Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppresso

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)

Background Local ischemia and defective osteogenesis are implicated in the progression of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Recent studies have revealed that exosomes released from adipose-derived stem cells (ASCs) play important roles in ONFH therapy. The present study aimed to investigate whether exosomes derived from miR-378-overexpressing ASCs (miR-378-ASCs-Exos) could promote angiogenesis and osteogenesis in GC-induced ONFH. Methods In vitro, we investigated the osteogenic potential of miR-378-ASCs-Exos on bone marrow stromal cells (BMSCs) by alkaline phosphatase staining and western blotting. The angiogenic effects of miR-378-ASCs-Exos on human umbilical vein endothelial cells (HUVECs) were examined by evaluating their proliferation, migration, and tube-forming analyses. We identified the underlying mechanisms of miR-378 in osteogenic and angiogenic regulation. In addition, an ONFH rat model was established to explore the effects of miR-378-ASCs-Exos through histological and immunohistochemical staining and micro-CT in vivo. Results Administration of miR-378-ASCs-Exos improved the osteogenic and angiogenic potentials of BMSCs and HUVECs. miR-378 negatively regulated the suppressor of fused (Sufu) and activated Sonic Hedgehog (Shh) signaling pathway, and recombinant Sufu protein reduced the effects triggered by miR-378-ASCs-Exos. In vivo

Evidence level

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

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