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 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 1 2015

Fingerprint

Rheumatoid Arthritis
Joints
Bone and Bones
Nestin
Articular Cartilage
Drug Delivery Systems
Bone Resorption
Osteogenesis
Autoimmune Diseases
Cartilage
Bone Marrow
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Aberrant Activation of TGF-β in Subchondral Bone at the Onset of Rheumatoid Arthritis Joint Destruction. / Xu, Xin; Zheng, Liwei; Bian, Qin; Xie, Liang; Liu, Wenlong; Zhen, Gehua; Crane, Janet; Zhou, Xuedong; Cao, Xu.

In: Journal of Bone and Mineral Research, Vol. 30, No. 11, 01.11.2015, p. 2033-2043.

Research output: Contribution to journalArticle

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AU - Liu, Wenlong

AU - Zhen, Gehua

AU - Crane, Janet

AU - Zhou, Xuedong

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