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HMGA1 Aids the NFIX-mediated Osteogenesis of MSCs

Bone homeostasis depends largely on the number and function of osteoblasts; however, bone marrow mesenchymal stem cells (MSCs) give rise to both osteoblasts and adipocytes, and a competitive relationship exists between adipogenesis and osteogenesis. In a recent STEM CELLS article, researchers led by Baoli Wang (Tianjin Medical University, Tianjin, China) identify a novel nuclear factor I/X (NFIX)-high-mobility group AT-Hook 1 (HMGA1)-Wnt/β-catenin regulatory axis that governs the cell fate of MSCs by favoring osteoblast differentiation and blocking adipocyte formation. Wu et al. report that HMGA1, as a downstream target of NFIX, functions by transcriptionally regulating low-density lipoprotein receptor-related protein 5 (LRP5) expression and thereafter activating canonical Wnt signaling. Overall, this exciting new study suggests NFIX/HMGA1 as a novel therapeutic target for treating metabolic bone disorders such as osteoporosis.