Swiprosin-1 Negatively Regulates Osteoclast Differentiation and Bone Resorption via Akt/MAPK/NF-κB Pathway and αvβ3 Integrin-Dependent Signaling.

ABSTRACT: Swiprosin-1 (SWS1/EFhd2) is a calcium-binding adaptor protein involved in cytoskeletal regulation, but its physiological role in bone homeostasis remains largely undefined. To elucidate its function in osteoclast biology, we examined SWS1 expression and activity during osteoclastogenesis using primary murine bone marrow-derived macrophages, siRNA-mediated knockdown, and SWS1 knockout (KO) mice. SWS1 was predominantly localized to the nucleus in precursor cells and redistributed to the F-actin ring in mature osteoclasts. Receptor activator of nuclear factor-kappa B ligand stimulation significantly downregulated SWS1 mRNA expression. Loss of SWS1 enhanced osteoclast formation, F-actin ring integrity, and bone resorption, accompanied by elevated expression of osteoclastogenic markers. In vivo

SUBMITTER: Cheon YH 

PROVIDER: S-EPMC12429813 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature