{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T15:33:23Z","timestamp":1793806403128,"version":"4.6.1"},"reference-count":104,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R15HL121786"],"award-info":[{"award-number":["R15HL121786"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014807","name":"Cancer Research Coordinating Committee","doi-asserted-by":"publisher","award":["CRR-13-201415"],"award-info":[{"award-number":["CRR-13-201415"]}],"id":[{"id":"10.13039\/100014807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Romosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved for treatment of postmenopausal women with osteoporosis at a high risk for fracture. Previous work in sclerostin global knockout (Sost\u2212\/\u2212) mice indicated alterations in immune cell development in the bone marrow (BM), which could be a possible side effect in romosozumab-treated patients. Here, we examined the effects of short-term sclerostin depletion in the BM on hematopoiesis in young mice receiving sclerostin antibody (Scl-Ab) treatment for 6 weeks, and the effects of long-term Sost deficiency on wild-type (WT) long-term hematopoietic stem cells transplanted into older cohorts of Sost\u2212\/\u2212 mice. Our analyses revealed an increased frequency of granulocytes in the BM of Scl-Ab-treated mice and WT\u2192Sost\u2212\/\u2212 chimeras, indicating myeloid-biased differentiation in Sost-deficient BM microenvironments. This myeloid bias extended to extramedullary hematopoiesis in the spleen and was correlated with an increase in inflammatory cytokines TNF\u03b1, IL-1\u03b1, and MCP-1 in Sost\u2212\/\u2212 BM serum. Additionally, we observed alterations in erythrocyte differentiation in the BM and spleen of Sost\u2212\/\u2212 mice. Taken together, our current study indicates novel roles for Sost in the regulation of myelopoiesis and control of inflammation in the BM.<\/jats:p>","DOI":"10.3390\/ijms22179111","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T22:12:22Z","timestamp":1629843142000},"page":"9111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Cristine","family":"Donham","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"},{"name":"Quantitative and Systems Biology Graduate Program, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betsabel","family":"Chicana","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"},{"name":"Quantitative and Systems Biology Graduate Program, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Robling","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Roudebush VA Medical Center, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonny","family":"Elizaldi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Millan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"},{"name":"Quantitative and Systems Biology Graduate Program, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa K.","family":"Murugesh","sequence":"additional","affiliation":[{"name":"Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1605-3193","authenticated-orcid":false,"given":"Nicholas R.","family":"Hum","sequence":"additional","affiliation":[{"name":"Quantitative and Systems Biology Graduate Program, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"},{"name":"Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7822-7040","authenticated-orcid":false,"given":"Aimy","family":"Sebastian","sequence":"additional","affiliation":[{"name":"Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9546-5561","authenticated-orcid":false,"given":"Gabriela G.","family":"Loots","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"},{"name":"Quantitative and Systems Biology Graduate Program, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"},{"name":"Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer O.","family":"Manilay","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"},{"name":"Quantitative and Systems Biology Graduate Program, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/hmg\/10.5.537","article-title":"Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)","volume":"10","author":"Balemans","year":"2001","journal-title":"Hum. 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