Aberrant Activation of TGF-β in Subchondral Bone at the Onset of Rheumatoid Arthritis Joint Destruction.

ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disease that often leads to joint destruction. A myriad of drugs targeting the immune abnormalities and downstream inflammatory cascades have been developed, but the joint destruction is not effectively halted. Here we report that aberrant activation of TGF-β in the subchondral bone marrow by immune response increases osteoprogenitors and uncoupled bone resorption and formation in RA mouse/rat models. Importantly, either systemic or local blockade of TGF-β activity in the subchondral bone attenuated articular cartilage degeneration in RA. Moreover, conditional deletion of TGF-β receptor II (Tgfbr2) in nestin-positive cells also effectively halted progression of RA joint destruction. Our data demonstrate that aberrant activation of TGF-β in the sub

SUBMITTER: Xu X 

PROVIDER: S-EPMC4809636 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature