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 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.
Original language | English (US) |
---|---|
Pages (from-to) | 2033-2043 |
Number of pages | 11 |
Journal | Journal of Bone and Mineral Research |
Volume | 30 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2015 |
Keywords
- CARTILAGE DEGENERATION
- MESENCHYMAL STEM CELLS
- RHEUMATOID ARTHRITIS
- SUBCHONDRAL BONE
- TGF-β
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Orthopedics and Sports Medicine