Resveratrol reverses osteogenic decline of bone marrow mesenchymal stem cells. - GreenMedInfo Summary
Resveratrol Reverses Osteogenic Decline of Bone Marrow Mesenchymal Stem Cells via Upregulation of YAP Expression in Inflammatory Environment.
Stem Cells Dev. 2021 Oct 1. Epub 2021 Oct 1. PMID: 34598655
Zihan Wang
Osteoporosis is an age-related bone disease, characterized by rapid bone loss, decreased bone mineral density (BMD), and consequent risk of fractures. The most prevalent form of clinically significant osteoporosis involves various inflammatory conditions, especially age-dependent osteoporosis and postmenopausal osteoporosis. Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, plays a critical role in the development of inflammatory, which also plays an important role in bone formation and bone loss during osteoporosis. In this report, we examined the effect of TNF-α on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and its modulation by resveratrol. We found that TNF-α can upregulate inflammatory cytokines, Il-6, Mmp-9, and Il-1β, and establish an inflammatory environment. High inflammatory cytokine expression significantly inhibited osteogenic differentiation of BMSCs by overactivating upstreamHippo kinases and decreasing the nuclear YAP signals. With resveratrol (Res) treatment, decreasing inflammatory cytokine expression normalized Hippo/YAP signaling and effectively rescued YAP-mediated osteogenesis. Thus, through these studies, we present a mechanism by which TNF-α can affect BMSCsosteogenesis through modulation of Hippo/YAP signaling.