Extracellular microfibrils control osteoblast-supported osteoclastogenesis by restricting TGF{beta} stimulation of RANKL production.

ABSTRACT: Mutations in fibrillin-1 or fibrillin-2, the major structural components of extracellular microfibrils, cause pleiotropic manifestations in Marfan syndrome and congenital contractural arachnodactyly, respectively. We recently found that fibrillin-1 and fibrillin-2 control bone formation by regulating osteoblast differentiation through the differential modulation of endogenous TGFβ and bone morphogenetic protein signals. Here, we describe in vivo and ex vivo experiments that implicate the fibrillins as negative regulators of bone resorption. Adult Fbn2(-/-) mice display a greater than normal osteolytic response to locally implanted lipopolysaccharide-coated titanium particles. Although isolated cultures of Fbn2(-/-) preosteoclasts exhibited normal differentiation and activity, these feature

SUBMITTER: Nistala H 

PROVIDER: S-EPMC2962511 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature