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.

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