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

Xin Xu, Liwei Zheng, Qin Bian, Liang Xie, Wenlong Liu, Gehua Zhen, Janet L. Crane, Xuedong Zhou, Xu Cao

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)2033-2043
Number of pages11
JournalJournal of Bone and Mineral Research
Volume30
Issue number11
DOIs
StatePublished - 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

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