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Patients with clEDS2 exhibit hallmark features such as loose connective tissues, osteoporosis, and scoliosis. Despite its clinical significance, the molecular mechanisms underlying\n                    <jats:italic>AEBP1<\/jats:italic>\n                    mutations in skeletal development remain poorly understood, and effective therapeutic strategies are currently unavailable. Here, using\n                    <jats:italic>OsxCre<\/jats:italic>\n                    conditional KO mice, we show that\n                    <jats:italic>Aebp1<\/jats:italic>\n                    deletion in osteoprogenitors reduces body size and bone mass, recapitulating key skeletal features reported in clEDS2. In primary osteoblasts, both genetic deletion and siRNA-mediated knockdown of\n                    <jats:italic>Aebp1<\/jats:italic>\n                    impair osteoblast differentiation. Mechanistically,\n                    <jats:italic>Aebp1<\/jats:italic>\n                    loss attenuates Wnt\/\u03b2-catenin signaling in bone. Restoration of Wnt\/\u03b2-catenin signaling by injecting BIO, a small molecule inhibitor of GSK3, substantially rescued bone mass reduction in\n                    <jats:italic>Aebp1<\/jats:italic>\n                    -KO mice. These findings support a model in which\n                    <jats:italic>Aebp1<\/jats:italic>\n                    sustains baseline Wnt\/\u03b2-catenin tone in osteoblast-lineage cells and suggest that Wnt-targeted approaches may help mitigate clEDS2-related skeletal defects.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.191606","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T17:00:16Z","timestamp":1763053216000},"source":"Crossref","is-referenced-by-count":1,"title":["Aebp1 loss in osteoprogenitors leads to skeletal defects resembling Ehlers-Danlos Syndrome by diminishing Wnt\/\u03b2-catenin signaling"],"prefix":"10.1172","volume":"11","author":[{"given":"Shuhao","family":"Feng","sequence":"first","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihang","family":"Feng","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China."},{"name":"Department of Sports Medicine, Wuhan Fourth Hospital, Wuhan, Hubei Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghao","family":"Deng","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China."},{"name":"Department of Orthopedics, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People\u2019s Hospital), Dongguan, Guangdong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Wei","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China."},{"name":"Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Lian","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangchen","family":"Jin","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jin","sequence":"additional","affiliation":[{"name":"Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongmin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Joint Surgery Department, the First Affiliated Hospital of Guangzhou Medical 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