Inhibition of TGF-[beta] signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis

	Inhibition of TGF-[beta] signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis
	Zhen, Gehua; Wen, Chunyi; Jia, Xiaofeng; Li, Yu; Crane, Janet L.; Mears, Simon C.; Askin, Frederic B.; Frassica, Frank J.; Chang, Weizhong; Yao, Jie
刊名	NATURE MEDICINE
	2013
英文摘要	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 beta 1 (TGF-beta 1) is activated in subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) mouse model of osteoarthritis. TGF-beta 1 concentrations are also high in subchondral bone from humans withosteoarthritis. High concentrations of TGF-beta 1 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-beta 1 in osteoblastic cells inducedosteoarthritis, whereas inhibition of TGF-beta activity in subchondral bone attenuated the degeneration of articular cartilage. In particular, knockout of the TGF-beta type II receptor (TbRII) in nestin-positive MSCs led to less development of osteoarthritis relative to wild-type mice after ACLT. Thus, high concentrations ofactive TGF-beta 1 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.
收录类别	SCI
原文出处	http://www.nature.com/nm/journal/v19/n6/full/nm.3143.html
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/5196]
专题	深圳先进技术研究院_医药所
作者单位	NATURE MEDICINE
推荐引用方式 GB/T 7714	Zhen, Gehua,Wen, Chunyi,Jia, Xiaofeng,et al. Inhibition of TGF-[beta] signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis[J]. NATURE MEDICINE,2013.
APA	Zhen, Gehua.,Wen, Chunyi.,Jia, Xiaofeng.,Li, Yu.,Crane, Janet L..,...&Cao, Xu.(2013).Inhibition of TGF-[beta] signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis.NATURE MEDICINE.
MLA	Zhen, Gehua,et al."Inhibition of TGF-[beta] signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis".NATURE MEDICINE (2013).