{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T20:21:38Z","timestamp":1789935698172,"version":"4.0.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"4","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":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":69,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"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>Patients with chronic myelofibrosis often suffer from osteosclerosis, which is associated with bone pain and may lead to bone marrow failure. The pathogenesis of myelofibrosis is linked to aberrant megakaryocyte development and function. Null and loss-of-function mutations in MPIG6B, which codes for the inhibitory heparan sulfate receptor G6b-B, result in severe macrothrombocytopenia, large megakaryocyte clusters, and focal primary myelofibrosis in mice and humans. We investigated the development of osteosclerosis in Mpig6b null (Mpig6b\u2212\/\u2212) mice. Although male and female Mpig6b\u2212\/\u2212 mice presented with elevated bone marrow megakaryocyte number and macrothrombocytopenia, female Mpig6b\u2212\/\u2212 mice developed progressive splenomegaly starting at 8\u2009weeks of age. Micro\u2013computed tomography (\u03bcCT) of femurs showed that female Mpig6b\u2212\/\u2212 mice had increased cortical thickness and reduced bone marrow area starting at 8\u2009weeks of age and developed occlusion of the medullary cavity by trabeculae by 16\u2009weeks of age. In contrast, male Mpig6b\u2212\/\u2212 mice developed only a small number of trabeculae in the medullary cavity at the proximal diaphysis and demonstrated a temporary decrease in bone volume fraction and trabecular thickness at 16\u2009weeks. Ovariectomy of 10-week-old female Mpig6b\u2212\/\u2212 mice prevented the development of medullary cavity osteosclerosis, whereas orchiectomy of male Mpig6b\u2212\/\u2212 mice did not exacerbate their disease. Importantly, ovariectomized female Mpig6b\u2212\/\u2212 mice also demonstrated improvement in spleen weight compared to sham-operated Mpig6b\u2212\/\u2212 mice, establishing estrogen as a contributing factor to the severity of the megakaryocyte-driven osteosclerosis. \u00a9 2021 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4245","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T04:59:45Z","timestamp":1610686785000},"page":"803-813","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Severity of Megakaryocyte-Driven Osteosclerosis in Mpig6b-Deficient Mice Is Sex-Linked"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2436-7686","authenticated-orcid":false,"given":"Mariya","family":"Stavnichuk","sequence":"first","affiliation":[{"name":"Shriners Hospital for Children-Canada Montreal QC 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Montreal QC Canada"},{"name":"Research Center Montreal Heart Institute Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0947-9957","authenticated-orcid":false,"given":"Yotis A","family":"Senis","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Etablissement Fran\u00e7ais du Sang Grand Est, Unit\u00e9 Mixte de Recherche (UMR)-S 1255 F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3570-3147","authenticated-orcid":false,"given":"Svetlana V","family":"Komarova","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry McGill University Montreal QC Canada"},{"name":"Shriners Hospital for Children-Canada Montreal QC Canada"},{"name":"Department of Biological and Biomedical 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