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Cartilage degeneration and excessive subchondral bone formation in spontaneous osteoarthritis involves altered TGF‐β signaling
Author(s) -
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.
Publication year - 2016
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.23079
Subject(s) - osteoarthritis , cartilage , transforming growth factor , medicine , smad , chondrocyte , subchondral bone , degeneration (medical) , bone remodeling , pathology , anatomy , articular cartilage , alternative medicine
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. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:763–770, 2016.