The Src family kinase, Lyn, suppresses osteoclastogenesis in vitro and in vivo.

ABSTRACT: c-Src kinase is a rate-limiting activator of osteoclast (OC) function and Src inhibitors are therefore candidate antiosteoporosis drugs. By affecting alphavbeta3 and macrophage-colony stimulating factor (M-CSF)-induced signaling, c-Src is central to osteoclast activity, but not differentiation. We find Lyn, another member of Src family kinases (SFK) is, in contrast, a negative regulator of osteoclastic bone resorption. The absence of Lyn enhances receptor activator of NF-kappaB ligand (RANKL)-mediated differentiation of osteoclast precursors without affecting proliferation and survival, while its overexpression decreases osteoclast formation. In further contrast to c-Src, Lyn deficiency does not impact the activity of the mature cell. Reflecting increased osteoclast development in vitro, L

SUBMITTER: Kim HJ 

PROVIDER: S-EPMC2650155 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature