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Aberrant Activation of TGF‐β in Subchondral Bone at the Onset of Rheumatoid Arthritis Joint Destruction
Author(s) -
Xu Xin,
Zheng Liwei,
Bian Qin,
Xie Liang,
Liu Wenlong,
Zhen Gehua,
Crane Janet L,
Zhou Xuedong,
Cao Xu
Publication year - 2015
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.2550
Subject(s) - rheumatoid arthritis , medicine , transforming growth factor , arthritis , subchondral bone , pathology , osteoarthritis , articular cartilage , alternative medicine
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