We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis.
- Authors
Zhen, Gehua; Wen, Chunyi; Jia, Xiaofeng; Li, Yu; Crane, Janet L; Mears, Simon C; Askin, Frederic B; Frassica, Frank J; Chang, Weizhong; Yao, Jie; Carrino, John A; Cosgarea, Andrew; Artemov, Dmitri; Chen, Qianming; Zhao, Zhihe; Zhou, Xuedong; Riley, Lee; Sponseller, Paul; Wan, Mei; Lu, William Weijia
- Abstract
Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for the condition because of limited understanding of its pathogenesis. We show that transforming growth factor β1 (TGF-β1) is activated in subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) mouse model of osteoarthritis. TGF-β1 concentrations are also high in subchondral bone from humans with osteoarthritis. High concentrations of TGF-β1 induced formation of nestin-positive mesenchymal stem cell (MSC) clusters, leading to formation of marrow osteoid islets accompanied by high levels of angiogenesis. We found that transgenic expression of active TGF-β1 in osteoblastic cells induced osteoarthritis, whereas inhibition of TGF-β activity in subchondral bone attenuated the degeneration of articular cartilage. In particular, knockout of the TGF-β type II receptor (TβRII) in nestin-positive MSCs led to less development of osteoarthritis relative to wild-type mice after ACLT. Thus, high concentrations of active TGF-β1 in subchondral bone seem to initiate the pathological changes of osteoarthritis, and inhibition of this process could be a potential therapeutic approach to treating this disease.
- Subjects
TRANSFORMING growth factors-beta; CELLULAR signal transduction; MESENCHYMAL stem cells; OSTEOARTHRITIS; DISEASE prevalence; JOINT diseases; CRUCIATE ligament surgery
- Publication
Nature Medicine, 2013, Vol 19, Issue 6, p704
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm.3143