Nr4a1 Enhances Wnt4 Transcription to Promote Osteogenic Differentiation of Mesenchymal Stem Cells and Alleviates Inflammation-Inhibited Bone Regeneration

The authors found that the expression of orphan nuclear receptor Nr4a1, an endogenous repressor of TGF-β1, was suppressed directly by TGF-β1-induced Smad3 and indirectly by Hdac4, respectively. Importantly, Nr4a1 overexpression promoted bone marrow MSC osteogenesis and reversed TGF-β1-mediated osteogenic inhibition and pro-fibrotic effects.