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Symptoms of CED include bone pain, fractures, and dysplasia. Currently, effective therapies for bone fracture and dysplasia in CED are urgently needed. We have demonstrated that TGF\u2010\u03b21 is a coupling factor for bone remodeling and is aberrantly activated in CED. Daily injection of TGF\u2010\u03b2 type 1 receptor inhibitor (T\u03b2R1I) attenuated CED symptoms, but this systemic administration caused serious side effects. In this study, we created a conjugate linking T\u03b2R1I and alendronate, which delivered T\u03b2R1I specifically to bone. After weekly injection of the conjugate for 8 weeks, normal bone morphology and remodeling in CED mice was maintained with a minimum effective dose 700 times lower than T\u03b2R1I injection. Additionally, we found that the conjugate restored normal bone turnover by reducing the number of osteoblasts and osteoclasts, maintained a regular osteogenic microenvironment by regulating the formation of CD31 and Endomucin double\u2010positive vessels, and preserved ordinary bone formation via inhibition of the migration of leptin\u2010receptor\u2010positive cells. Thus, targeting delivery of T\u03b2R1I to bone is a promising therapy for CED and other uncoupled bone remodeling disorders.<\/jats:p>","DOI":"10.1111\/nyas.13941","type":"journal-article","created":{"date-parts":[[2018,8,9]],"date-time":"2018-08-09T11:04:18Z","timestamp":1533812658000},"page":"29-40","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Bone\u2010targeted delivery of TGF\u2010\u03b2 type 1 receptor inhibitor rescues uncoupled bone remodeling in Camurati\u2013Engelmann disease"],"prefix":"10.1111","volume":"1433","author":[{"given":"Yunhao","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Johns Hopkins University School of Medicine  Baltimore Maryland"},{"name":"Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibing","family":"Tang","sequence":"additional","affiliation":[{"name":"Gladstone Institute of Cardiovascular Disease Department of Pharmaceutical Chemistry University of California, San Francisco  San Francisco California"},{"name":"Drug Discovery Pipeline Guangzhou Institutes of Biomedicine and Health  Science City Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gehua","family":"Zhen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Johns Hopkins University School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Ding","sequence":"additional","affiliation":[{"name":"Othro Therapeutics Co., Ltd.  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