{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:58:15Z","timestamp":1790513895143,"version":"4.1.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2018,5,29]],"date-time":"2018-05-29T00:00:00Z","timestamp":1527552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T00:00:00Z","timestamp":1529625600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>\u2003<\/jats:title><jats:p>Osteogenesis imperfecta (OI) is a heritable connective tissue disorder primarily due to mutations in the type I collagen genes (COL1A1 and COL1A2), leading to compromised biomechanical integrity in type I collagen-containing tissues such as bone. Bone is inherently mechanosensitive and thus responds and adapts to external stimuli, such as muscle mass and contractile strength, to alter its mass and shape. Myostatin, a member of the TGF-\u03b2 superfamily, signals through activin receptor type IIB to negatively regulate muscle fiber growth. Because of the positive impact of myostatin deficiency on bone mass, we utilized a soluble activin receptor type IIB-mFc (sActRIIB-mFc) fusion protein in two molecularly distinct OI mouse models (G610C and oim) and evaluated their bone properties. Wild-type (WT), +\/G610C, and oim\/oim mice were treated from 2 to 4 months of age with either vehicle (Tris-buffered saline) or sActRIIB-mFc (10\u2009mg\/kg). Femurs of sActRIIB-mFc-treated mice exhibited increased trabecular bone volume regardless of genotype, whereas the cortical bone microarchitecture and biomechanical strength were only improved in WT and +\/G610C mice. Dynamic histomorphometric analyses suggest the improved cortical bone geometry and biomechanical integrity reflect an anabolic effect due to increased mineral apposition and bone formation rates, whereas static histomorphometric analyses supported sActRIIB-mFc treatment also having an anti-catabolic impact with decreased osteoclast number per bone surface on trabecular bone regardless of sex and genotype. Together, our data suggest that sActRIIB-mFc may provide a new therapeutic direction to improve both bone and muscle properties in OI. \u00a9 2018 American Society for Bone and Mineral Research.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbmr.3473","type":"journal-article","created":{"date-parts":[[2018,5,29]],"date-time":"2018-05-29T20:49:44Z","timestamp":1527626984000},"page":"1760-1772","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Skeletal Response to Soluble Activin Receptor Type IIB in Mouse Models of Osteogenesis Imperfecta"],"prefix":"10.1093","volume":"33","author":[{"given":"Youngjae","family":"Jeong","sequence":"first","affiliation":[{"name":"Department of BiochemistryUniversity of MissouriColumbiaMOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salah A","family":"Daghlas","sequence":"additional","affiliation":[{"name":"Department of BiochemistryUniversity of 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CityMOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine L","family":"Omosule","sequence":"additional","affiliation":[{"name":"Department of BiochemistryUniversity of MissouriColumbiaMOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Scott","family":"Pearsall","sequence":"additional","affiliation":[{"name":"Acceleron PharmaInc.CambridgeMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L","family":"Dallas","sequence":"additional","affiliation":[{"name":"Department of Oral and Craniofacial SciencesSchool of DentistryUniversity of Missouri-Kansas CityKansas CityMOUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte L","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Child HealthUniversity of MissouriColumbiaMOUSA"},{"name":"Department of BiochemistryUniversity of 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