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J Bone Miner Res. 2015 Nov;30(11):2033-43. doi: 10.1002/jbmr.2550. Epub 2015 Jun 8.

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

Xu X1,2, Zheng L1,2, Bian Q2,3, Xie L1,2, Liu W2,4, Zhen G2, Crane JL2,5, Zhou X1, Cao X2.

Author information

1
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, PR China.
2
Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3
Institute of Spine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China.
4
Department of Orthopaedics and Traumatology, Faculty of Medicine, The University of Hong Kong, Hong Kong, PR China.
5
Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA.

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.

KEYWORDS:

CARTILAGE DEGENERATION; MESENCHYMAL STEM CELLS; RHEUMATOID ARTHRITIS; SUBCHONDRAL BONE; TGF-β

PMID:
25967237
PMCID:
PMC4809636
DOI:
10.1002/jbmr.2550
[Indexed for MEDLINE]
Free PMC Article

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