Single cell analysis reveals inhibition of angiogenesis attenuates the progression of heterotopic ossification in Mkx^(−/−)mice

作     者：Junxin Lin Yuwei Yang Wenyan Zhou Chao Dai Xiao Chen Yuanhao Xie Shan Han Huanhuan Liu Yejun Hu Chenqi Tang Varitsara Bunpetch Dandan Zhang Yishan Chen Xiaohui Zou Di Chen Wanlu Liu Hongwei Ouyang Junxin Lin;Yuwei Yang;Wenyan Zhou;Chao Dai;Xiao Chen;Yuanhao Xie;Shan Han;Huanhuan Liu;Yejun Hu;Chenqi Tang;Varitsara Bunpetch;Dan Zhang;Yishan Chen;Xiaohui Zou;Di Chen;Wanlu Liu;Hongwei Ouyang

作者机构：Dr.Li Dak Sum&Yip Yio Chin Center for Stem Cells and Regenerative Medicineand Department of Orthopedic Surgery of the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Department of Sports MedicineZhejiang University School of MedicineHangzhouChina Zhejiang University-University of Edinburgh InstituteZhejiang University School of Medicineand Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang ProvinceHangzhouChina China Orthopedic Regenerative Medicine Group(CORMed)HangzhouChina Department of PathologyZhejiang University School of MedicineHangzhouChina Clinical Research CenterThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Center for Reproductive MedicineThe Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina 

出 版 物：《Bone Research》 (骨研究（英文版）)

年 卷 期：2022年第10卷第4期

页      面：715-725页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：supported by the National Key R&D Program of China(2017YFA0104900) the National Natural Science Foundation of China(31830029,81501937 and 81522029) the Fundamental Research Funds for the Central Universities(K20200099) 

主　　题：angiogenesis ossification analysis 

摘      要：Tendon heterotopic ossification(HO)is characterized by bone formation inside tendon tissue,which severely debilitates people in their daily *** therapies fail to promote functional tissue repair largely due to our limited understanding of HO ***,we investigate the pathological mechanism and propose a potential treatment method for *** assays showed that the Mohawk(MKX)expression level was decreased in human tendon HO tissue,coinciding with spontaneous HO and the upregulated expression of osteochondrogenic and angiogenic genes in the tendons of Mkx^(−/−)***-cell RNA sequencing analyses of wild-type and Mkx^(−/−)tendons identified three cell types and revealed the excessive activation of osteochondrogenic genes during the tenogenesis of Mkx^(−/−)tendon ***-cell analysis revealed that the gene expression program of angiogenesis,which is strongly associated with bone formation,was activated in all cell types during ***,inhibition of angiogenesis by the small-molecule inhibitor BIBF1120 attenuated bone formation and angiogenesis in the Achilles tendons of both Mkx mutant mice and a rat traumatic model of *** findings provide new insights into the cellular mechanisms of tendon HO and highlight the inhibition of angiogenesis with BIBF1120 as a potential treatment strategy for HO.