CASIA OpenIR  > 中国科学院分子影像重点实验室
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
Source PublicationJOURNAL OF CLINICAL INVESTIGATION
2018-02-01
Volume128Issue:2Pages:846-860
SubtypeArticle
AbstractEnthesopathy 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 HeadingsScience & Technology ; Life Sciences & Biomedicine
DOI10.1172/JCI96186
WOS KeywordGROWTH-FACTOR-BETA ; MESENCHYMAL STEM-CELLS ; HUMAN INTERVERTEBRAL DISC ; ACHILLES-TENDON ; ARTICULAR-CARTILAGE ; ANKYLOSING-SPONDYLITIS ; RHEUMATOID-ARTHRITIS ; SUBCHONDRAL BONE ; X COLLAGEN ; MARROW
Indexed BySCI
Language英语
Funding OrganizationNIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases(AR071432 ; AR063943)
WOS Research AreaResearch & Experimental Medicine
WOS SubjectMedicine, Research & Experimental
WOS IDWOS:000424659500028
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/21958
Collection中国科学院分子影像重点实验室
Affiliation1.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
Recommended Citation
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.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Wang, Xiao]'s Articles
[Xie, Liang]'s Articles
[Crane, Janet]'s Articles
Baidu academic
Similar articles in Baidu academic
[Wang, Xiao]'s Articles
[Xie, Liang]'s Articles
[Crane, Janet]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Wang, Xiao]'s Articles
[Xie, Liang]'s Articles
[Crane, Janet]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.