ECEESPE2025 Poster Presentations MTEabolism, Nutrition and Obesity (125 abstracts)
Piezo1 activation suppresses bone marrow adipogenesis for healthy skeleton through inhibition of a mechanoinflammatory autocrine loop
Baile Wang 1 , Jie Liu 1 , Malika Arhatte 2 , Lai Yee Cheong 1 , Edyta Glogowska 2 , Xue Jiang 1 , Qin Wang 1 , Eric Honoré 2 & Aimin Xu 1
1State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Department of Medicine, The University of Hong Kong, Hong Kong, Hong Kong; 2Université Côte d’Azur, Centre National de la Recherche Scientifique, Institut national de la santé et de la recherche médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France
JOINT2061
With aging or upon osteoporosis, bone marrow adipogenesis is enhanced and inversely correlates with the loss of bone mass. Bone marrow adipocytes are derived from the multipotent bone marrow mesenchymal stem cells (BMMSCs), which can differentiate into either fat or bone. BMMSCs are mechano-sensitive cells, but how mechanical loading is implicated in the in vivo regulation of bone marrow adipogenesis and its impact on bone remodeling remains poorly understood. Here we identify the mechanosensitive cationic channel Piezo1 in BMMSCs as a key suppressor of bone marrow adipogenesis by preventing local inflammation, thereby enhancing osteoblast differentiation and bone formation. Mice with a specific Piezo1 invalidation in BMMSCs exhibit lower body weight, osteoporosis, and marrow adiposity, together with a resistance to the beneficial effects of exercise on bone health. Accordingly, Piezo1-deficient BMMSCs In vitro preferentially differentiate into adipocytes rather than osteoblasts. Mechanistically, Piezo1 invalidation enables c-Jun activation to increase Ccl2 production, while autocrine activation of CCR2 by Ccl2 induces the expression and secretion of lipocalin-2 (Lcn2) via NF-κB activation, thereby promoting BMMSCs adipogenesis. Conversely, pharmacological inhibition of Ccl2 signaling and shRNA-mediated knockdown or antibody-mediated blockage of Lcn2 inhibit adipogenesis but restore osteogenesis in Piezo1-deficient BMMSCs. Collectively, these findings demonstrate that Piezo1 activation in BMMSCs suppresses bone marrow adipogenesis to maintain skeleton strength by preventing the Ccl2-Lcn2 inflammatory autocrine loop, thus uncovering a previously unrecognized link between mechanotransduction, inflammation, and cell fate determination.
Acknowledgments: This work was supported by the Hong Kong Research Grants Council/Area of Excellence (AoE/M/707-18), the Hong Kong Research Grants Council/General Research Fund (17125317, 17120022), the Human Frontier Science Program (RGP0024/2017), and the Health and Medical Research Fund (07182836).
Volume 110
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2025 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more