TRIM27 Ubiquitinates and Degrades PPARγ to Promote Osteogenic Differentiation of BMSCs and Alleviate Osteoporosis.

OBJECTIVE

This study elucidates the role of TRIM27 in osteogenic differentiation and osteoporosis pathogenesis, focusing on its regulatory mechanism through PPARγ.

METHODS

TRIM27 expression was assessed during osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) via RT-qPCR and western blot. TRIM27 was knocked down (sh-TRIM27) or overexpressed (Lv-TRIM27) to evaluate its impact on alkaline phosphatase (ALP) activity, mineralization (Alizarin Red S staining), and osteogenic markers (COL1A1, OPN, and OCN). An ovariectomized (OVX) mouse osteoporosis model was established to analyze TRIM27 expression and bone microstructure (H&E staining). Co-immunoprecipitation (Co-IP) and cycloheximide chase assays identified TRIM27-PPARγ interactions and degradation dynamics. Rescue experiments combined sh-TRIM27 with PPARγ knockdown (sh-PPARγ) or the agonist rosiglitazone (ROZ).

RESULTS

TRIM27 expression increased 2.1-fold during BMSC osteogenic differentiation but decreased in OVX mice (p < 0.01 vs. sham). TRIM27 overexpression enhanced ALP activity, mineralization, and osteogenic markers (p < 0.05), while knockdown exerted opposite effects. TRIM27 directly bound PPARγ and promoted its ubiquitin-mediated degradation. PPARγ knockdown reversed sh-TRIM27-mediated inhibition of osteogenesis. In OVX mice, Lv-TRIM27 reduced bone loss by suppressing PPARγ, whereas ROZ abolished this protective effect.

CONCLUSION

TRIM27, as a key osteogenic promoter, ameliorates osteoporosis by targeting the degradation of PPARγ. Our research reveals the potential of TRIM27 in treating bone metabolism disorders and may become a potential target for the treatment of osteoporosis.