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- Title
Aberrant Activation of TGF-β in Subchondral Bone at the Onset of Rheumatoid Arthritis Joint Destruction.
- Authors
Xu, Xin; Zheng, Liwei; Bian, Qin; Xie, Liang; Liu, Wenlong; Zhen, Gehua; Crane, Janet L; Zhou, Xuedong; Cao, Xu
- Abstract
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. © 2015 American Society for Bone and Mineral Research
- Subjects
RHEUMATOID arthritis; TRANSFORMING growth factors-beta; CARTILAGE diseases; MESENCHYMAL stem cells; BONE resorption; LABORATORY rats
- Publication
Journal of Bone & Mineral Research, 2015, Vol 30, Issue 11, p2033
- ISSN
0884-0431
- Publication type
Article
- DOI
10.1002/jbmr.2550