Baicalein limits subchondral bone lesions via AMPKα/BECN1 activation in osteoarthritis osteoblast.

Abstract

Subchondral bone lesions play an important role in the pathogenesis of osteoarthritis (OA); however, there is currently no effective treatment. Baicalein, a flavonoid derived from Scutellaria, had been used as an antioxidant and anti-inflammatory agent. This study aimed to investigate the effect of baicalein on the development of OA in subchondral bone. We induced an in vivo medial meniscus (DMM) model of OA in 8-week-old wild-type and AMP-activated protein kinase α (AMPKα) knockout mice and used OA osteoblasts in vitro. Baicalein limited the expression of TGF-β1, COL1, and RUNX2 in OA osteoblasts in vitro and alleviated the OARSI score and reduced osteophyte size, osteophyte maturity, bone mineral density, and trabecular thickness in OA mice in vivo. Baicalein targeted residues Asp90 and Asn50 of AMPKα and activated AMPK phosphorylation. Inhibition of AMPKα phosphorylation attenuated the protective effects of baicalein on OA osteoblasts and subchondral bone. AMPKα reduced the expression of abnormal phenotypes by upregulating BECN1 expression. In addition, AMPKα co-activated BECN1. These results indicate that baicalein can alleviate subchondral bone lesions by increasing AMPKα/BECN1 signaling in OA, revealing baicalein as a potential therapeutic strategy for OA.