This meta-analysis was performed to determine the efficacy of suprapatellar versus infrapatellar approach for tibia intramedullary nailing (IMN). A systematic search was performed in PubMed, Embase, Cochrane library, CNKI and Wanfang. Cochrane collaboration's tool and the Newcastle-Ottawa scale were used to evaluate literature qualities. Meta-analysis was performed using RevMan 5.3 software. Eight studies were eligible, including two randomized controlled trials (RCTs) and six retrospective cohort trials. There were no significant differences between suprapatellar and infrapatellar approaches in operation time, coronal plane alignment, and incidence of postoperative deep infection, nonunion and secondary operation. However, suprapatellar nailing achieved a significant shorter fluoroscopy time, less VAS pain score, better sagittal plane alignment and lower incidence of angular malalignment. Though pooled results indicated no significant difference in terms of final follow-up knee functional score, the RCT subgroup analysis showed that a higher knee functional score existed in suprapatellar group. For tibia IMN, suprapatellar approach might be superior to infrapatellar approach with shorter fluoroscopy time, less knee pain, better knee function recovery, and more accurate fracture reduction. Meanwhile, no increased risk of postoperative complications was identified. More RCTs are required for further research.

Microenvironmental conditions can influence the differentiation and functional roles of mesenchymal stem cells (MSCs). Recent studies have suggested that an inflammatory microenvironment can significantly affect the osteogenic differentiation of MSCs. Here, we show, for the first time, that IL‐10 has concentration‐dependent, dual roles in the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs). Low physiologic concentrations of IL‐10 (0.01–1.0 ng/ml) activate the p38/MAPK signaling pathway to promote the osteogenesis of hBMSCs, but higher pathologic doses of IL‐10 (10–100 ng/ml) inhibit p38/MAPK signaling by activating NF‐κB, inhibiting osteogenesis. These results demonstrate that p38/MAPK and NF‐κB signaling mediates the double‐edged sword effect of IL‐10 on hBMSCs. The osteogenic impairment was reversed at higher doses of IL‐10 when cells were supplemented with the NF‐κB inhibitor BAY11–7082. These data provide important insights into the regulatory effects of IL‐10 on the biologic behavior of hBMSCs.—Chen, E., Liu, G., Zhou, X., Zhang, W., Wang, C., Hu, D., Xue, D., Pan, Z. Concentration‐dependent, dual roles of IL‐10 in the osteogenesis of human BMSCs via P38/MAPK and NF‐κB signaling pathways. FASEB J. 32, 4917–4929 (2018). www.fasebj.org

Sirtuin 7 (SIRT7) is a NAD⁺-dependent deacetylase in the sirtuin family. In a previous study, human bone marrow mesenchymal stem cells (hBMSCs) with reduced SIRT7 activity were developed to evaluate the effect of SIRT7 on osteogenesis. SIRT7 knockdown significantly enhanced osteoblast-specific gene expression, alkaline phosphatase activity, and mineral deposition in vitro. Additionally, SIRT7 knockdown upregulated β-catenin. The enhanced osteogenesis due to SIRT7 knockdown was partially rescued by a Wnt/β-catenin inhibitor. Furthermore, SIRT7 knockdown hBMSCs combined with a chitosan scaffold significantly promoted bone formation in a rat tibial defect model, as determined by imaging and histological examinations. These findings suggest that SIRT7 has an essential role in osteogenic differentiation of hBMSCs, partly by activation of the Wnt/β-catenin signaling pathway.

Management of fracture healing with a large bone defect remains a tricky subject in orthopedic trauma. Enhancing osteogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs) is one of the useful therapeutic strategies for fracture healing. Previous studies have revealed that Apelin may play an important role in bone metabolism. However, its function in the osteogenesis of hBMSCs remains unclear. Therefore, in this study, we investigated the effects and mechanism of Apelin on osteogenic differentiation. We investigated the osteogenesis effects of hBMSCs by both exogenous Apelin protein and overexpression Apelin in vitro. Cell proliferation assay was used to assess the effect of Apelin on the proliferation of hBMSCs. ALP staining and Alizarin Red staining were used to evaluate ALP activity and mineral deposition respectively. qPCR and Western blotting analysis were used to detect the expression of target genes and proteins. In vivo, a rat tibial osteotomy model was established; radiographic analysis and histological evaluation were used to confirm the therapeutic effects of Apelin in fracture healing. Statistical significance was determined by two-tailed Student’s t test when 2 groups were compared. When more than 2 groups were compared, one-way ANOVA followed by Bonferroni’s post-hoc test was used. And two-way ANOVA, followed by Bonferroni multiple comparisons post-hoc test, was performed when the treatment groups at different time points were compared. The addition of exogenous Apelin protein or overexpression of Apelin promoted osteoblast differentiation of hBMSCs in vitro. Increased mineral deposits were observed after treatment with extracellular Apelin protein or after the upregulation of Apelin. Moreover, β-catenin levels were upregulated by Apelin. The enhancement of osteogenic differentiation induced by Apelin was attenuated by specific Wnt/β-catenin signaling pathway inhibitors. In a rat tibial osteotomy model, local injection of exogenous Apelin protein improved bone healing, as demonstrated by imaging and histological analyses. Taken together, these findings indicate that Apelin regulates osteogenic differentiation of hMSCs partly via the Wnt/β-catenin signaling pathway and effectively promotes fracture healing.

Osteoarthritis is a degenerative joint disorder characterized by cartilage degradation, synovial inflammation, and altered subchondral bone structure. Recent insights have identified mitochondrial dysfunction as a pivotal factor in OA pathogenesis, contributing to chondrocyte apoptosis, oxidative stress, and extracellular matrix degradation. Disruptions in mitochondrial dynamics, including impaired biogenesis, mitophagy, and metabolic shifts from oxidative phosphorylation to glycolysis, exacerbate cartilage damage by promoting the production of reactive oxygen species and matrix-degrading enzymes such as ADAMTS and MMPs. This review explores the molecular mechanisms underlying mitochondrial dysfunction in OA, emphasizing its role in cartilage homeostasis and inflammation. Furthermore, it highlights emerging therapeutic strategies targeting mitochondrial pathways, including antioxidants, mitophagy enhancers, and metabolic modulators, as potential interventions to mitigate disease progression, which offer promising avenues for advancing personalized and disease-modifying treatments in OA.