Cartilage degeneration and excessive subchondral bone formation in spontaneous osteoarthritis involves altered TGF-β signaling

Weiwei Zhao, Ting Wang, Qiang Luo, Yan Chen, Victor Y L Leung, Chunyi Wen, Mohammed F. Shah, Haobo Pan, Kwongyuen Chiu, Xu Cao, William W. Lu

Research output: Contribution to journalArticle

Abstract

Transforming growth factor-β (TGF-β) has been demonstrated as a potential therapeutic target in osteoarthritis. However, beneficial effects of TGF-β supplement and inhibition have both been reported, suggesting characterization of the spatiotemporal distribution of TGF-β during the whole time course of osteoarthritis is important. To investigate the activity of TGF-β in osteoarthritis progression, we collected knee joints from Dunkin-Hartley (DH) guinea pigs at 3, 6, 9, and 12-month old (n=8), which develop spontaneous osteoarthritis in a manner extraordinarily similar to humans. Via histology and micro-computed tomography (CT) analysis, we found that the joints exhibited gradual cartilage degeneration, subchondral plate sclerosis, and elevated bone remodeling during aging. The degenerating cartilage showed a progressive switch of the expression of phosphorylated Smad2/3 to Smad1/5/8, suggesting dual roles of TGF-β/Smad signaling during chondrocyte terminal differentiation in osteoarthritis progression. In subchondral bone, we found that the locations and age-related changes of osterix+ osteoprogenitors were in parallel with active TGF-β, which implied the excessive osteogenesis may link to the activity of TGF-β. Our study, therefore, suggests an association of cartilage degeneration and excessive bone remodeling with altered TGF-β signaling in osteoarthritis progression of DH guinea pigs.

Original languageEnglish (US)
JournalJournal of Orthopaedic Research
DOIs
StateAccepted/In press - 2015

Fingerprint

Transforming Growth Factors
Osteogenesis
Osteoarthritis
Cartilage
Bone Remodeling
Guinea Pigs
Sclerosis
Chondrocytes
Knee Joint
Histology
Joints
Tomography
Bone and Bones

Keywords

  • Dunkin-Hartley guinea pig
  • Spontaneous osteoarthritis
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Cartilage degeneration and excessive subchondral bone formation in spontaneous osteoarthritis involves altered TGF-β signaling. / Zhao, Weiwei; Wang, Ting; Luo, Qiang; Chen, Yan; Leung, Victor Y L; Wen, Chunyi; Shah, Mohammed F.; Pan, Haobo; Chiu, Kwongyuen; Cao, Xu; Lu, William W.

In: Journal of Orthopaedic Research, 2015.

Research output: Contribution to journalArticle

Zhao, Weiwei ; Wang, Ting ; Luo, Qiang ; Chen, Yan ; Leung, Victor Y L ; Wen, Chunyi ; Shah, Mohammed F. ; Pan, Haobo ; Chiu, Kwongyuen ; Cao, Xu ; Lu, William W. / Cartilage degeneration and excessive subchondral bone formation in spontaneous osteoarthritis involves altered TGF-β signaling. In: Journal of Orthopaedic Research. 2015.
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