FZD6 mediates the contributing role of miR-199a-5p in the adipogenesis of bone marrow mesenchymal stem cells derived from aplastic anemia.

Accumulating evidence indicates that enhanced adipogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) derived from aplastic anemia (AA) could contribute to the excessive fat accumulation in the bone marrow. However, the underlying molecular mechanism remains to be determined. Here in this study, we further characterized the contributing role of miR-199a-5p in adipogenesis of AA BM-MSCs through specific inhibition of miR-199a-5p expression. Subsequently, we performed a systematic screening of the downstream targets of miR-199a-5p through web tool prediction, profiling data analysis, and experimental validation, with FZD6 and CELSR1 identified as the most promising targets of miR-199a-5p in the adipogenesis of AA BM-MSCs. Finally, we mainly focused on FZD6, which presents prominently decreased expression in adipogenic differentiation and AA BM-MSC samples and negatively correlates with miR-199a-5p expression. Besides, FZD6 is demonstrated as a negative regulator of adipogenesis of BM-MSCs, and overexpression of FZD6 alleviates the facilitating role of miR-199a-5p in the adipogenic differentiation of BM-MSCs. Overall, our findings provide further mechanistic insights into miR-199a-5p-mediated enhanced adipogenesis of AA BM-MSCs, implicating miR-199a-5p and FZD6 as potential intervention targets for improving BM-MSC-mediated microenvironments.