The current evidence suggests that periarticular multimodal drug injection in TKA provides short-term advantages in pain relief, straight leg raise and postoperative complications.

The subvastus and medial parapatellar approaches are 2 commonly performed techniques in total knee arthroplasty, but the optimal approach for total knee arthroplasty remains controversial. The purpose of this study was to compare the effectiveness and safety of the subvastus vs medial parapatellar approach.The PubMed, Embase, Cochrane Library, Inter-Services Intelligence Web of Knowledge, and Chinese Biomedical Literature databases were searched for eligible quasi-randomized, controlled and randomized, controlled trials. Two authors independently extracted data and assessed the methodological quality of the included studies according to the Cochrane handbook version 5.1.0. Statistical analysis was performed using Review Manager version 5.1 software. Eight randomized, controlled trials and 1 quasi-randomized, controlled trial involving 940 primary total knee arthroplasties were included for meta-analysis. Meta-analysis revealed significant differences favoring the subvastus group in Knee Society Score in terms of function at 4 to 6 weeks (weighted mean difference [WMD]=5.09; 95% confidence interval [CI], 3.08 to 7.09; P<.01) and knee score at 12 months (WMD=2.17; 95% CI, 0.01 to 4.34; P=.05) and lateral retinacular release (odds ratio=0.34; 95% CI, 0.14 to 0.79; P=.01) when compared with the medial parapatellar approach. However, both groups showed similar results in range of motion (P>.05), operative time (WMD=2.15; 95% CI, -3.61 to 7.35; P=.42), blood loss (WMD= -31.07; 95% CI, -91.89 to 29.75; P=.32), hospital stay (WMD= -0.18; 95% CI, -0.67 to 0.31; P=.47), and postoperative complications (P>.05).

Exosomes derived from mesenchymal stem cells (MSCs) have emerged as significant mediators of intercellular communication, with studies highlighting their role in the transmission of biological signals between cells. Dominant microRNA (miRNA)-mediated translational repression of messenger RNAs has been extensively investigated in regard to its influence in orchestrating osteogenic differentiation. In the current study, we sought to ascertain the contributory role of miRNA-101 (miR-101) encapsulated in the process of bone marrow mesenchymal stem cell (BMSC)-derived exosomes in osteogenic differentiation. Exosomes were initially extracted from BMSCs at Days 0, 3, 12, and 21 of osteogenic differentiation by ultracentrifugation. Artificial modulation of miR-101 and FBXW7 (silencing and overexpression) were performed in the BMSCs to identify its effects on osteogenic factors, alkaline phosphatase activity, and osteogenic differentiation. Mechanistic exploration was performed to evaluate the binding affinity between miR-101 and FBXW7, the FBXW7-mediated HIF1α ubiquitination, and the HIF1α enrichment in the FOXP3 promoter region. Exosomes from MSCs in the late stage of osteogenic differentiation exhibited enhanced osteogenic differentiation. Upregulated miR-101 in MSC-derived exosomes was detected during osteogenic differentiation, while diminished levels of FBXW7 expression was noted. Importantly, miR-101 was found to specifically bind to the 3′-untranslated region of FBXW7. Meanwhile, data was obtained indicating that FBXW7 could ubiquitinate and degrade HIF1α to repress its upregulation during osteogenic differentiation. HIF1α bound to the promoter region of FOXP3 to facilitate osteogenic differentiation. Ultimately, the findings of the current study demonstrate that BMSC-derived exosomal miR-101 augments osteogenic differentiation in MSCs by inhibiting FBXW7 to regulate the HIF1α/FOXP3 axis.

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Background Osteogenic differentiation is an essential process for bone regeneration involving bone marrow mesenchymal stem cells (BMSCs). BMSC-secreted extracellular vesicles (EVs) enriched with microRNAs (miRs) have vital roles to play in mediating osteogenic differentiation. Therefore, this study aimed to explore the effect of BMSC-derived EVs loaded with miR-15b on osteogenic differentiation. Methods Human BMSCs (hBMSCs) were cultured and treated with plasmids overexpressing or knocking down KLF2, WWP1, and miR-15b to define the role of derived EVs in osteogenic differentiation in vitro. The expression of osteogenic differentiation-related marker was measured by Western blot analysis. The interaction among miR-15b, WWP1, and ubiquitination of KLF2 was investigated by dual-luciferase reporter, immunoprecipitation, and GST pull-down assays. Moreover, EVs from hBMSCs transfected with miR-15b inhibitor (EV-miR-15b inhibitor) were injected into ovariectomized rats to verify the effect of miR-15b on bone loss in vivo. Results WWP1 was downregulated, and KLF2 was upregulated during osteogenic differentiation. After co-culture with EVs, miR-15b expression was elevated and WWP1 expression was reduced in hBMSCs. Upregulation of miR-15b or KLF2 or downregulation of WWP1 or NF-κB increased ALP activity and cell mineralization, as well as osteogenic differentiation-related marker expression in hBMSCs. Mechanistically, miR-15b targeted and inhibited WWP1, thus attenuating KLF2 degradation and inhibiting NF-κB activity. Co-culture of EVs increased the bone volume and trabecular number, but decreased bone loss in ovariectomized rats, which could be reversed after treatment with EV-miR-15b inhibitor. Conclusion Collectively, BMSC-derived EVs loaded with miR-15b promoted osteogenic differentiation by impairing WWP1-mediated KLF2 ubiquitination and inactivating the NF-κB signaling pathway. Graphical abstract