorylation of p65, p50, IκB (NF‐κB pathway), ERK, JNK, c‐fos, p38 (MAPK pathway) and Akt (AKT pathway), and reduced the expression levels of Cathepsin K, CTR, MMP‐9 and TRAP. Guaiacol also suppressed the expression of nuclear factor of activated T‐cells cytoplasmic 1(NFATc1) and the RANKL‐induced Ca2+ oscillation. In vivo, it ameliorated ovariectomy‐induced bone loss by suppressing excessive osteoclastogenesis. Taken together, our findings suggest that guaiacol inhibits RANKL‐induced osteoclastogenesis by blocking the interactions of RANK with TRAF6 and C‐Src, and by suppressing the NF‐κB, MAPK and AKT signalling pathways. Therefore, this compound shows therapeutic potential for osteoclastogenesis‐related bone diseases, including postmenopausal osteoporosis.

Recognized for nearly 100 years, bone marrow adipocytes (BMAs) form bone marrow niches that contain hematopoietic and bone cells, the roles of which have long been underestimated. Distinct from canonical white, brown, and beige adipocytes, BMAs derived from bone marrow mesenchymal stromal cells possess unique characteristics and functions. Recent single-cell sequencing studies have revealed the differentiation pathway, and seminal works support the tenet that BMAs are critical regulators in hematopoiesis, osteogenesis, and osteoclastogenesis. In this review, we discuss the origin and differentiation of BMAs, as well as the roles of BMAs in hematopoiesis, osteogenesis, osteoclastogenesis, and immune regulation. Overall, BMAs represent a novel target for bone marrow-related diseases, including osteoporosis and leukemia.

Accumulating evidence has suggested the significant potential of chemically modified hydrogels in bone regeneration. Despite the progress of bioactive hydrogels with different materials, structures and loading cargoes, the desires from clinical applications have not been fully validated. Multiple biological behaviors are orchestrated precisely during the bone regeneration process, including bone marrow mesenchymal stem cells (BMSCs) recruitment, osteogenic differentiation, matrix calcification and well-organized remodeling. Since matrix metalloproteinases play critical roles in such bone metabolism processes as BMSC commitment, osteoblast survival, osteoclast activation matrix calcification and microstructure remodeling, matrix metalloproteinase (MMP) cleavable peptides-based hydrogels could respond to various MMP levels and, thus, accelerate bone regeneration. In this review, we focused on the MMP-cleavable peptides, polymers, functional modification and crosslinked reactions. Applications, perspectives and limitations of MMP-cleavable peptides-based hydrogels for bone regeneration were then discussed.

Postmenopausal osteoporosis is characterized by excess osteoclastogenesis which leads to net bone loss and brittle fractures. Studies have demonstrated that estrogen deficiency-associated bone loss is microbiota-dependent and could be prevented by probiotics and prebiotics. In this study, we report that orally administered lactulose (20 g/kg, 6 weeks) orally administered significantly inhibited osteoclastogenesis, bone resorption, and prevented ovariectomy (OVX)-induced bone loss in mice. Lactulose increased intestinal Claudin 2, 3 and 15, compared to the OVX group, and lowered pro-osteoclastogenic cytokines levels including tumor necrosis factor-α, interleukin(IL)-6, receptor activator of nuclear factor kappa-Β ligand (RANKL), and IL-17 as well as increased the anti-inflammatory cytokine IL-10 in the intestine, peripheral blood, and bone marrow. Lactulose significantly preserved the number of Foxp3+ Treg cells in the intestines compared with that in OVX mice. Lactulose altered the composition of intestinal microbiota measured by 16s rDNA sequencing and increased intestinal and serum short-chain fatty acids (SCFAs) levels including acetate, propionate and butyrate which were decreased in OVX mice as measured by gas chromatography. Oral administration of lactulose for 2 weeks significantly lowered the level of bone resorption marker C-telopeptide of type 1 collagen-1 in healthy male young volunteers (aging 20-25 years). In conclusion, lactulose inhibited osteoclastogenesis and bone resorption by altering the intestinal microbiota and increasing SCFAs. Lactulose could serve as an ideal therapeutic agent for postmenopausal osteoporosis.

Osteoarthritis comprises several joint disorders characterized by articular cartilage degeneration and persistent pain, causing disability and economic burden. The incidence of osteoarthritis is rapidly increasing worldwide due to aging and obesity trends. Basic and clinical research on osteoarthritis has been carried out for decades, but many questions remain unanswered. The exact role of subchondral bone during the initiation and progression osteoarthritis remains unclear. Accumulating evidence shows that subchondral bone lesions, including bone marrow edema and angiogenesis, develop earlier than cartilage degeneration. Clinical interventions targeting subchondral bone have shown therapeutic potential, while others targeting cartilage have yielded disappointing results. Abnormal subchondral bone remodeling, angiogenesis and sensory nerve innervation contribute directly or indirectly to cartilage destruction and pain. This review is about bone-cartilage crosstalk, the subchondral microenvironment and the critical role of both in osteoarthritis progression. It also provides an update on the pathogenesis of and interventions for osteoarthritis and future research targeting subchondral bone.

The development of a bioactive nanocomposite for bone replacement has gained much interest in the field of bone grafting. In this study, a nano fluorapatite (n-FA)–poly(butylene succinate) (PBS) bioactive composite was fabricated using a co-solution method. The results showed that the n-FA–PBS composite had improved hydrophilicity, compressive strength and an elastic modulus, which were obviously higher than those of PBS alone. In addition, the n-FA–PBS composite could inhibit bacterial attachment, with the number of viable bacteria on the composite obviously lower than on pure PBS, indicating good antibacterial ability. Moreover, the attachment and proliferation of human mesenchymal stem cells (hMSCs) on the n-FA–PBS composite was significantly higher than on PBS, and the alkaline phosphatase (ALP) activity of hMSCs on the composite was expressed at significantly higher levels compared to PBS. Furthermore, the hMSCs showed intimate contact with the composite surface and the cells spread and grew significantly better on the composite compared to PBS. Therefore, incorporation of n-FA into PBS is a good way to prepare an inorganic–organic bioactive composite of a nano ceramic and a polymer, which supports cell attachment, proliferation and differentiation. The implantation of the n-FA–PBS composite into the femoral bone of rabbits confirmed that the new bone tissue could form on the composite surfaces, and the composite combined directly with the natural bone tissue without fibrous capsule tissue, showing good osteoconductivity. In short, the n-FA–PBS bioactive composite has good biocompatibility and bioactivity, and has potential application in bone regeneration.

Adhesion GPCR Gpr126/Adgrg6 regulates mouse body length and bone mass by controlling osteoblast differentiation., Adhesion G protein–coupled receptor G6 (Adgrg6; also named GPR126) single-nucleotide polymorphisms are associated with human height in multiple populations. However, whether and how GPR126 regulates body height is unknown. In this study, we found that mouse body length was specifically decreased in Osx-Cre;Gpr126fl/fl mice. Deletion of Gpr126 in osteoblasts resulted in a remarkable delay in osteoblast differentiation and mineralization during embryonic bone formation. Postnatal bone formation, bone mass, and bone strength were also significantly affected in Gpr126 osteoblast deletion mice because of defects in osteoblast proliferation, differentiation, and ossification. Furthermore, type IV collagen functioned as an activating ligand of Gpr126 to regulate osteoblast differentiation and function by stimulating cAMP signaling. Moreover,the cAMP activator PTH(1–34), could partially restore the inhibition of osteoblast differentiation and the body length phenotype induced by Gpr126 deletion.Together, our results demonstrated that COLIV-Gpr126 regulated body length and bone mass through cAMP-CREB signaling pathway.

Background: Osteoporosis is a common metabolic bone disease, which always leads to osteoporotic fractures especially among the elderly. Biomarkers of bone mineral density (BMD) are helpful for prevention and early diagnosis of osteoporosis. This study aims to identify metabolomic biomarkers of low BMD. Methods: We included 701 participants who had BMD measures by dual-energy X-ray absorptiometry scans and donated fasting plasma samples from three clinical centers as a discovery set and another 278 participants from the fourth center as an independent replication set. We used a liquid chromatography-mass spectrometry-based metabolomics approach to profile the global circulating metabolites. Results: Among the 265 named metabolites identified in our study, six were associated with low BMD (FDR-adjusted P

Background Meta-Analyses are the basis of professional and healthcare agencies recommendations and have a growing importance. Quality of meta-analyses has been investigated in some medical fields but to our best knowledge this issue remains under investigated in orthopedics. Therefore, we performed a systematic analysis to: 1) after the introduction of PRISMA statement as a comprehensive guideline and the use of the AMSTAR tool as the standard for sufficient review methodology, has the quality of MAs improved because of that? 2) have some general characteristics influenced the quality of MAs (country, funding source, number of authors)? Material and Methods We systematically searched the meta-analyses in the top four journals with the impact factor (2015) as following: JBJS, Osteoarthritis Cartilage Arthroscopy and Clin Orthop Relat Res from 2005 to 2008 and from 2012 to 2015. Likewise from 2012–2015, we also analyzed the meta-analyses from OTSR. Characteristics were extracted based on the PRISMA statement and the AMSTAR tool. Country, number of authors, funding source were also extracted. Results A total of 154 meta-analyses were included in the present study. Score with PRISMA statement and the AMSTAR checklist were 20.86 ± 3.04 out of a maximum of 27 and 7.86 ± 1.55 out of a maximum of 11. The best journal was OTSR according to the PRISMA (23.06 ± 1.92) and AMSTAR (9.13 ± 0.87) scores. And the worst journal was Clin Orthop Relat Res according to the PRISMA score (19.4 ± 2.70) and JBJS according to the AMSTAR score (6.78 ± 1.65). Twelve items showed significant difference in the PRISMA statement, and five items in the AMSTAR checklist. Integral score of PRISMA statement and AMSTAR checklist has a significant difference between 2005-2008 and 2012–2015. The MAs reported from U.S. (56, 36.4%) were more than any other region in the world. And the MAs published by Asia/Oceania increased remarkably between these two period times [from (4, 10.8%) to (45, 38.5%)]. Conclusion This study showed that methodological reporting quality of meta-analyses in the major orthopedics journals has improved after the publication of the PRISMA statement. Level of evidence Level III.

According to the previously reported potent dual l-peptide PMI of p53-MDM2/MDMX interactions, a series of d-amino acid mutational PMI analogues, PMI-1-4, with enhanced proteolytic resistence and in vitro tumor cell inhibitory activities were reported, of which Liposome-PMI-1 showed a stronger inhibitory activity against the U87 cell lines than Nutlin-3. This d-amino acid mutation strategy may give a hand for enhancing the potential of peptide drugs.

Osteoporosis is a metabolic bone disease characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content. The imbalance between osteogenesis by osteoblasts and osteoclastogenesis by osteoclasts contributes to the pathogenesis of postmenopausal osteoporosis. Estrogen withdrawal leads to increased levels of proinflammatory cytokines. Overactivated osteoclasts by inflammation play a vital role in the imbalance. Matrine is an alkaloid found in plants from the Sophora genus with various pharmacological effects, including anti-inflammatory activity. Here we demonstrate that matrine significantly prevented ovariectomy-induced bone loss and inhibited osteoclastogenesis in vivo with decreased serum levels of TRAcp5b, TNF-α, and IL-6. In vitro matrine significantly inhibited osteoclast differentiation induced by receptor activator for NF-κB ligand (RANKL) and M-CSF in bone marrow monocytes and RAW264.7 cells as demonstrated by tartrate-resistant acid phosphatase (TRAP) staining and actin-ring formation as well as bone resorption through pit formation assays. For molecular mechanisms, matrine abrogated RANKL-induced activation of NF-κB, AKT, and MAPK pathways and suppressed osteoclastogenesis-related marker expression, including matrix metalloproteinase 9, NFATc1, TRAP, C-Src, and cathepsin K. Our study demonstrates that matrine inhibits osteoclastogenesis through modulation of multiple pathways and that matrine is a promising agent in the treatment of osteoclast-related diseases such as osteoporosis.—Chen, X., Zhi, X., Pan, P., Cui, J., Cao, L., Weng, W., Zhou, Q., Wang, L., Zhai, X. Zhao, Q., Hu, H., Huang, B., Su, J. Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis.

In this study, composite cements containing mesoporous magnesium silicate (m-MS) and calcium sulfate (CS) were fabricated. The results revealed that the setting time of the m-MS/CS composite cements (m-MSC) slightly prolonged with the increase of m-MS content while the compressive strength suffered a little loss. The doping of m-MS improved the water absorption, drug release (vancomycin) and degradability of the m-MSC in Tris-HCl solution (pH=7.4). In addition, addition of m-MS facilitated the apatite-mineralization of m-MSC in simulated body fluid (SBF), indicating good bioactivity. For cell cultural experiments, the results revealed that the m-MSC promoted the cells adhesion and proliferation, and improved the alkaline phosphatase (ALP) activity of MC3T3-E1 cells, revealing good cytocompatibility. It could be suggested that the m-MSC might be promising cements biomaterials for bone tissue regeneration.

Liehu Cao,1,* Weizong Weng,1,* Xiao Chen,1,* Jun Zhang,1 Qirong Zhou,1 Jin Cui,1 Yuechao Zhao,1 Jung-Woog Shin,2 Jiacan Su1 1Department of Orthopaedics Trauma, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 2Department of Biomedical Engineering, Inje University, Gimhae, Republic of Korea *These authors contributed equally to this work Abstract: Nanoporous lithium doping magnesium silicate (nl-MS) was introduced into calcium sulfate hemihydrate to prepare calcium sulfate composite (nl-MSC) bone cements. The introduction of nl-MS improved the in vitro degradability of nl-MSC cements, which could neutralize acidic degradable products of calcium sulfate and prevented the pH from dropping. The cements were implanted into the bone defects of femur bone of rabbits, and the results of histological and immunohistochemical analysis revealed that massive new bone tissue formed in the defects while the cements were degradable, indicating that the osteogenesis and degradability of the nl-MSC cements were much better than the control calcium sulfate dihydrate (CSD) cements. Furthermore, the positive expression of vascular endothelial growth factor and collagen type I for nl-MSC cements was higher than CSD, indicating that addition of nl-MS into the cements enhanced vascularization and osteogenic differentiation. The results suggested that the nl-MSC cements with good biocompatibility and degradability could promote vascularization and osteogenesis, and had great potential to treat bone defects. Keywords: bone cements, nanoporous lithium doping magnesium silicate, degradability, vascularization, osteogenesis

Infected bone defects (IBD) are a challenging problem in orthopedic practice. Biomaterials have attracted attention as a novel approach to overcome this challenge instead of using conventional strategies. Graphene, a two-dimensional carbon allotrope, has been shown to possess multiple advantages, such as osteogenesis-promoting activity, a large surface area for drug delivery, and antibacterial activities. However, these attractive merits have not been entirely explored or introduced for the management of IBD. Herein, a novel approach using a vancomycin-laden, self-assembled, graphene-based material against IBD was developed, and the approach uses a single-stage bone graft instead of multiple procedures. Owing to the π–π bonding with graphene, vancomycin can be promptly delivered in the initial stage, followed by a sustained release, which ensures the rapid elimination of an infection and provides a durable pathogen revival inhibition via the inherent antibacterial activity of graphene. Moreover, the 3D porous structure incorporated with nano-hydroxyapatite (nHA) provided a biomimetic microenvironment favored by cell adhesion and osteogenic differentiation. Further evaluation of this system in an IBD animal model demonstrated prompt control of infection and promotion of bone regeneration. These results revealed the potential of this approach to be an effectual solution for IBD treatment and a new area of graphene application in the future.

Exosomes, also known as extracellular vesicles, are naturally occurring, biocompatible, and bioacive nanoparticles ranging from 40 to 150 nm in diameter. Bone-secreted exosomes play important roles in bone homeostasis, the interruption of which can lead to diseases such as osteoporosis, rheumatoid arthritis, and osteopetrosis. Though the relationship between vascular and bone homeostasis has been recognized recently, the role of vascular endothelial cell (EC)-secreted exosomes (EC-Exos) in bone homeostasis is not well understood. Herein, we found that EC-Exos show more efficient bone targeting than osteoblast-derived exosomes or bone marrow mesenchymal stem cell-derived exosomes. We also found that EC-Exos can be internalized by bone marrow-derived macrophages (BMMs) to alter their morphology. EC-Exos can inhibit osteoclast activity in vitro and inhibit osteoporosis in an ovariectomized mouse model. Sequencing of exosome miRNA revealed that miR-155 was highly expressed in EC-Exos-treated BMMs. The miR-155 level in EC-Exos was much higher than that in BMMs and ECs, indicating that miR-155 was endogenous cargo of EC-derived vesicles. Blockage of BMMs miR-155 levels reversed the suppression by EC-Exos of osteoclast induction, confirming that exosomal miR-155 may have therapeutic potential against osteoporosis. Taken together, our findings suggest that EC-Exos may be utilized as a bone targeting and nontoxic nanomedicine for the treatment of bone resorption disorders.

Background: Osteoporosis is a common metabolic bone disease, which always leads to osteoporotic fractures. Biomarkers of bone mineral density (BMD) are helpful for prevention and early diagnosis of osteoporosis. This study aims to identify metabolomic biomarkers of low BMD. Methods: We included 701 participants who had BMD measures by dual-energy X-ray absorptiometry scans and donated fasting plasma samples from three clinical centres as a discovery set and another 278 participants from the fourth centre as an independent replication set. We used a liquid chromatography-mass spectrometry-based metabolomics approach to profile the global metabolites of fasting plasma. Findings: Among the 265 named metabolites identified in our study, six were associated with low BMD (FDR-adjusted P

Background In recent years, the number of randomized controlled trials (RCTs) in the field of orthopaedics is increasing in Mainland China. However, randomized controlled trials (RCTs) are inclined to bias if they lack methodological quality. Therefore, we performed a survey of RCT to assess: (1) What about the quality of RCTs in the field of orthopedics in Mainland China? (2) Whether there is difference between the core journals of the Chinese department of orthopedics and Orthopaedics Traumatology Surgery & Research (OTSR). Material and methods This research aimed to evaluate the methodological reporting quality according to the CONSORT statement of randomized controlled trials (RCTs) in seven key orthopaedic journals published in Mainland China over 5 years from 2010 to 2014. All of the articles were hand researched on Chongqing VIP database between 2010 and 2014. Studies were considered eligible if the words “random”, “randomly”, “randomization”, “randomized” were employed to describe the allocation way. Trials including animals, cadavers, trials published as abstracts and case report, trials dealing with subgroups analysis, or trials without the outcomes were excluded. In addition, eight articles selected from Orthopaedics Traumatology Surgery & Research (OTSR) between 2010 and 2014 were included in this study for comparison. The identified RCTs are analyzed using a modified version of the Consolidated Standards of Reporting Trials (CONSORT), including the sample size calculation, allocation sequence generation, allocation concealment, blinding and handling of dropouts. Results A total of 222 RCTs were identified in seven core orthopaedic journals. No trials reported adequate sample size calculation, 74 (33.4%) reported adequate allocation generation, 8 (3.7%) trials reported adequate allocation concealment, 18 (8.1%) trials reported adequate blinding and 16 (7.2%) trials reported handling of dropouts. In OTSR, 1 (12.5%) trial reported adequate sample size calculation, 4 (50.0%) reported adequate allocation generation, 1 (12.5%) trials reported adequate allocation concealment, 2 (25.0%) trials reported adequate blinding and 5 (62.5%) trials reported handling of dropouts. There were statistical differences as for sample size calculation and handling of dropouts between papers from Mainland China and OTSR ( P Conclusion The findings of this study show that the methodological reporting quality of RCTs in seven core orthopaedic journals from the Mainland China is far from satisfaction and it needs to further improve to keep up with the standards of the CONSORT statement. Level of evidence Level III case control.

Hydrogen is a kind of noble gas with the character to selectively neutralize reactive oxygen species. Former researches proved that low-concentration of hydrogen can be used to ameliorating cerebral ischemia/reperfusion injury. Hydrogen electrolyzed from water has a hydrogen concentration of 66.7%, which is much higher than that used in previous studies. And water electrolysis is a potential new hydrogen resource for regular clinical use. This study was designed and carried out for the determination of safety and neuroprotective effects of water electrolysis-derived hydrogen. Sprague-Dawley rats were used as experimental animals, and middle cerebral artery occlusion was used to make cerebral ischemia/reperfusion model. Pathologically, tissues from rats in hydrogen inhalation group showed no significant difference compared with the control group in HE staining pictures. The blood biochemical findings matched the HE staining result. TTC, Nissl, and TUNEL staining showed the significant improvement of infarction volume, neuron morphology, and neuron apoptosis in rat with hydrogen treatment. Biochemically, hydrogen inhalation decreased brain caspase-3, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine-positive cells and inflammation factors concentration. Water electrolysis-derived hydrogen inhalation had neuroprotective effects on cerebral ischemia/reperfusion injury in rats with the effect of suppressing oxidative stress and inflammation, and it is a possible new hydrogen resource to electrolyze water at the bedside clinically.

Jun Hou,1 Donghui Fan,2 Lingming Zhao,2 Baoqin Yu,3 Jiacan Su,3 Jie Wei,2 Jung-Woog Shin4 1The First Affiliated Hospital of Anhui Medical University, Department of Oral and Maxillofacial Surgery, Hefei, 2Key Laboratory for Ultrafine Materials of Ministry of Education and The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 3Department of Orthopaedics Trauma, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 4Department of Biomedical Engineering, Inje University, Gimhae, Republic of Korea Abstract: Biocomposite scaffolds were fabricated by incorporation of nanobredigite (n-BD) into the polymer of poly(ε-caprolactone)–poly(ethyleneglycol)–poly(ε-caprolactone) (PCL–PEG–PCL). The results revealed that the addition of n-BD into PCL–PEG–PCL significantly improved water absorption, compressive strength, and degradability of the scaffolds of n-BD/PCL–PEG–PCL composite (n-BPC) compared with PCL–PEG–PCL scaffolds alone. In addition, the proliferation and alkaline phosphatase activity of MG63 cells cultured on n-BPC scaffolds were obviously higher than that cultured on PCL–PEG–PCL scaffolds. Moreover, the results of the histological evaluation from the animal model revealed that the n-BPC scaffolds significantly improved new bone formation compared with the PCL–PEG–PCL scaffolds, indicating good osteogenesis. The n-BPC scaffolds with good biocompatibility could stimulate cell proliferation, differentiation, and bone tissue regeneration and would be an excellent candidate for bone defect repair. Keywords: nanobredigite, PCL–PEG–PCL, biocomposite scaffolds, degradability, osteo­genesis

RANKL signaling is essential for osteoclastogenesis. Its role in osteoblastic differentiation and bone formation is unknown. Here we demonstrate that RANK is expressed at an early stage of bone marrow mesenchymal stem cells (BMSCs) during osteogenic differentiation in both mice and human and decreased rapidly. RANKL signaling inhibits osteogenesis by promoting β-catenin degradation and inhibiting its synthesis. In contrast, RANKL signaling has no significant effects on adipogenesis of BMSCs. Interestingly, conditional knockout of rank in BMSCs with Prx1-Cre mice leads to a higher bone mass and increased trabecular bone formation independent of osteoclasts. In addition, rankflox/flox: Prx1-Cre mice show resistance to ovariectomy-(OVX) induced bone loss. Thus, our results reveal that RANKL signaling regulates both osteoclasts and osteoblasts by inhibition of osteogenic differentiation of BMSCs and promotion of osteoclastogenesis., Developmental Genetics: A dual-use gene regulates bone formation and breakdown Researchers in China have shown that a gene known for breaking bones down is also involved in making new bone. Bones are constantly repaired and reshaped by cells which break down bone tissue, osteoclasts, and those which create new bone, osteoblasts. The RANKL gene is known to play an important role in osteoclast development, but Jiacan Su of the Second Military Medical University has shown that it is also important for osteoblasts. Su’s team detected high expression of RANKL and its receptor, RANK, in bone marrow stem cells, and the levels decreased as the stem cells differentiated into osteoblasts. Artificially increasing RANK expression decreased osteoblast differentiation, while reducing its expression increased osteoblast differentiation and bone mass. By showing that RANKL regulates osteoblasts as well as osteoclasts, these findings open new avenues for understanding bones development.

Osteoporosis, characterized by bone mass reduction and increased fractures, has become a global health problem that seriously affects the health of people, especially postmenopausal women; however, the current pathogenesis of postmenopausal osteoporosis (PMOP) has not been thoroughly elucidated to date. In this study, bilateral ovariectomy was performed to establish an OVX mouse model of osteoporosis. UPLC-Q-TOF-MS-based lipidomics in combination with metabolomics were used to analyze the femur tissue of osteoporosis mice. We found that 11 polar metabolites and 93 lipid metabolites were significantly changed and were involved in amino acid metabolism, nucleotide metabolism and lipid metabolism. Among the lipids, fatty acyls, glycerolipids, glycerophospholipids, sphingolipids and sterols showed robust changes. These results revealed that several metabolic disorders caused by changes in the hormone levels in OVX, especially disordered lipid metabolism, are closely related to the imbalance between bone resorption and formation and may underlie the development of PMOP. The data generated via lipidomics and metabolomics presented in this study shows good applicability and wide coverage in the construction of the metabolic profile of bone tissue. Therefore, this approach may provide the pathway focusing and data support at the metabolite level for the in-depth mechanism of PMOP.

A novel peptide stapling strategy based on the dithiocarbamate chemistry linking the side chains of residues Lys(i) and Cys(i + 4) of unprotected peptides is developed., Two major pharmacological hurdles severely limit the widespread use of small peptides as therapeutics: poor proteolytic stability and membrane permeability. Importantly, low aqueous solubility also impedes the development of peptides for clinical use. Various elaborate side chain stapling chemistries have been developed for α-helical peptides to circumvent this problem, with considerable success in spite of inevitable limitations. Here we report a novel peptide stapling strategy based on the dithiocarbamate chemistry linking the side chains of residues Lys(i) and Cys(i + 4) of unprotected peptides and apply it to a series of dodecameric peptide antagonists of the p53-inhibitory oncogenic proteins MDM2 and MDMX. Crystallographic studies of peptide–MDM2/MDMX complexes structurally validated the chemoselectivity of the dithiocarbamate staple bridging Lys and Cys at (i, i + 4) positions. One dithiocarbamate-stapled PMI derivative, DTCPMI, showed a 50-fold stronger binding to MDM2 and MDMX than its linear counterpart. Importantly, in contrast to PMI and its linear derivatives, the DTCPMI peptide actively traversed the cell membrane and killed HCT116 tumor cells in vitro by activating the tumor suppressor protein p53. Compared with other known stapling techniques, our solution-based DTC stapling chemistry is simple, cost-effective, regio-specific and environmentally friendly, promising an important new tool for the development of peptide therapeutics with improved pharmacological properties including aqueous solubility, proteolytic stability and membrane permeability.

Bone metabolism is determined by a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts. The imbalance due to over-activated osteoclasts plays an important role in various diseases. Activation of NF-κB and MAPK signaling pathways by receptor activator of nuclear factor -κB ligand (RANKL) is vital for osteoclastogenesis. Here, we for the first time explored the effects of 18β-glycyrrhetinic acid (18β-GA), a pentacyclic triterpenoid found in the Glycyrrhiza glabra L roots, on RANKL-induced osteoclastogenesis, osteoclast functions and signaling pathways in vitro and in vivo. In bone marrow monocytes (BMMs) and RAW264.7 cells, 18β-GA inhibited osteoclastogenesis, decreased expression of TRAP, cathepsin K, CTR and MMP-9, blocked actin ring formation and compromised osteoclasts functions in a dose-dependent manner at an early stage with minimal effects on osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). For underlying molecular mechanisms, 18β-GA inhibited RANKL-induced phosphorylation of p65, p50, and IκB, blocked p65 nuclear translocation and decreased the DNA-binding activity of NF-κB. Besides, 18β-GA inhibited the activation of the MAPK pathways. Co-immunoprecipitation showed that 18β-GA treatment blocked RANK–TRAF6 association at an upstream site. In vivo, 18β-GA treatment inhibited ovariectomy-induced osteoclastogenesis and reduced bone loss in mice. Overall, our results demonstrated that 18β-GA inhibited RANKL-induced osteoclastogenesis by inhibiting RANK expression in preosteoclasts and blocking the binding of RANK and TRAF6 which lead to the inhibition of NF-κB and MAPK signaling pathways. 18β-GA is a promising novel candidate in the treatment of osteoclast-related diseases such as postmenopausal osteoporosis.

Macro-mesoporous scaffolds based on wheat gliadin (WG)/mesoporous magnesium calcium silicate (m-MCS) biocomposites (WMC) were developed for bone tissue regeneration. The increasing amount of m-MCS significantly improved the mesoporosity and water absorption of WMC scaffolds while slightly decreased their compressive strength. With the increase of m-MCS content, the degradability of WMC scaffolds was obviously enhanced, and the decrease of pH value could be slow down after soaking in Tris-HCl solution for different time. Moreover, the apatite mineralization ability of the WMC scaffolds in simulated body fluid (SBF) was obviously improved with the increase of m-MCS content, indicating good bioactivity. The macro-mesoporous WMC scaffolds containing m-MCS significantly stimulated attachment, proliferation and differentiation of MC3T3-E1 cells, indicating cytocompatibility. The WMC scaffold containing 40 w% m-MCS (WMC40) possessed the highest porosity (including macroporosity and mesoporosity), which loaded the highest amount of curcumin (CU) as well as displayed the slow release of CU. The results suggested that the incorporation of m-MCS into WG produced biocomposite scaffolds with macro-mesoporosity, which significantly improved water absorption, degradability, bioactivity, cells responses and load/sustained release of curcumin.

Background/Aims: Bone homeostasis is associated with the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Unbalanced bone homeostasis as a result of reduced osteogenesis or excessive osteoclastogenesis can lead to disorders such as osteoporosis, Paget’s disease, and rheumatoid arthritis. Shikimic acid is a cyclohexanecarboxylic acid, reported to exhibit pharmacological properties including anti-inflammatory and antioxidant activities. However, its effects on bone homeostasis remain unknown. Methods: First, the in vitro MTT cell viability assay was performed. Tartrate-resistant acid phosphatase (TRAP) and actin ring formation assays, as well as immunofluorescence staining were then performed to evaluate osteoclastogenesis. Potential signaling pathways were characterized by western blotting and verified in overexpression experiments. Related factors were examined by western blotting, reverse transcription polymerase chain reaction, electrophoretic mobility shift assay, and co-immunoprecipitation. Ovariectomized mice were used for the in vivo study. Results: TRAP staining showed that shikimic acid significantly inhibited osteoclastogenesis and pit resorption in bone marrow monocytes and RAW264.7 cells, and actin ring formation assays showed that shikimic acid suppressed the bone resorption function of osteoclasts. Furthermore, shikimic acid inhibited the receptor activator of nuclear factor-κB RANK/tumor necrosis factor receptor-associated factor 6 (TRAF6) association, suppressed nuclear factor-κB and mitogen-activated protein kinase signaling pathways, and downregulated nuclear factor of activated T-cell cytoplasmic 1. The expression of osteoclastogenesis biomarkers, including TRAF6, calcitonin receptor, TRAP, cathepsin K, and matrix metalloproteinase-9, was inhibited. In vivo, shikimic acid also significantly ameliorated bone loss and prevented osteoclastogenesis in ovariectomized mice. Conclusion: Shikimic acid inhibited osteoclastogenesis and osteoclast function by blocking RANK ligand-induced recruitment of TRAF6, as well as downstream signaling pathways in vitro. Shikimic acid also reduced ovariectomy-induced osteoclastogenesis and bone loss in vivo.

To study the effects of Wharton's jelly cells (WJCs) on acute spinal cord injury (SCI), 81 rats were divided into a sham surgery group, a model group, and a WJC transplantation group (n = 27). Motor functions of the model and WJC transplantation groups were partially recovered, and the recovery was better in the latter group. The WJC transplantation group had integral spinal cord tissues. Compared with the model group, the WJC transplantation group expressed significantly less interleukin-1β (IL-1β) and more nerve growth factor (NGF) (P < 0.05). WJC transplantation changed the microenvironment of the SCI site, inhibited IL-1β expression, increased NGF expression, promoted the recovery of neurological function, and relieved secondary SCI.

Bioactive scaffolds of the mesoporous bioglass (m-BG) and poly(l-lactide) (PLLA) composite were fabricated using a solvent casting-particulate leaching method. The results showed that incorporation of the m-BG into PLLA significantly improved the in vitro water absorption, degradability and apatite-formation ability of the m-BG-PLLA composite scaffolds, which were m-BG content dependent. Moreover, addition of the m-BG into PLLA could neutralize the acidic degradation products of PLLA and thus compensate for the decrease of the pH value. In cell culture experiments, the results revealed that the m-BG-PLLA composite scaffolds enhanced attachment, proliferation and alkaline phosphatase (ALP) activity of MC3T3-E1 cells, which were m-BG content dependent. In animal experiments, the SRmCT and histological elevation results showed that the composite scaffolds significantly improved osteogenesis in vivo. It can be suggested that incorporation of bioactive materials of m-BG into PLLA was a useful approach to obtain composite scaffolds with improved properties (such as water absorption, degradability, bioactivity and osteogenesis), and the composite scaffolds with excellent biocompatibility could be promising bioactive implants for bone regeneration.

Recently, honeycomb-patterned polymeric films have been fabricated through breath-figure method to mimic the topographical feature of the basement membrane and this topography was demonstrated to enhance osteoblast functions including adhesion, spreading, proliferation, and differentiation. However, honeycomb-patterned films incorporated with other components benefiting osteoblast functions have not been reported yet. In this study, we report the fabrication of nano-hydroxyapatite (nHA) (3 wt%, 5 wt%, and 7 wt%) incorporated honeycomb poly(L-lactide) (PLLA) films to evaluate the effect of nHA on the self-assembly of honeycomb pores in PLLA films. Scanning electron microscopy (SEM) images demonstrated that 5 wt% nHA in PLLA resulted in the most regular honeycomb pores. Water contact angle test and protein adsorptions including fibronectin (FN) and serum were performed on 5 wt% nHA incorporated honeycomb PLLA films (H-PLLA/nHA), as well as the controls, flat PLLA films (F-PLLA), honeycomb PLLA films (H-PLLA), and flat HA films (F-HA). Honeycomb pores in H-PLLA films enhanced hydrophobicity compared with F-PLLA films, whereas nHA particles in H-PLLA/nHA films lowered the hydrophobicity compared with H-PLLA. Both the FN and serum protein adsorptions were increased on H-PLLA films compared with F-PLLA, but decreased significantly on H-PLLA/nHA films compared with H-PLLA films. Further, MC3T3-E1 mouse newborn calvaria preosteoblasts were employed to investigate the cell functions in terms of cell adhesion, spreading, proliferation, and differentiation on those films. The results strongly indicated that those cell functions were promoted on honeycomb films, especially H-PLLA/nHA films, compared with F-PLLA films and they did not show a significant difference between H-PLLA films and F-HA films.

The damage-associated molecular pattern molecules (DAMPs) released by necrotic cells can trigger inflammatory response, which will facilitate the clearance of these dead cells. Neutrophil mobilization is a very important step for the dead cell clearance, however the detailed mechanisms for DAMPs induce neutrophil mobilization remains largely elusive. In this study, by using a necrotic cell-induced neutrophil mobilization mice model, we found that both neutrophil number and percentage rapidly (as early as 30 min) increased with necrotic cells but not live cell treatment. CXCL1 was rapidly increased in the serum and was responsible for the neutrophil mobilization when treated with necrotic cells. We further demonstrated that the hepatocytes in the liver were the main source of CXCL1 production in response to necrotic cells challenge. However, the hepatocytes did not express CXCL1 when incubating with necrotic cells alone. When Kupffer cells were ablated, the increased CXCL1 levels as well as neutrophil mobilization were abolished with necrotic cells challenge. Moreover, we clarified Kupffer cells-derived TNF-α activates the NF-κB pathway in hepatocytes and promote hepatocytes to express CXCL1. In summary, we showed that the liver is the main source for necrotic cell-induced CXCL1 production and neutrophil mobilization. Kupffer cells in the liver sense DAMPs and release TNF-α to activate the NF-κB pathway in hepatocytes. The interaction between Kupffer cells and hepatocytes is critical for CXCL1 production.

Osteoporosis is a metabolic bone disease characterized by low bone mass and micro-architectural deterioration of bone, for which the underlying mechanism is an imbalance between bone resorption and bone remodeling. The protein-protein interactions between receptor activator of nuclear factor-κB ligand (RANKL), RANK (its receptor), and osteoprotegerin (OPG), are known to mediate the development and activation of osteoclasts in bone remodeling, and are regarded as a pivotal therapeutic target for the treatment of osteoporosis. Herein, we disclose the successful development of a novel glycopeptide (OM-2), the structure of which is based on the key interacting sites of the reported RANKL and OPG crystal structure. OM-2 exhibited potent binding affinity with RANKL and resistance to degradation by protease enzymes. It also blocked RANKL/RANK interactions, and inhibited osteoclastogenesis in vitro. In vivo studies confirmed that OM-2 could effectively reduce bone loss and inhibit osteoclast activation in ovariectomized (OVX) mice at a dosage of 20.0 mg/kg/day. Accordingly, OM-2 is suggested as a therapeutic candidate for postmenopausal osteoporosis (PMOP) and osteoclastogenesis-related diseases like rheumatoid arthritis (RA). More importantly, its identification validates our structure-based strategy for the development of drugs that target the RANKL/RANK/OPG system.

Background/Aims: Hydrogen selectively neutralizes reactive oxygen species (ROS) and ameliorates various ROS-induced injuries. Spinal cord injury (SCI) is a serious injury to the central nervous system, and secondary SCI is closely related to excessive ROS generation. We hypothesized that hydrogen inhalation ameliorates SCI, and the mechanism of action may be related to the protective effects of hydrogen against oxidative stress, apoptosis, and mitochondrial damage. Methods: Mechanically injured spinal cord neurons were incubated with different concentrations of hydrogen in vitro. Immunofluorescence staining and transmission electron microscopy were used to confirm the protective effects of hydrogen. ROS and related proteins were detected with dihydroethidium fluorescence staining, enzyme-linked immunosorbent assays, and western blotting. Terminal deoxynucleotidyl transferase dUTP nick end labeling assays, flow cytometry, and western blotting were used to detect neuronal apoptosis. ATP concentrations, Janus Green B staining, and mitochondrial permeability transition pore (mPTP) status were assessed to investigate mitochondrial damage. RNA sequencing was performed to screen potential target genes of hydrogen application. Hydrogen was administered to mice after spinal cord contusion injury was established for 42 days. The Basso Mouse Scale (BMS) and footprint analyses were used to assess locomotor functions, and immunofluorescence staining of the injured spinal cord segments was performed to detect oxidative stress status. Results: Spinal cord neurons were preserved by hydrogen administration after mechanical injury in a dose-dependent manner. ROS generation, oxidative stress injury-related markers, and the number of apoptotic neurons were significantly reduced after hydrogen treatment. The ATP production and mPTP function in injured neurons were preserved by hydrogen incubation. The expression levels of Cox8b, Cox6a2, Cox7a1, Hspb7, and Atp2a1 were inhibited by hydrogen treatment. BMS scores and the footprint assessment of mice with SCI were improved by hydrogen inhalation. Conclusions: Hydrogen inhalation (75%) ameliorated SCI in vivo and attenuated neuronal mechanical injuries in vitro, and its protective effect on spinal cord neurons was exerted in a dose-dependent manner. The underlying mechanisms included reducing ROS generation and oxidative stress, inhibiting neuronal apoptosis, and restoring mitochondrial construction and function. Cox8b, Cox6a2, Cox7a1, Hspb7, and Atp2a1 were identified as potential target genes of hydrogen treatment.

Background The Achilles tendon Total Rupture Score (ATRS), which is originally developed in 2007 in Swedish, is the only patient-reported outcome measure (PROM) for specific outcome assessment of an Achilles tendon rupture.Purpose of this study is to translate and cross-culturally adapt Achilles tendon Total Rupture Score (ATRS) into simplified Chinese, and primarily evaluate the responsiveness, reliability and validity. Methods International recognized guideline which was designed by Beaton was followed to make the translation of ATRS from English into simplified Chinese version (CH-ATRS). A prospective cohort study was carried out for the cross-cultural adaptation. There were 112 participants included into the study. Psychometric properties including floor and ceiling effects, Cronbach’s alpha, intraclass correlation coefficient, effect size, standard response mean, and construct validity were tested. Results The mean scores of CH-ATRS are 57.42 ± 13.70. No sign of floor or ceiling effect was found of CH-ATRS. High level of internal consistency was supported by the value of Cronbach’s alpha (0.893). ICC (0.979, 95%CI: 0.984-0.993) was high to indicate the high test-retest reliability. Great responsive ness was proved with the high absolute value of ES and SRM (0.84 and 8.98, respectively). The total CH-ATRS score had very good correlation with physical function and body pain subscales of SF-36 (r = −0.758 and r = −0.694, respectively, p

To elucidate the methodological reporting quality of randomized controlled trials (RCTs) in three spine journals from 2010 to 2012. In this study, we summarized the methodological report of RCTs in three major spine journals, including the Spine Journal, Spine and the European Spine Journal from 2010 to 2012. The methodological reporting quality, including the allocation sequence generation, allocation concealment, blinding and sample size calculation, was revealed. Number of patients, funding source, type of intervention and country were also retrieved from each trial. The methodological reporting quality was descriptively reported. Ninety trials were involved and 57.8 % (52/90) reported adequate allocation sequence generation, 46.7 % (42/90) reported adequate allocation concealment, 34.4 % (31/90) reported adequate blinding and 37.8 % (34/90) reported adequate sample size calculation. This study shows that the methodological reporting quality of RCTs in the spine field needs further improvement.

The objective of this study was to compare replacement of the radial head by metal prostheses with open reduction and internal fixation (ORIF) for the treatment of unstable, multi-fragmented radial head fractures. A prospective randomised controlled trial was employed to investigate 45 patients with unstable, multi-fragmented fractures of the radial head, from January 2004 to June 2007. The patients were randomised to two groups: the ORIF group and the radial head replacement group. Over the next two years, follow-up assessments recorded Broberg and Morrey scores and postoperative complication rate. Statistical analysis was performed. According to Broberg and Morrey scores, patients receiving radial head replacement achieved significantly better clinical results with 91% (20/22) good or excellent compared to patients assigned to the ORIF group with 65.2% (15/23) good or excellent results (P

Transplantation of olfactory ensheathing cells (OECs) has emerged as a very promising therapy for spinal cord injury (SCI). Also, local delivery of NT-3 can counteract pathological events and induce a regenerative response after SCI. Supplement of exogenetic NT-3 might be a new approach to SCI repair. In this study, we examined the therapeutic effect of rat NT-3 gene-modified OECs transplantation on SCI. Rat NT-3 gene was transfected into OECs using a retroviral system. The engineered NT-3-OECs were tested for their ability to express and secrete biologically active NT-3 in vitro. Then NT-3-OECs were implanted into contused T9 spinal cord of the adult rats. Their ability of survival and NT-3 production was examined. The effect of axon regeneration was evaluated at the morphological level and promotion of locomotor functional recovery were assessed. The result showed that genetically modified OECs were capable of surviving and producing NT-3 in vivo to significantly improve the recovery after SCI.

Background Meta-analyses are the basis of professional and healthcare agencies recommendations and have a growing importance. Quality of meta-analyses has been investigated in some medical fields but to our best knowledge this issue remains fairly investigated in orthopedics. Therefore, we performed a systematic analysis to assess: (1) the quality of meta-analyses before and after the introduction of PRISMA statement as a comprehensive guideline and the use of the AMSTAR tool? (2) Have some general characteristics influenced the quality of meta-analyses (country, funding source)? Material and Methods We systematically searched the meta-analyses in the top four journals with the impact factor (2015) as following: Journal of Bone and Joint Surgery (JBJS), Osteoarthritis Cartilage, Arthroscopy, and Clinical Orthopaedics Related Research (CORR) from 2005 to 2008 and from 2012 to 2015. Likewise, from 2012–2015, we also analyzed the meta-analyses from Orthopaedics & Traumatology: Surgery & Research (OTSR). Characteristics were extracted based on the PRISMA statement and the AMSTAR tool. Country, number of authors, funding source were also extracted. Results A total of 154 meta-analyses were included in the present study. Score with PRISMA statement and the AMSTAR checklist were 20.86 ± 3.04 out of a maximum of 27 and 7.86 ± 1.55 out of a maximum of 11. The PRISMA score was 21.50 ± 2.69 in 2012–2015 (77% of items adequately reported, on average), has significant improvements compared with the PRISMA score in 2005–2008 (18.27 ± 3.03, P Conclusion This study showed that methodological reporting quality of meta-analyses in the major orthopedics journals has improved after the publication of the PRISMA statement. Level of evidence Level III case control study based on survey article.

From August 1990 to December 2007, 156 patients with humeral shaft nonunion were treated with our patented Ni-Ti shape memory alloy swan-like memory pressure connector (SMC). The SMC device cooled with ice before implantation was warmed to 40-50 degrees C after implantation to produce balanced axial and compression forces to stabilise the fracture three-dimensionally. This combined with autologous bone grafting achieved bone tissue regeneration in the fracture and promoted smooth recovery of joint function, with a nonunion healing rate of 98.7% after a single SMC implantation. Failure of nonunion healing occurred in only two cases but was successfully managed by a further operation. Complications were not found in any of these patients apart from four with pre-existing radial nerve injuries. These results demonstrate the effectiveness of the SMC device for the management of humeral shaft nonunion. The device provides continuous compression of the fracture with minimal trauma to the local blood supply.

Postmenopausal osteoporosis (POMP) is a public health problem characterized by decreased bone density and increased fracture risk. Over-activated osteoclastogenesis plays a vital role in POMP. Here we developed a novel bioactive compound MASM (M19) based on sophocarpine. Although it showed no significant effects on osteogenesis and adipogenesis for bone marrow-derived mesenchymal stem cells (BMSCs) in vitro, it could significantly inhibit RANKL/M-CSF induced osteoclastogenesis through suppressing NF-κB, MAPKs and PI3K/Akt pathways in vitro and ameliorate bone loss in ovariectomized mice in vivo. Ribosomal protein s5 (RPS5) has been identified as a target of M19 and regulates PI3K/Akt, NF-κB and MAPKs pathways in osteoclastogenesis. Overexpressions of RPS5 synergistically inhibited osteoclastogenesis with M19 while silencing RPS5 compromised M19 inhibitory effects on osteoclastogenesis in vitro. Among the three pathways, Akt plays a major role in M19 effects. The Akt activator SC79 partially reversed the inhibitory effects on osteoclastogenesis by M19 and RPS5-knocking-down. It indicates that RPS5 serves as a potential candidate target for inhibiting osteoclastogenesis and osteoporosis therapy and M19 is a promising agent for POMP treatment.

The aim of the present study was to investigate the outcomes of surgical treatment of calcaneal fractures of Sanders type II and III using a minimally invasive technique and a locking plate. We reviewed 33 feet in 33 consecutive patients with Sanders type II and III calcaneal fractures who had undergone a minimally invasive technique using percutaneous reduction and locking plates. All operations were performed by the same surgeons. The postoperative evaluation included radiographs, determination of restoration of Bohler’s angle and Gissane's angle, and administration of the American Orthopaedic Foot and Ankle Society ankle-hind foot scale, Maryland Foot Score, and visual analog scale of pain. The mean visual analog scale score was 1.6 ± 1.4 when radiographic fracture healing was observed. The median functional score of the 33 patients (33 feet) reached 82 (interquartile range 80 to 99) at the last follow-up evaluation according to the American Orthopaedic Foot and Ankle Society ankle-hind foot scale and 89 (interquartile range 80 to 99) according to Maryland Foot Score. All cases achieved restoration of a normal Bohler’s angle and Gissane's angle. Postoperative superficial infections occurred in 2 patients, subtalar arthritis developed in 2, and no soft tissue necrosis was observed. For Sanders type II and III fractures of the calcaneus bone, treatment with a minimally invasive technique combining percutaneous reduction and locking plate fixation provided satisfactory clinical results, with a lower incidence of complications. However, longer term studies with a larger sample size and more randomized controlled trials are required to define the superiority of our minimally invasive technique compared with conventional surgical treatment of calcaneal fractures.

Bioartificial bone tissue engineering is an increasingly popular technique to repair bone defect caused by injury or disease. This study aimed to investigate the feasibility of PLLA/PCL (poly-L-lactic acid/polycaprolactone) by a comparison study of PLLA/PCL and PLLA scaffolds applied in bone regeneration. Thirty healthy mature New Zealand rabbits on which 15 mm distal ulna defect model had been established were selected and then were divided into three groups randomly: group A (repaired with PLLA scaffold), group B (repaired with PLLA/PCL scaffold), and group C (no scaffold) to evaluate the bone-remodeling ability of the implants. Micro-CT examination revealed the prime bone regeneration ability of group B in three groups. Bone mineral density of surgical site in group B was higher than group A but lower than group C. Meanwhile, the bone regeneration in both groups A and B proceeded with signs of inflammation for the initial fast degradation of scaffolds. As a whole, PLLA/PCL scaffoldsin vivoinitially degrade fast and were better suited to repair bone defect than PLLA in New Zealand rabbits. Furthermore, for the low mineral density of new bone and rapid degradation of the scaffolds, more researches were necessary to optimize the composite for bone regeneration.

Background In recent years, the number of randomized controlled trials (RCTs) in the field of orthopaedics is increasing in Mainland China. However, randomized controlled trials (RCTs) are inclined to bias if they lack methodological quality. Therefore, we performed a survey of RCT to assess: (1) what about the quality of RCTs in the field of orthopedics in Mainland China? (2) Whether there is difference between the core journals of the Chinese Department of orthopedics and Orthopedics Traumatology Surgery & Research (OTSR). Material and methods This research aimed to evaluate the methodological reporting quality according to the CONSORT statement of randomized controlled trials (RCTs) in seven key orthopaedic journals published in Mainland China over 5 years from 2010 to 2014. All of the articles were hand researched on Chongqing VIP database between 2010 and 2014. Studies were considered eligible if the words “random”, “randomly”, “randomization”, “randomized” were employed to describe the allocation way. Trials including animals, cadavers, trials published as abstracts and case report, trials dealing with subgroups analysis, or trials without the outcomes were excluded. In addition, eight articles selected from Orthopedics Traumatology Surgery & Research (OTSR) between 2010 and 2014 were included in this study for comparison. The identified RCTs are analyzed using a modified version of the Consolidated Standards of Reporting Trials (CONSORT), including the sample size calculation, allocation sequence generation, allocation concealment, blinding and handling of dropouts. Results A total of 222 RCTs were identified in seven core orthopaedic journals. No trials reported adequate sample size calculation, 74 (33.4 %) reported adequate allocation generation, 8 (3.7 %) trials reported adequate allocation concealment, 18 (8.1 %) trials reported adequate blinding and 16 (7.2 %) trials reported handling of dropouts. In OTSR, 1 (12.5 %) trial reported adequate sample size calculation, 4 (50.0 %) reported adequate allocation generation, 1 (12.5 %) trials reported adequate allocation concealment, 2 (25.0 %) trials reported adequate blinding and 5 (62.5 %) trials reported handling of dropouts. There were statistical differences as for sample size calculation and handling of dropouts between papers from Mainland China and OTSR ( P Conclusion The findings of this study show that the methodological reporting quality of RCTs in seven core orthopaedic journals from the Mainland China is far from satisfaction and it needs to further improve to keep up with the standards of the CONSORT statement. Level of evidence Level III case control.