Inhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis.

TitleInhibition of TGF-β signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis.
Publication TypeJournal Article
Year of Publication2013
AuthorsZhen G, Wen C, Jia X, Li Y, Crane JL, Mears SC, Askin FB, Frassica FJ, Chang W, Yao J, Carrino JA, Cosgarea A, Artemov D, Chen Q, Zhao Z, Zhou X, Riley L, Sponseller P, Wan M, Lu WW, Cao X
JournalNature medicine
Volume19
Issue6
Pagination704-12
Date Published2013 Jun
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.

DOI10.1155/2013/638582
Alternate JournalNat. Med.