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

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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Zhen 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

doi

10.1038/nm.3143

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

704-12

issue

6

eissn

1078-8956

issn

1546-170X

pii

nm.3143

journal_volume

19

pub_type

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