Arctigenin Modulates Adipogenic-Osteogenic Balance in the Bone Marrow Microenvironment of Ovariectomized Rats via the MEK1/PPARγ/Wnt/β-Catenin Pathway.

Autor: Li H; Department of Orthopedic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.; Department of Orthopedic Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China., Liao X; Department of Orthopedic Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China., Lan M; Department of Orthopedic Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China., He J; Department of Orthopedic Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China., Gao J; Department of Orthopedic Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China., Fan Z; Department of Orthopedic Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China., Huang J; Department of Orthopedic Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China., Wu X; Department of Orthopedic Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China., Chen J; Department of Orthopedic Surgery, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China., Sun G; Department of Orthopedic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Jazyk: angličtina
Zdroj: Chemical biology & drug design [Chem Biol Drug Des] 2024 Sep; Vol. 104 (3), pp. e14625.
DOI: 10.1111/cbdd.14625
Abstrakt: Arctigenin (Ar) is a promising therapeutic candidate for postmenopausal osteoporosis (PMOP). This study explores its mechanism by examining its effects on adipogenesis and osteogenesis in ovariectomized (OVX) rats. In vitro, Ar effectively suppressed the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) from OVX rats, reducing lipid droplet formation and downregulating proteins associated with lipid synthesis. In vivo, Ar treatment significantly reduced bone loss, inhibited adipocyte development, improved lipid metabolism, and promoted bone formation in OVX rats. Mechanistically, Ar inhibited the phosphorylation of Mitogen-Activated Protein Kinase 1 (MEK1), downregulated Peroxisome Proliferator-Activated Receptor gamma (PPARγ), promoted the accumulation of β-catenin in the nucleus, and prevented the direct binding of PPARγ to β-catenin in BMSCs. This regulation of the PPARγ/Wnt signaling axis underlies its dual role in inhibiting adipogenesis and promoting osteogenesis. Notably, co-treatment with rosiglitazone (RGZ) reversed the effects of Ar on adipogenesis and osteogenesis without affecting MEK1 inhibition. These findings offer valuable insights into arctigenin's potential as a therapeutic strategy for PMOP by modulating MEK1 signaling and regulating the PPARγ/Wnt axis.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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