Cartilage degeneration and excessive subchondral bone formation in spontaneous osteoarthritis involves altered TGF-β signaling.
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.
Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Weiwei
W
Zhao
Centre for Human Tissues & Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shen Zhen, China.
Ting
T
Wang
Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Qiang
Q
Luo
Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Yan
Y
Chen
Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Victor Y L
VY
Leung
Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Chunyi
C
Wen
Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Mohammed F
MF
Shah
Centre for Human Tissues & Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shen Zhen, China.
Haobo
H
Pan
Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
KwongYuen
K
Chiu
Department of Orthopaedic Surgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Xu
X
Cao
Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
William W
WW
Lu
D000375:Aging / Q000473:pathology; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D016723:Bone Remodeling; D001842:Bone and Bones / Q000473:pathology*; D002358:Cartilage, Articular / Q000473:pathology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology*; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D051785:Smad Proteins; D016212:Transforming Growth Factor beta
Dunkin-Hartley guinea pig; spontaneous osteoarthritis; transforming growth factor-β