{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:02:13Z","timestamp":1776769333411,"version":"3.51.2"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"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":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"vor","delay-in-days":463,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Clinical and Translational Research Funding Program, Washington University Institute of Clinical and Translational Sciences (ICTS), NIH Clinical Translational Sciences Award"},{"name":"Foundation for Women's Wellness Fellowship Award"},{"name":"Initiative for Maximizing Student Diversity (IMSD)-Exposure to Research for Science Students (EXPRESS) program"},{"name":"Kansas City Consortium on Musculoskeletal Diseases (KCMD) Collaborative Research for Neuromuscular\/Musculoskeletal Disorders pilot grant"},{"name":"University of Missouri College of Agriculture, Food and Natural Resources"},{"name":"University of Missouri School of Medicine Child Health Research Institute"},{"name":"Wayne L. Ryan Fellowship through The Ryan Foundation"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osteogenesis imperfecta (OI) is a collagen-related bone disorder characterized by fragile osteopenic bone and muscle weakness. We have previously shown that the soluble activin receptor type IIB decoy (sActRIIB) molecule increases muscle mass and improves bone strength in the mild to moderate G610C mouse model of OI. The sActRIIB molecule binds multiple transforming growth factor-\u03b2 (TGF-\u03b2) ligands, including myostatin and activin A. Here, we investigate the musculoskeletal effects of inhibiting activin A alone, myostatin alone, or both myostatin and activin A in wild-type (Wt) and heterozygous G610C (+\/G610C) mice using specific monoclonal antibodies. Male and female Wt and +\/G610C mice were treated twice weekly with intraperitoneal injections of monoclonal control antibody (Ctrl-Ab, Regn1945), anti-activin A antibody (ActA-Ab, Regn2476), anti-myostatin antibody (Mstn-Ab, Regn647), or both ActA-Ab and Mstn-Ab (Combo, Regn2476, and Regn647) from 5 to 16\u2009weeks of age. Prior to euthanasia, whole body composition, metabolism and muscle force generation assessments were performed. Post euthanasia, hindlimb muscles were evaluated for mass, and femurs were evaluated for changes in microarchitecture and biomechanical strength using micro\u2013computed tomography (\u03bcCT) and three-point bend analyses. ActA-Ab treatment minimally impacted the +\/G610C musculoskeleton, and was detrimental to bone strength in male +\/G610C mice. Mstn-Ab treatment, as previously reported, resulted in substantial increases in hindlimb muscle weights and overall body weights in Wt and male +\/G610C mice, but had minimal skeletal impact in +\/G610C mice. Conversely, the Combo treatment outperformed ActA-Ab alone or Mstn-Ab alone, consistently increasing hindlimb muscle and body weights regardless of sex or genotype and improving bone microarchitecture and strength in both male and female +\/G610C and Wt mice. Combinatorial inhibition of activin A and myostatin more potently increased muscle mass and bone microarchitecture and strength than either antibody alone, recapturing most of the observed benefits of sActRIIB treatment in +\/G610C mice. \u00a9 2022 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4529","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T06:49:38Z","timestamp":1645598978000},"page":"938-953","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Combinatorial Inhibition of Myostatin and Activin A Improves Femoral Bone Properties in the G610C Mouse Model of Osteogenesis Imperfecta"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0750-2129","authenticated-orcid":false,"given":"Catherine L.","family":"Omosule","sequence":"first","affiliation":[{"name":"Department of Biochemistry University of 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngjae","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Missouri Columbia MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashique","family":"Rafique","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Tarrytown NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela","family":"Krueger","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Tarrytown NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Kleiner","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Tarrytown NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7761-3783","authenticated-orcid":false,"given":"Charlotte L.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Child Health University of Missouri Columbia MO USA"},{"name":"Department of Biochemistry University of Missouri Columbia MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"2024012713595665900_jbmr4529-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 Primer"},{"issue":"10028","key":"2024012713595665900_jbmr4529-bib-0002","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/S0140-6736(15)00728-X","article-title":"Osteogenesis imperfecta","volume":"387","author":"Forlino","year":"2016","journal-title":"Lancet"},{"issue":"9","key":"2024012713595665900_jbmr4529-bib-0003","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nrendo.2011.81","article-title":"New perspectives on osteogenesis 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