Aberrant TGF-beta activation in bone tendon insertion induces enthesopathy-like disease

doi:10.1172/JCI96186

	Aberrant TGF-beta activation in bone tendon insertion induces enthesopathy-like disease
	Wang, Xiao1 ; Xie, Liang 1,2; Crane, Janet 1; Zhen, Gehua 1; Li, Fengfeng 1; Yang, Ping 1,3; Gao, Manman 1,4; Deng, Ruoxian 1; Wang, Yiguo 1; Jia, Xiaohua1,5 ; Fan, Cunyi 6; Wan, Mei 1; Cao, Xu 1
发表期刊	JOURNAL OF CLINICAL INVESTIGATION
	2018-02-01
卷号	128 期号:2 页码:846-860
文章类型	Article
摘要	Enthesopathy is a disorder of bone, tendon, or ligament insertion. It represents one-fourth of all tendon-ligament diseases and is one of the most difficult tendon-ligament disorders to treat. Despite its high prevalence, the exact pathogenesis of this condition remains unknown. Here, we show that TGF-beta was activated in both a semi-Achilles tendon transection (SMTS) mouse model and in a dorsiflexion immobilization (DI) mouse model of enthesopathy. High concentrations of active TGF-beta recruited mesenchymal stromal stem cells (MSCs) and led to excessive vessel formation, bone deterioration, and fibrocartilage calcification. Transgenic expression of active TGF-beta 1 in bone also induced enthesopathy with a phenotype similar to that observed in SMTS and DI mice. Systemic inhibition of TGF-beta activity by injection of 1D11, a TGF-beta-neutralizing antibody, but not a vehicle antibody, attenuated the excessive vessel formation and restored uncoupled bone remodeling in SMTS mice. 1D11-treated SMTS fibrocartilage had increased proteoglycan and decreased collagen X and matrix metalloproteinase 13 expression relative to control antibody treatment. Notably, inducible knockout of the TGF-beta type II receptor in mouse MSCs preserved the bone microarchitecture and fibrocartilage composition after SMTS relative to the WT littermate controls. Thus, elevated levels of active TGF-beta in the enthesis bone marrow induce the initial pathological changes of enthesopathy, indicating that TGF-beta inhibition could be a potential therapeutic strategy.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
DOI	10.1172/JCI96186
关键词[WOS]	GROWTH-FACTOR-BETA ; MESENCHYMAL STEM-CELLS ; HUMAN INTERVERTEBRAL DISC ; ACHILLES-TENDON ; ARTICULAR-CARTILAGE ; ANKYLOSING-SPONDYLITIS ; RHEUMATOID-ARTHRITIS ; SUBCHONDRAL BONE ; X COLLAGEN ; MARROW
收录类别	SCI
语种	英语
项目资助者	NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases(AR071432 ; AR063943)
WOS研究方向	Research & Experimental Medicine
WOS类目	Medicine, Research & Experimental
WOS记录号	WOS:000424659500028
引用统计	被引频次：32[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.ia.ac.cn/handle/173211/21958
专题	中国科学院分子影像重点实验室
作者单位	1.Johns Hopkins Univ, Sch Med, Dept Orthoped Surg, Baltimore, MD USA 2.Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu, Sichuan, Peoples R China 3.Shihezi Univ, Sch Med, Affiliated Hosp 1, Dept Obstet & Gynecol, Shihezi, Xinjiang, Peoples R China 4.Sun Yat Sen Univ, Affiliated Hosp 1, Orthoped Res Inst, Dept Spinal Surg, Guangdong, Peoples R China 5.Chinese Acad Sci, Inst Automat, Key Lab Mol Imaging, Beijing, Peoples R China 6.Shanghai Sixth Peoples Hosp, Dept Orthoped Surg, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Wang, Xiao,Xie, Liang,Crane, Janet,et al. Aberrant TGF-beta activation in bone tendon insertion induces enthesopathy-like disease[J]. JOURNAL OF CLINICAL INVESTIGATION,2018,128(2):846-860.
APA	Wang, Xiao.,Xie, Liang.,Crane, Janet.,Zhen, Gehua.,Li, Fengfeng.,...&Cao, Xu.(2018).Aberrant TGF-beta activation in bone tendon insertion induces enthesopathy-like disease.JOURNAL OF CLINICAL INVESTIGATION,128(2),846-860.
MLA	Wang, Xiao,et al."Aberrant TGF-beta activation in bone tendon insertion induces enthesopathy-like disease".JOURNAL OF CLINICAL INVESTIGATION 128.2(2018):846-860.