Exosomal SPRY4 from adipogenic BMSCs impairs angiogenesis via the PTPRB/TIE2/PI3K axis in Steroid-induced osteonecrosis of the femoral head.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Steroid-induced osteonecrosis of the femoral head (SONFH) drives irreversible bone collapse, yet current therapies inadequately target the disrupted angiogenic-osteogenic coupling central to its pathogenesis. Although pathological adipocyte hyperplasia is a hallmark of SONFH, the mechanisms by which adipogenic bone marrow mesenchymal stem cells (BMSCs) suppress angiogenesis remain unresolved. Emerging evidence implicates exosomes as mediators of adipose-vascular crosstalk, yet their role in SONFH-associated vasculopathy remains unexplored. Here, we elucidate how adipogenic BMSCs impair angiogenesis in SONFH through exosomal delivery of SPRY4. Adipogenic BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. RT-PCR was employed to assess the expression of angiogenic genes. Transwell and wound healing assays were conducted to evaluate the migratory capacity of HUVECs. Tube formation assays were performed to investigate HUVEC angiogenesis. RNA sequencing (RNAseq) was utilized to identify potential regulatory factors within exosomes derived from adipogenic BMSCs. The target relationship between SPRY4 and PTPRB was predicted and validated through co-immunoprecipitation and mass spectrometry. Western blotting (WB) was used to confirm the signaling pathway involved in SPRY4-mediated angiogenesis disorders. Hematoxylin and eosin (HE) staining and immunohis

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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