Institutional Repository of Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, Beijing 100190, Peoples R China
Aberrant TGF-beta activation in bone tendon insertion induces enthesopathy-like disease | |
Wang, Xiao1; Xie, Liang1,2; Crane, Janet1; Zhen, Gehua1; Li, Fengfeng1; Yang, Ping1,3; Gao, Manman1,4; Deng, Ruoxian1; Wang, Yiguo1; Jia, Xiaohua1,5; Fan, Cunyi6; Wan, Mei1; Cao, Xu1 | |
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 |
七大方向——子方向分类 | 医学影像处理与分析 |
国重实验室规划方向分类 | 其他 |
是否有论文关联数据集需要存交 | 否 |
引用统计 | |
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. |
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