Mechanical Unloading Promotes Osteoclastic Differentiation and Bone Resorption by Modulating the MSC Secretome to Favor Inflammation.

ABSTRACT: Aging, space flight, and prolonged bed rest have all been linked to bone loss, and no effective treatments are clinically available at present. Here, with the rodent hindlimb unloading (HU) model, we report that the bone marrow (BM) microenvironment was significantly altered, with an increased number of myeloid cells and elevated inflammatory cytokines. In such inflammatory BM, the osteoclast-mediated bone resorption was greatly enhanced, leading to a shifted bone remodeling balance that ultimately ends up with disuse-induced osteoporosis. Using Piezo1 conditional knockout (KO) mice (Piezo1^fl/fl;LepRCre), we proved that lack of mechanical stimuli on LepR⁺ mesenchymal stem cells (MSCs) is the main reason for the pathological BM inflammation. Mechanically, the secretome

SUBMITTER: Wang W 

PROVIDER: S-EPMC10953070 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature