The opposite functions of miR‐24 in the osteogenesis and adipogenesis of adipose‐derived mesenchymal stem cells are mediated by the HOXB7/β‐catenin complex

다국어 초록 (Multilingual Abstract)

Adipose‐derived mesenchymal stem cells (ADMSCs) used in combination with nanoparticles or scaffolds represent promising candidates for bone engineering. Compared to bone marrow‐derived MSCs (BMMSCs), ADMSCs show a relatively low capacity for osteogenesis. In the current study, miR‐24 was identified as an osteogenesis‐ and adipogenesis‐related miRNA that performs opposing roles (inhibition in osteogenesis and promotion in adipogenesis) during these two differentiation processes. Through bioinformatics analysis and luciferase reporter assays, homeobox protein Hox‐B7 (HOXB7) was identified as a potential novel downstream target of miR‐24 that contains a miR‐24 binding site in the 3′‐UTR of its mRNA. Overexpression of HOXB7 could partly halt the inhibitory effect of miR‐24 on osteogenesis, and downregulation of HOXB7 could also partly suppress the positive effect of miR‐24 on adipogenesis. Furthermore, immunoprecipitation experiments found that HOXB7 and β‐catenin formed a functional complex that acted as an essential modulator during osteogenesis and adipogenesis of ADMSCs. After transfecting ADMSCs with an MSNs‐PEI‐miR‐24 agomir or antagomir and loading the cells onto gelatin‐chitosan scaffolds, the compounds were assessed for their abilities to repair the critical‐sized calvarial defects in rats. Comprehensive evaluation, including micro‐CT, sequential fluorescent labeling, and immunohistochemistry analysis, revealed that silencing miR‐24 distinctly promoted in vivo bone remolding, whereas overexpression of miR‐24 significantly repressed bone formation. Taken together, our findings demonstrated opposite roles for the miR‐24/HOXB7/β‐catenin signaling pathway in the osteogenesis and adipogenesis of ADMSCs, which may provide a novel mechanism for determining the balance between these two biological processes.