SCUBE3 promotes osteogenic differentiation and mitophagy in human bone marrow mesenchymal stem cells through the BMP2/TGF-ß signaling pathway.

In clinical settings, addressing large bone defects remains a significant challenge for orthopedic surgeons. The use of genetically modified bone marrow mesenchymal stem cells (BMSCs) has emerged as a highly promising approach for these treatments. Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) is a multifunctional secreted glycoprotein, the role of which remains unclear in human hBMSCs. This study used various experimental methods to elucidate the potential mechanism by which SCUBE3 influences osteogenic differentiation of hBMSCs in vitro. Additionally, the therapeutic efficacy of SCUBE3, in conjunction with porous GeLMA microspheres, was evaluated in vivo using a mouse bone defect model. Our findings indicate that SCUBE3 levels increase significantly during early osteogenic differentiation of hBMSCs, and that reducing SCUBE3 levels can hinder this differentiation. Overexpressing SCUBE3 elevated osteogenesis gene and protein levels and enhanced calcium deposition. Furthermore, treatment with recombinant human SCUBE3 (rhSCUBE3) protein boosted BMP2 and TGF-ß expression, activated mitophagy in hBMSCs, ameliorated oxidative stress, and restored osteogenic function through SMAD phosphorylation. In vivo, GELMA/OE treatment effectively accelerated bone healing in mice. In conclusion, SCUBE3 fosters osteogenic differentiation and mitophagy in hBMSCs by activating the BMP2/TGF-ß signaling pathway. When combined with engineered hydrogel cell therapy, it could offer valuable guidance for the clinical management of extensive bone defects.

Comparing surgical interventions for intertrochanteric hip fracture by blood loss and operation time: a network meta-analysis.

BACKGROUND: Multiple operative treatments are available for the fixation of intertrochanteric femoral fractures. This analysis was conducted to provide guidance on the appropriate clinical choice to accommodate individual patients. METHODS: A systematic review was performed to identify relevant articles in databases. Randomized controlled trials (RCTs) of adults with intertrochanteric femoral fractures were eligible if they compared 2 or more of the following interventions: proximal femoral nail anti-rotation (PFNA), percutaneous compression plate (PCCP) use, dynamic hip screw (DHS) fixation, gamma nail (GN) fixation, and artificial femoral head replacement (FHR). Bayesian network meta-analysis was performed to simultaneously compare all treatment methods. RESULTS: In total, 24 active-comparator studies involving 3097 participants were identified. Across all populations, greater reductions in blood loss and operation time were observed for PFNA than for other treatments. In terms of bleeding, more blood loss was observed for DHS use than for the PFNA (SMD, 1.96; 95% CI, 1.01-1.96), PCCP (SMD, 1.26; 95% CI, 0.31-2.20), and GN (SMD, 0.26; 95% CI, - 0.35-0.87) techniques. However, a more beneficial effect was observed for DHS use than for FHR (SMD, - 0.23; 95% CI, - 1.26-0.81). DHS use resulted in a significantly longer duration of operation time than the PFNA (SMD, 0.75; 95% CI, - 0.02-0.75), PCCP (SMD, 0.61; 95% CI, - 0.20-1.44), and GN (SMD, 0.25; 95% CI, - 0.26-0.77) techniques. Similarly, greater reductions in operation time were observed for DHS use than for FHR (SMD, - 0.12; 95% CI, - 1.15-0.91). CONCLUSIONS: The findings provide supporting evidence demonstrating the superiority of PFNA over other treatments for intertrochanteric femoral fracture. PFNA treatment results in the lowest amount of blood loss and the shortest operation time. These findings add to the existing knowledge of intertrochanteric femoral fracture treatment options.