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Observations of cellular and transcriptional responses to SclAb in OI have been limited to mouse models of the disorder, leaving a paucity of data on the human OI osteoblastic cellular response to the treatment. Here, we explore factors associated with response to SclAb therapy in vitro and in a novel xenograft model using OI bone tissue derived from pediatric patients. Bone isolates (approximately 2\u2009mm\n                    <jats:sup>3<\/jats:sup>\n                    ) from OI patients (OI type III, type III\/IV, and type IV,\n                    <jats:italic>n<\/jats:italic>\n                    =\u20097; non\u2010OI control,\n                    <jats:italic>n<\/jats:italic>\n                    =\u20095) were collected to media, randomly assigned to an untreated (UN), low\u2010dose SclAb (TRL, 2.5\u2009\u03bcg\/mL), or high\u2010dose SclAb (TRH, 25\u2009\u03bcg\/mL) group, and maintained in vitro at 37\u00b0C. Treatment occurred on days 2 and 4 and was removed on day 5 for TaqMan qPCR analysis of genes related to the\n                    <jats:italic>Wnt<\/jats:italic>\n                    pathway. A subset of bone was implanted s.c. into an athymic mouse, representing our xenograft model, and treated (25\u2009mg\/kg\u2009s.c. 2\u00d7\/week for 2\/4\u2009weeks). Implanted OI bone was evaluated using \u03bcCT and histomorphometry. Expression of\n                    <jats:italic>Wnt\/Wnt<\/jats:italic>\n                    \u2010related targets varied among untreated OI bone isolates. When treated with SclAb, OI bone showed an upregulation in osteoblast and osteoblast progenitor markers, which was heterogeneous across tissue. Interestingly, the greatest magnitude of response generally corresponded to samples with low untreated expression of progenitor markers. Conversely, samples with high untreated expression of these markers showed a lower response to treatment. in vivo implanted OI bone showed a bone\u2010forming response to SclAb via \u03bcCT, which was corroborated by histomorphometry. SclAb induced downstream\n                    <jats:italic>Wnt<\/jats:italic>\n                    targets\n                    <jats:italic>WISP1<\/jats:italic>\n                    and\n                    <jats:italic>TWIST1<\/jats:italic>\n                    , and elicited a compensatory response in\n                    <jats:italic>Wnt<\/jats:italic>\n                    inhibitors\n                    <jats:italic>SOST<\/jats:italic>\n                    and\n                    <jats:italic>DKK1<\/jats:italic>\n                    in OI bone with the greatest magnitude from OI cortical bone. Understanding patients' genetic, cellular, and morphological bone phenotypes may play an important role in predicting treatment response. This information may aid in clinical decision\u2010making for pharmacological interventions designed to address fragility in OI. \u00a9 2020 The Authors.\n                    <jats:italic>JBMR Plus<\/jats:italic>\n                    published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.\n                  <\/jats:p>","DOI":"10.1002\/jbm4.10377","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T09:20:39Z","timestamp":1590484839000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Gene Expression Profile and Acute Gene Expression Response to Sclerostin Inhibition in Osteogenesis Imperfecta Bone"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7614-4412","authenticated-orcid":false,"given":"Rachel K","family":"Surowiec","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle S","family":"Caird","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1108-7258","authenticated-orcid":false,"given":"Kenneth M","family":"Kozloff","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor MI USA"},{"name":"Department of Orthopaedic Surgery University of Michigan  Ann Arbor MI 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