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However, the role of MSCs in the development of abnormal angiogenesis in patients with ankylosing spondylitis (AS) remains unclear. In this study, we cultured human umbilical vein endothelial cells (HUVECs) with bone marrow-derived MSCs from patients with AS (ASMSCs) or healthy donors (HDMSCs) in vitro. Then, the cocultured HUVECs were assayed using a cell counting kit-8 (CCK-8) to evaluate the cell proliferation. A wound healing assay was performed to investigate cell migration, and a tube formation assay was conducted to determine the angiogenesis efficiency. ASMSCs exhibited increased angiogenesis, and increased expression of SMAD-specific E3 ubiquitin ligase 2 (Smurf2) in MSCs was the main cause of abnormal angiogenesis in patients with AS. Downregulation of Smurf2 in ASMSCs blocked angiogenesis, whereas overexpression of Smurf2 in HDMSCs promoted angiogenesis. The pro-angiogenic effect of Smurf2 was confirmed by the results of a Matrigel plug assay in vivo. By functioning as an E3 ubiquitin ligase in MSCs, Smurf2 regulated the levels of pentraxin 3 (PTX3), which has been shown to suppress angiogenesis through the PTX3-fibroblast growth factor 2 pathway. Moreover, Smurf2 transcription was regulated by activating transcription factor 4-induced endoplasmic reticulum stress. In conclusion, these results identify novel roles of Smurf2 in negatively regulating PTX3 stability and promoting angiogenesis in ASMSCs.<\/jats:p>","DOI":"10.1002\/stem.3332","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T05:29:01Z","timestamp":1637904541000},"page":"581-599","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["SMAD-specific E3 ubiquitin ligase 2 promotes angiogenesis by facilitating PTX3 degradation in MSCs from patients with ankylosing spondylitis"],"prefix":"10.1093","volume":"39","author":[{"given":"Mengjun","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaopeng","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rujia","family":"Mi","sequence":"additional","affiliation":[{"name":"Center for Biotherapy, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyu","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Sui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Biotherapy, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0638-0182","authenticated-orcid":false,"given":"Huiyong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China"},{"name":"Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of 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