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Our research developed a novel approach to quantitatively evaluate the boundary of necrotic lesions in osteonecrosis of the femoral head (ONFH) and to explore its diagnostic value in predicting bone collapse of the femoral head. A retrospective cross-sectional study was conducted in our institution, and 146 hips (121 cases) identified as ONFH were recruited. The anterior and lateral boundaries of each enrolled subject were measured in standard anteroposterior (AP) view and frog-leg (FL) view of plain radiographic images, the intact rate of which was then calculated and presented as the anteroposterior view intact ratio (APIR) and frog-leg view intact ratio (FLIR), respectively. Univariate and multivariate logistic regression analyses were performed to identify risk factors for collapse. A receiver operating characteristic (ROC) curve analysis was performed to determine the sensitivity, specificity and cutoff value of the APIR and FLIR. A Kaplan–Meier (K-M) analysis was applied to calculate the survival rate of the femoral head, and bone collapse of the femoral head was regarded as the endpoint. Femoral head collapse was observed in 61 hips during the follow-up period. Patients with or without femoral head collapse were categorized into the collapse group and non-collapse group, respectively. The mean follow-up time was 3.7 years (2–9) for the collapse group and 7.7 years (5–20) for the non-collapse group. Univariate and multivariate logistic regression analysis and ROC analysis showed that APIR (

The sclerotic zone in the osteonecrosis of femoral head (ONFH), containing condensed trabecular bone and abundant neovascularization, is the transition area between osteonecrosis and normal tissue. Due to the prominent feature in ONFH, the characteristics of the sclerotic zone might indicate the femoral head survival of the disease. Thirty ONFH patients (41 hips) with ring-shaped sclerotic zone at Association Research Circulation Osseous-II were recruited during 1996 to 2019, and the corresponding radiographic images in their follow-up are reviewed retrospectively. Two subtypes (type A and B) are defined to discriminate different locations of ring-shaped sclerotic zone in the femoral head (center or subchondral bone plate) in accordance with the radiographic images. The natural history of the enrolled subjects was followed up for average 9 years to record and compare their collapse incidences as well as the progress of hip symptoms. Chi-square test shows that the occurrence rates of symptomatic hip of type A are significantly lower than that of type B and differences between these two groups were significant (P

To explore the novel magnetic resonance imaging techniques, IVIM-DWI and IDEAL-IQ in detecting bone marrow fat and microcirculation in steroid-induced osteonecrosis of the femoral head (SIONFH). In this prospective study, 49 patients (80 hips) with SIONFH taking glucocorticoids and 24 healthy volunteers (48 hips) were recruited and assessed by T1WI, T2WI/fs, IDEAL-IQ and IVIM-DWI. The affected hips, contralateral asymptomatic hips and normal hips, as well as normal, penumbra and necrotic areas in the affected hips, were classified and evaluated. Imaging results were compared with histologic bone sections obtained from SIONFH patients undergoing surgery. The fat fraction (FF) and perfusion fraction (f) differences between groups were analyzed using analysis of variance, the LSD t-test, Pearson correlation analysis and ROC curve analysis. Our results demonstrate that IDEAL-IQ (FF) and IVIM-DWI (f) enable the classification of SIONFH at different ARCO stages. The FF was positively associated with the progression of the disease (r = 0.72), in contrast to f (r = −0.17). The FF and f were significantly different among the necrotic, penumbra and normal areas, and they were negatively correlated with each other (r = −0.37). The diagnostic sensitivity and specificity of IDEAL-IQ were 96.9% and 86.7%, and those of IVIM-DWI were 72.34% and 58.33%, respectively. The FF in contralateral asymptomatic hips was significantly higher than in normal hips, but no difference was found for f. IDEAL-IQ, and not IVIM-DWI, was identified to successfully detect bone marrow fat, which is beneficial to the diagnosis of the severity of SIONFH.

Aims The aim of this study was to report the medium-term outcomes of impaction bone allograft and fibular grafting for osteonecrosis of the femoral head (ONFH) and to define the optimal indications. Methods A total of 67 patients (77 hips) with ONFH were enrolled in a single centre retrospective review. Success of the procedure was assessed using the Harris Hip Score (HHS) and rate of revision to total hip arthroplasty (THA). Risk factors were studied, including age, aetiology, duration of hip pain, as well as two classification systems (Association Research Circulation Osseous (ARCO) and Japanese Investigation Committee (JIC) systems). Results After a mean follow-up period of 8.61 years (SD 1.45), 81.3% (52/64) of enrolled cases had a good or excellent HHS at latest follow-up (declining to 76.0% (38/50) for those with more than eight years of follow-up). Overall survival was 92.1% at eight years’ follow-up (95% CI 83.2% to 96.4%). A total of 12 hips (19.0%) failed (reoperation or HHS < 70 points) at final follow-up. Rate of success was adversely affected by increasing age, duration of pain, and more severe disease as measured using the ARCO and JIC classifications, but not by aetiology of the ONFH. Conclusion We report favourable medium-term results of this procedure. Best outcomes can be expected in patients matching the following indications: younger than 40 years; less 12-month hip pain before surgery; femoral head collapse being less than 2 mm; and integrated lateral wall of femoral head. Cite this article: Bone Joint J 2020;102-B(7):838–844.

Fracture healing involves a fragile continuum from inflammation to repair and finally ends in bone reestablishment. Fractures that fail to heal progress to a state of nonunion, causing sub-stantial morbidity for the individual. Nonunion is one of the most serious complications of frac-ture. In an updated investigation, the incidence of nonunion in fractures was found to be 1.9%; however, the value can be as high as 9% in specific fracture types, such as tibial and clavicular fractures. Nonunion results in major living and economic burdens on patients and seriously af-fects their mobility. Currently, no effective medical treatments are available to promote fracture repair, and the mainstay of fracture nonunion management is surgery. Infection, ageing, and poor blood supply have been implicated in nonunion. However, the exact mechanism of fracture nonunion is unknown. In recent studies, it has been shown that HGF/c-Met are closely related to the differentia-tion of osteoblasts and osteoclasts, which are the prominent cells responsible for callus for-mation and bone remodelling during fracture repair. Furthermore, hypoxia caused by poor vas-cularization in fracture healing interrupted osteogenesis in vivo and impaired osteoblast and oste-oclast differentiation in vitro. There is also evidence that hypoxia regulates c-Met in many cell types. We hypothesized that hypoxia modulates osteoblast and osteoclast differentiation via c-Met and ultimately causes fracture nonunion. To validate our hypothesis, we performed three types of experiments. First, human bone samples obtained from participants with fracture union and nonunion were collected to determine the expression of c-MET. The results show that c-MET expression is downregulated in fracture nonunion tissues such as callus and the greater trochanter. In serum and bone samples of pa-tients with fracture nonunion, key osteoblastic and osteoclastic markers were also suppressed. To further explore the mechanism of c-Met in the regulation of osteoblasts and osteoclasts, we generated c-Metfl/fl mice possessing loxP sites flanking exon 16 of the c-Met sequence. Re-moving exon 16 results in the loss of the c-Met catalytic domain and the mice are thus knockout mice. We then crossed the c-Metfl/fl mice with Prx1cre mice (to target expression in osteoblast progenitors) or Ctskcre mice (to target expression in osteoclast precursors) and investigated dif-ferences in fracture healing following a proximal femur osteotomy. Our findings suggest that conditional knockout of c-Met in both cell lines does not cause abnormal bone development. However, we observed impaired osteoblast and osteoclast differentiation after birth, subsequent-ly leading to osteopenia (Prx1cre c-Metfl/fl) and increased bone formation (Ctskcre c-Metfl/fl). Knockout of c-Met also delayed the process of fracture healing in the gene-edited mice following fracture surgery. Finally, cell models were established to explore if c-Met regulates osteogenesis under hy-poxic conditions or following treatment with cabozantinib (a c-Met kinase activity inhibitor). Our findings show that hypoxia increases c-Met phosphorylation during the differentiation of MC3T3 (osteoblast progenitors) and RAW264.7 (osteoclast precursors) cells. However, the dif-ferentiation of neither cell type was affected after treatment with cabozantinib. Thus we conclude that enhanced phosphorylation of c-Met in hypoxia is not related to the inhibition of osteoblast and osteoclast differentiation. To summarize, our findings indicate that c-Met is a molecular driver of osteoblast and os-teoclast differentiation and that the knockout of c-Met results in delayed fracture union in mice. In addition, we did not find evidence to link c-Met and hypoxia from tissue ischaemia to im-paired fracture repair.

Serum miRNAs are potential biomarkers for predicting the progress of bone diseases, but little is known about miRNAs in alcohol-induced osteonecrosis of femoral head (AIONFH). This study evaluated disease-prevention value of specific serum miRNA expression profiles in AIONFH. MiRNA PCR Panel was taken to explore specific miRNAs in serum of AIONFH cases. The top differentially miRNAs were further validated by RT-qPCR assay in serum and bone tissues of two independent cohorts. Their biofunction and target genes were predicted by bioinformatics databases. Target genes related with angiogenesis and osteogenesis were quantified by RT-qPCR in necrotic bone tissue. Our findings demonstrated that multiple miRNAs were evaluated to be differentially expressed with high dignostic values. MiR-127-3p, miR-628-3p, and miR-1 were downregulated, whereas miR-885-5p, miR-483-3p, and miR-483-5p were upregulated in serum and bone samples from the AIONFH patients compared to those from the normal control individuals (p IGF2, PDGFA, RUNX2, PTEN, and VEGF, were presumed to be altered in necrotic bone tissue of AIONFH patients. The presence of five altered miRNAs in AIONFH patients may serve as non-invasive biomarkers and potential therapeutic targets for the early diagnosis of AIONFH.

Being the principal cells responsible for bone resorption and pathologic bone loss, osteoclasts have become the main target for antiresorptive treatment. Cumambrin A is a natural compound isolated from Chrysanthemum indicum L. and belongs to a member of the sesquiterpene lactone family. To date, the therapeutic effect of cumambrin A on osteoporosis and its mechanisms of action are not known. In this study, we found that cumambrin A can significantly inhibit osteoclast formation and bone resorption through the suppression of receptor activator of NF-κB ligand (RANKL)-induced NF-κB and nuclear factor of activated T-cell activity and ERK phosphorylation. Furthermore, cumambrin A inhibits the expression of osteoclast marker genes including cathepsin K, calcitonin receptor, and V-ATPase d2. Using an in vivo ovariectomized mouse model, we showed that cumambrin A protects against estrogen withdrawal-induced bone loss. Collectively, our results reveal that cumambrin A can suppress osteoclast formation, bone resorption, and RANKL-induced signaling pathways, suggesting that cumambrin A is a potential therapeutic agent for the treatment of osteoporosis.-Zhou, L., Liu, Q., Hong, G., Song, F., Zhao, J., Yuan, J., Xu, J., Tan, R. X., Tickner, J., Gu, Q., Xu, J. Cumambrin A prevents OVX-induced osteoporosis via the inhibition of osteoclastogenesis, bone resorption, and RANKL signaling pathways.

Background Bernese periacetabular osteotomy (PAO) is an effective treatment for patients with developmental dysplasia of the hip (DDH). PAO has been widely used in China, but few follow-up outcomes have been reported in the international community. Moreover, the risk factors affecting patient-reported outcomes have not been discussed in recent studies. In this study, patient-reported outcomes after PAO were reported, and risk factors affecting patient-reported outcomes were analyzed. Methods Patients who underwent PAO for DDH from January 2014 to January 2020 were selected as the study subjects, and 79 hips were included in the analysis after screening (71 patients, with an average follow-up time of 2.98 years). The Harris Hip Score (HHS) and International Hip Outcome Instrument-12 (iHOT-12) were used to assess hip function and patient quality of life. A HHS 38°, adverse outcomes were much more likely. However, a Tönnis angle of -10°-0 was a protective factor. In addition, hips with fair or poor joint congruency were 7.794-fold more likely to develop negative outcomes. The ROC curve analysis showed that the optimal thresholds for the LCEA and Tönnis angles used to predict outcomes after PAO were 38.1° and − 9°, respectively. The patients with a postoperative LCEA 38.1°. In addition, while the patients with a postoperative Tönnis angle of -9°-0 had a success rate of 70%, and those with a Tönnis angle of 0–10° had a success rate of 65%; the success rate of a Tönnis angle

Background Knee osteoarthritis (KOA), with a high incidence in old-age population, adversely affects their life quality. The valgus knee bracing is an important physical therapy for KOA, but its clinical effects on pain release and functional improvement remained unclear. This meta-analysis is to systematically evaluate the clinical outcomes of valgus knee bracing in patients with KOA. Methods A meta-analysis of clinical randomized controlled trials (RCTs) on pain and functional changes in patients with KOA after using valgus knee braces. The search period was ranged from the inception of the database to May 2020. The enrolled research databases included PubMed, Embase, and Web of Science databases. Two investigators independently formulated inclusion criteria and exclusion criteria and screened and determined the final enrolled literature. Then the outcome indicators were extracted and organized from the included literature, and the risk of bias was assessed by Cochrane Handbook 5.0.1. Results A total of 10 articles were included in this study, including 739 patients. Eight articles were related to the visual analog scale (VAS) pain score, and the results showed that RR = − 0.29, 95% CI − 0.73, 0.15], P = 0.20; four articles were related to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score, and the results showed that RR = − 0.15, 95% CI [− 0.41, 0.11], P = 0.26; two articles were related to the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the results showed that RR = 0.58, 95% CI [− 4.25, 5.42], P = 0.81; and three articles were related to the KOOS Activities of Daily Living (KOOS-ADL), and the results showed that RR = 0.04, 95% CI [− 0.62, 0.69], P = 0.91. These results indicated that the valgus knee bracing has no statistical significance in pain and functional activity improvement of patients with KOA. The subgroup analysis showed that the follow-up time was the source of the heterogeneity of the VAS pain score. Conclusion Our current evidence suggests that valgus knee bracing may not improve pain release and function activates in KOA patients in the long-term period, but only being beneficial to the short-term rehabilitation.

The aim of this study was to report the medium-term outcomes of impaction bone allograft and fibular grafting for osteonecrosis of the femoral head (ONFH) and to define the optimal indications.A total of 67 patients (77 hips) with ONFH were enrolled in a single centre retrospective review. Success of the procedure was assessed using the Harris Hip Score (HHS) and rate of revision to total hip arthroplasty (THA). Risk factors were studied, including age, aetiology, duration of hip pain, as well as two classification systems (Association Research Circulation Osseous (ARCO) and Japanese Investigation Committee (JIC) systems).After a mean follow-up period of 8.61 years (SD 1.45), 81.3% (52/64) of enrolled cases had a good or excellent HHS at latest follow-up (declining to 76.0% (38/50) for those with more than eight years of follow-up). Overall survival was 92.1% at eight years' follow-up (95% CI 83.2% to 96.4%). A total of 12 hips (19.0%) failed (reoperation or HHS70 points) at final follow-up. Rate of success was adversely affected by increasing age, duration of pain, and more severe disease as measured using the ARCO and JIC classifications, but not by aetiology of the ONFH.We report favourable medium-term results of this procedure. Best outcomes can be expected in patients matching the following indications: younger than 40 years; less 12-month hip pain before surgery; femoral head collapse being less than 2 mm; and integrated lateral wall of femoral head. Cite this article

Background/objective: A prospective cohort study aimed to evaluate the clinical efficacy of a specific vasoactive herbal formula, Huo Xue Tong Luo capsule (HXTL capsule), for the treatment of patients with asymptomatic osteonecrosis of femoral head (ONFH). Methods: We evaluated a clinical trial of 55 patients (59 hips) with asymptomatic ONFH (no joint collapse) evaluated by Steinberg staging system and necrosis range classification criteria. Then, they were given HXTL capsule under specific protocol. Among them, 39 males and 16 females with an average age of 36.4 ± 10.1 years were followed up for an average of 4.38 years during treatment. The aggravation of clinical and imaging results was assessed by initial pain and joint collapse. The clinical and imaging outcomes of these patients were compared with those of a historical control group from the literature under critical inclusion criteria. Results: At the latest follow-up, initial pain occurred in five of 59 (8.5%) hips of patients taking HXTL capsule compared with 31 of 81 (38.3%) controls (p

Background In the future, biochemical MRI might provide a valuable noninvasive quantitative analysis of the biochemical composition of cartilage in osteonecrosis of the femoral head (ONFH). Purpose To investigate the diagnostic performance of T1 ρ and T2 mapping in cartilage denaturalization with ONFH and to determine the correlation between T1 ρ and T2 mapping and the Association Research Circulation Osseous (ARCO) stage. Study type Prospective. Subjects Forty-seven patients with ONFH (stage I to III according to the ARCO criteria) and 24 volunteers (control group) were recruited for the prospective study. Sequence Conventional MRI, multiple echo recalled gradient echo (MERGE), and T1 ρ and T2 mapping sequences. Assessment Pseudocolor images and MERGE images were combined in the AW4.5 workstation. The region of interest (ROI) of the hip cartilage was 4-6 mm². The sagittal T1 ρ and T2 mapping values were calculated by the two first authors. Statistical tests One-way analysis of variance (ANOVA), LSD t-tests, Pearson correlation analysis, and receiver operator characteristic (ROC) curves. The significance level was set at P Results The T1 ρ and T2 mapping values of the ONFH group were significantly higher than the values of the control group (P = 0.000). Regarding the assessment of the severity of ARCO staging, both T1 ρ (r = 0.66, P = 0.004) and T2 mapping (r = 0.501, P = 0.002) were positively associated with disease severity. The T1 ρ values were positively correlated with the T2 mapping values (r = 0.381, P = 0.000). The areas under the curve (AUC) for the T1 ρ and T2 mapping values were 0.822 and 0.791, respectively. The diagnostic sensitivity and specificity were 72.34% and 70.83% for T1 ρ mapping and 72.34% and 58.33%, respectively, for T2 mapping. Data conclusion Both T1 ρ and T2 mapping performed well in diagnosing the cartilage denaturalization in ARCO stage I-III ONFH patients. T1 ρ mapping had a higher diagnostic sensitivity and specificity than T2 mapping. Level of evidence 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:760-767.

Identification of natural compounds that inhibit osteoclastogenesis will facilitate the development of antiresorptive treatment of osteolytic bone diseases. Asiaticoside is a triterpenoid derivative isolated from Centella asiatica, which exhibits varying biological effects like angiogenesis, anti-inflammation, wound healing, and osteogenic differentiation. However, its role in osteoclastogenesis remains unknown. Here, we show that Asiaticoside can suppress RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner. Asiaticoside attenuated the expression of osteoclast marker genes including Ctsk, Atp6v0d2, Nfatc1, Acp5, and Dc-stamp. Furthermore, Asiaticoside inhibited RANKL-mediated NF-κB and NFATc1 activities, and RANKL-induced calcium oscillation. Collectively, this study demonstrates that Asiaticoside inhibited osteoclast formation and function through attenuating RANKL-induced key signaling pathways, which may indicate that Asiaticoside is a potential antiresorptive agent against osteoclast-related osteolytic bone diseases.

Epidermal growth factor-like domain-containing protein 7 (EGFL7), a member of the epidermal growth factor (EGF)-like protein family, is a potent angiogenic factor expressed in many different cell types. EGFL7 plays a vital role in controlling vascular angiogenesis during embryogenesis, organogenesis, and maintaining skeletal homeostasis. It regulates cellular functions by mediating the main signaling pathways (Notch, integrin) and EGF receptor cascades. Accumulating evidence suggests that Egfl7 plays a crucial role in cancer biology by modulating tumor angiogenesis, metastasis, and invasion. Dysregulation of Egfl7 has been frequently found in several types of cancers, such as malignant glioma, colorectal carcinoma, oral and oesophageal cancers, gastric cancer, hepatocellular carcinoma, pancreatic cancer, breast cancer, lung cancer, osteosarcoma, and acute myeloid leukemia. In addition, altered expression of miR-126, a microRNA associated with Egfl7, was found to play an important role in oncogenesis. More recently, our study has shown that EGFL7 is expressed in both the osteoclast and osteoblast lineages and promotes endothelial cell activities via extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), and integrin signaling cascades, indicative of its angiogenic regulation in the bone microenvironment. Thus, understanding the role of EGFL7 may provide novel insights into the development of improved diagnostics and therapeutic treatment for cancers and skeletal pathological disorders, such as ischemic osteonecrosis and bone fracture healing.

Sclerostin is an osteocyte-derived protein that has a potent inhibitory effect on osteoblast activity. The osteocyte apoptosis induced by various causes of osteonecrosis of the femoral head (ONFH) plays a key role in the promotion of femoral head collapse. But the effect of altering sclerostin level on the collapse of ONFH has not been studied. Our aim was to assess the role of sclerostin level in the collapse of ONFH. Between May 2016 and November 2016, 236 subjects were enrolled in the present study. The patients were classified according to the Association Research Circulation Osseous (ARCO) classification. The clinical bone histomorphology, the expression position, and level of sclerostin as well as the plasma sclerostin level were evaluated. The sclerostin level was significantly lower in the non-traumatic ONFH group than those in the healthy control group (P = 0.002). The sclerostin level was negatively associated with ARCO stages (r = − 0.239, P = 0.009) and significantly lower in the postcollapse group (P = 0.025). The reduced expression of sclerostin may play a key role in the collapse process of ONFH and be predictive of the disease progression of ONFH.

Osteoporosis is a disease characterized by abnormally increased formation and function of osteoclasts. Anti-RANKL treatment using natural medicine is a potential therapy for osteoporosis. Here, we studied the effect of fangchinoline, which is extracted from the root of Stephania tetrandra S. Moore, on osteoclast formation and function. We found that fangchinoline inhibited osteoclastogenesis at doses of 0.5 and 1 µM. In addition, we also examined the mechanism of the inhibitory effect of fangchinoline on osteoclasts. We found that fangchinoline down regulated NFATc1 activity and expression. However, fangchinoline did not affect IκBα degradation and MAPK pathways. In addition, we also found that fangchinoline could protect against bone loss in OVX mice. Taken together, fangchinoline may be a potential compound for osteoporosis.

Excessive bone resorption by osteoclasts plays an important role in osteoporosis. Bone loss occurs in ovariectomised (OVX) mice in a similar manner to that in humans, so this model is suitable for evaluating potential new therapies for osteoporosis. Neohesperidin (NE) is a flavonoid compound isolated from citrus fruits. Its role in bone metabolism is unknown. In this study we found that neohesperidin inhibits osteoclast differentiation, bone resorption and the expression of osteoclast marker genes, tartrate-resistant acid phosphatase and cathepsin K. In addition, neohesperidin inhibited receptor activator of NF-κB ligand (RANKL)-induced activation of NF-κB, and the degradation of inhibitor of kappa B-alpha (IκBα). Furthermore, neohesperidin inhibited RANKL induction of nuclear factor of activated T-cells (NFAT) and calcium oscillations. In vivo treatment of ovariectomised mice with neohesperidin protected against bone loss in mice. The results suggest neohesperidin has anti-osteoclastic effects in vitro and in vivo and possesses therapeutic potential as a natural anti-catabolic treatment in osteoporosis.

Icariin, the main effective component of Herba Epimedii, has been identified to regulate the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and have potential application in preventing bone loss and promoting bone regeneration. However, the underlying signaling pathway of its osteogenic effect remains unclear. Here, we investigated whether icariin could promote osteogenesis of rBMSCs through modulating the estrogen receptor alpha (ERα) and Wnt/β-catenin signaling pathways, which implicated in rBMSCs osteogenesis. rBMSCs were cultured in osteogenic induction medium and treated with icariin or together with ICI 182780 or DKK1, the effects on the expression of osteogenic genes and Wnt/β-catenin signaling were detected. Results indicated that icariin (0.1μM) markedly enhanced the proliferation of rBMSCs and alkaline phosphatase (ALP) activity. Additionally, icariin (0.1μM) significantly up-regulated the expression of osteogenic genes (Runx2, osteopotin, DLX5, osteocalcin, collagen type I, and ERα) and Wnt signal members (β-catenin, Lef1, TCF7, c-jun, c-myc, and cyclin D). Furthermore, icariin stimulated the activation of β-catenin as evidenced by increased total β-catenin protein and nuclear translocation. These osteogenesis-potentiating effects of icariin were blocked by ICI 182780 or DKK1. Taken together, these results suggest that the osteogenic effects of icariin on rBMSCs involves the ERα-Wnt/β-catenin signaling pathway.

Microrchidia (MORC or MORC family CW-type zinc finger protein), a highly conserved nuclear protein superfamily, is an interesting new player in signaling-dependent chromatin remodeling and epigenetic regulation. MORC family proteins consist of MORC1, MORC2, MORC3, and MORC4 which display common structural determinants such as CW-type zinc finger and coiled-coil domains. They also exhibit unique structural motifs and tissue-specific expression profiles. MORC1 was first discovered as a key regulator for male meiosis and spermatogenesis. Accumulating biochemical and functional analyses unveil MORC proteins as key regulators for cancer development. More recently, using an ENU mutagenesis mouse model, MORC3 was found to play a role in regulating bone and calcium homeostasis. Here we discuss recent research progress on the emerging role of MORC proteins in cancer development and bone metabolism. Unravelling the cellular and molecular mechanisms by which MORC proteins carry out their functions in a tissue specific manner are important subjects for future investigation. J. Cell. Physiol. 232: 928-934, 2017. © 2016 Wiley Periodicals, Inc.

Bone marrow stromal cells (BMSCs) have proven to be useful for the treatment of numerous human diseases. However, the reparative ability of BMSCs is limited by their poor migration. Polydatin, widely used in traditional Chinese remedies, has proven to exert protective effects to BMSCs. However, little is known about its role in BMSCs migration. In this study, we studied the effects of polydatin on rat BMSCs migration using the scratch wound healing and transwell migration assays. Our results showed polydatin could promote BMSCs migration. Further experiments showed activation of ERK 1/2, but not JNK, was required for polydatin-induced BMSCs migration, suggesting that polydatin may promote BMSCs migration via the ERK 1/2 signaling pathways. Taken together, our results indicate that polydatin might be beneficial for stem cell replacement therapy by improving BMSCs migration.

PCR reactions used specific primers of the genes. The table provides the information of PCR reactions used specific primers of mRNAs detected in our research, including Runt Related Transcription Factor 2 (RUNX2), Osteocalcin (BGLAP), β-catenin (CTNNB1), Bone Morphogenetic Protein 2 (BMP2) were detected. In Strategy two, the mRNAs of osteogenic genes, including RUNX2, Distal-less Homeobox 5 (DLX5), Osteopontin (SPP1), Collagen type I (COL1), BGLAP and BMP2, and Wnt/β-catenin target genes, including CTNNB1, Transcription Factor 7 (TCF7), Lymphoid Enhancer Binding Factor 1 (LEF1), MYC (C-MYC), cyclin D (CCND1) and c-JUN (JUN). (DOCX 15 kb)

Appendix 1. Search strategy: PubMed. Appendix 2. Oxford Centre for Evidence-based Medicineâ Levels of Evidence (March 2009). Appendix 3. Quality evaluation of included studies case series studies. (DOCX 33 kb)

Background Osteonecrosis of the femoral head was gradually concerned as a global disease for its progression to collapse of the femoral head, ultimately causing the arthritic change. Due to the high incidence of this disease in young people, arthroplasty tends to be suspected for its uncertain long-term efficiency. Vascularized pedicle iliac bone grafts, as a hip-preserving surgery, were regarded as an effective option in hip-preserving protocol since the 1970s. Nevertheless, there exist no unified standards widely agreed as the optimal operative program since the lack and heterogeneity of related studies. Thus, we execute this systematic review to synthesize and analyze existing studies, and further suggest a direction of future researches. Methods Data were collected by searching electronic database (PubMed, Embase, and Cochrane Library) and including the eligible studies of all types of clinical researches except case report. Through our extraction and synthesis of included study results in respect of clinical evaluation (rating scales), radiographic evaluation, joint survival rate, viability of implanted flap, and complications by transform varied assessment method into a unified standard, we qualitatively analyze and discuss the efficacy of VPIBG according to the quality of individual study and the heterogeneity across the included studies. Results Our systematic review includes 1 RCT, 2 case-control studies, and 13 case series studies, resulting in a significant improvement of postoperative scores. Minority of hips progressed for joint replacement. Some researches suggested a high collapse rate in the collapsed femoral head before the operation. Compared with some other hip-preserving surgeries, the complications of VPIBG are relatively slight and barely affect clinical efficiency. Conclusions A better clinic response was obtained after this treatment, especially in femoral heads before the appearance of a crescent sign. The fixation of the implanted iliac bone flap increases the clinical effect. The majority of complications were slight and rarely affected clinical efficacy. Electronic supplementary material The online version of this article (10.1186/s13018-019-1262-2) contains supplementary material, which is available to authorized users.

In the future, biochemical MRI might provide a valuable noninvasive quantitative analysis of the biochemical composition of cartilage in osteonecrosis of the femoral head (ONFH).To investigate the diagnostic performance of TProspective.Forty-seven patients with ONFH (stage I to III according to the ARCO criteria) and 24 volunteers (control group) were recruited for the prospective study.Conventional MRI, multiple echo recalled gradient echo (MERGE), and TPseudocolor images and MERGE images were combined in the AW4.5 workstation. The region of interest (ROI) of the hip cartilage was 4-6 mm². The sagittal TOne-way analysis of variance (ANOVA), LSD t-tests, Pearson correlation analysis, and receiver operator characteristic (ROC) curves. The significance level was set at P0.05.The TBoth T2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:760-767.

Disc nucleus pulposus (NP) matrix homeostasis is important for normal disc function. Mechanical overloading seriously decreases matrix synthesis and increases matrix degradation. The present study aims to investigate the effects of resveratrol on disc NP matrix homeostasis under a relatively high-magnitude mechanical compression and the potential mechanism underlying this process. Porcine discs were perfusion-cultured and subjected to a relatively high-magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days in a mechanically active bioreactor. The non-compressed discs were used as controls. Resveratrol was added along with culture medium to observe the effects of resveratrol on NP matrix synthesis under mechanical load respectively. NP matrix synthesis was evaluated by histology, biochemical content (glycosaminoglycan (GAG) and hydroxyproline (HYP)), and expression of matrix macromolecules (aggrecan and collagen II). Results showed that this high-magnitude mechanical compression significantly decreased NP matrix content, indicated by the decreased staining intensity of Alcian Blue and biochemical content (GAG and HYP), and the down-regulated expression of NP matrix macromolecules (aggrecan and collagen II). Further analysis indicated that resveratrol partly stimulated NP matrix synthesis and increased activity of the PI3K/Akt pathway in a dose-dependent manner under mechanical compression. Together, resveratrol is beneficial for disc NP matrix synthesis under mechanical overloading, and the activation of the PI3K/Akt pathway may participate in this regulatory process. Resveratrol may be promising to regenerate mechanical overloading-induced disc degeneration.

Microrchidia (MORC or MORC family CW-type zinc finger protein), a highly conserved nuclear protein superfamily, is an interesting new player in signaling-dependent chromatin remodeling and epigenetic regulation. MORC family proteins consist of MORC1, MORC2, MORC3, and MORC4 which display common structural determinants such as CW-type zinc finger and coiled-coil domains. They also exhibit unique structural motifs and tissue-specific expression profiles. MORC1 was first discovered as a key regulator for male meiosis and spermatogenesis. Accumulating biochemical and functional analyses unveil MORC proteins as key regulators for cancer development. More recently, using an ENU mutagenesis mouse model, MORC3 was found to play a role in regulating bone and calcium homeostasis. Here we discuss recent research progress on the emerging role of MORC proteins in cancer development and bone metabolism. Unravelling the cellular and molecular mechanisms by which MORC proteins carry out their functions in a tissue specific manner are important subjects for future investigation. J. Cell. Physiol. 232: 928-934, 2017. © 2016 Wiley Periodicals, Inc.

Pathological osteolysis is commonly associated with osteoporosis, bone tumors, osteonecrosis, and chronic inflammation. It involves excessive resorption of bone matrix by activated osteoclasts. Suppressing receptor activator of NF-κB ligand (RANKL) signaling pathways has been proposed to be a good target for inhibiting osteoclast differentiation and bone resorption. Bajijiasu—a natural compound derived from Morinda officinalis F. C. How—has previously been shown to have anti-oxidative stress property; however, its effect and molecular mechanism of action on osteoclastogenesis and bone resorption remains unclear. In the present study, we found that Bajijiasu dose-dependently inhibited RANKL-induced osteoclast formation and bone resorption from 0.1 mM, and reached half maximal inhibitory effects (IC50) at 0.4 mM without toxicity. Expression of RANKL-induced osteoclast specific marker genes including cathepsin K (Ctsk), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAcP), vacuolar-type H+-ATPase V0 subunit D2 (V-ATPase d2), and (matrix metalloproteinase-2 (MMP2) was inhibited by Bajijiasu treatment. Luciferase reporter gene studies showed that Bajijiasu could significantly reduce the expression and transcriptional activity of NFAT as well as RANKL-induced NF-κB activation in a dose-dependent manner. Further, Bajijiasu was found to decrease the RANKL-induced phosphorylation of extracellular signal-regulated kinases (ERK), inhibitor of κB-α (IκB-α), NFAT, and V-ATPase d2. Taken together, this study revealed Bajijiasu could attenuate osteoclast formation and bone resorption by mediating RANKL signaling pathways, indicative of a potential effect of Bajijiasu on osteolytic bone diseases.