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Mutation of COL1A1\/COL1A2 genes encoding the type I collagen are most responsible for the clinical patients. Allogenic mesenchymal stem cells (MSCs) provide the potential to treat OI through differentiation into osteoblasts. Autologous defective MSCs have not been utilized in OI treatment mainly because of their impaired osteogenesis, but the latent mechanism has not been well understood. Here, the relative signaling abnormality of adipose-derived mesenchymal stem cells (ADSCs) isolated from OI type I mice (Col1a1+\/\u2212365 mice) was explored. Autologous ADSCs transfected by retrovirus carrying human COL1A1 gene was first utilized in OI therapy. The results showed that decreased activity of Yes-associated protein (YAP) due to hyperactive upstream Hippo kinases greatly contributed to the weakened bone-forming capacity of defective ADSCs. Recovered collagen synthesis of autologous ADSCs by COL1A1 gene modification normalized Hippo\/YAP signaling and effectively rescued YAP-mediated osteogenesis. And the COL1A1 gene engineered autologous ADSCs efficaciously improved the microstructure, enhanced the mechanical properties and promoted bone formation of Col1a1+\/\u2212365 mice after femoral bone marrow cavity delivery and might serve as an alternative source of stem cells in OI treatment. \u00a9 2021 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4326","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T21:52:01Z","timestamp":1620251521000},"page":"1521-1534","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Modification of COL1A1 in Autologous Adipose Tissue-Derived Progenitor Cells Rescues the Bone Phenotype in a Mouse Model of Osteogenesis Imperfecta"],"prefix":"10.1093","volume":"36","author":[{"given":"Yi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Genetics School of Basic Medical Sciences, Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8193-7054","authenticated-orcid":false,"given":"Zihan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Genetics School of Basic Medical Sciences, Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyan","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Genetics School of Basic Medical Sciences, Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Genetics School of Basic Medical Sciences, Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqing","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Genetics School of Basic Medical Sciences, Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaci","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Genetics School of Basic Medical Sciences, Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyi","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Genetics School of Basic Medical Sciences, Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Genetics School of Basic Medical Sciences, Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Genetics School of Basic Medical Sciences, Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9608-0820","authenticated-orcid":false,"given":"Guang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Genetics School of Basic Medical Sciences, Tianjin Medical University Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"2024012713455840700_jbmr4326-bib-0001","doi-asserted-by":"crossref","first-page":"17052","DOI":"10.1038\/nrdp.2017.52","article-title":"Osteogenesis imperfecta","volume":"3","author":"Marini","year":"2017","journal-title":"Nat Rev Dis 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