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 subchondral bone is involved at the onset of RA joint cartilage degeneration. Thus, modulation of subchondral bone TGF-β activity could be a potential therapy for RA joint destruction.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809636PMC
http://dx.doi.org/10.1002/jbmr.2550DOI Listing

Publication Analysis

Top Keywords

subchondral bone
20
joint destruction
20
aberrant activation
12
activation tgf-β
12
tgf-β subchondral
12
rheumatoid arthritis
8
effectively halted
8
tgf-β activity
8
cartilage degeneration
8
tgf-β
6

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!