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)
Pages (from-to)763-770
Number of pages8
JournalJournal of Orthopaedic Research
Volume34
Issue number5
DOIs
StatePublished - May 1 2016

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Keywords

  • Dunkin-Hartley Guinea pig
  • spontaneous osteoarthritis
  • transforming growth factor-β

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Zhao, W., Wang, T., Luo, Q., Chen, Y., Leung, V. Y. L., Wen, C., Shah, M. F., Pan, H., Chiu, K., Cao, X., & Lu, W. W. (2016). Cartilage degeneration and excessive subchondral bone formation in spontaneous osteoarthritis involves altered TGF-β signaling. Journal of Orthopaedic Research, 34(5), 763-770. https://doi.org/10.1002/jor.23079