Severity of Megakaryocyte‐Driven Osteosclerosis in <scp> <i>Mpig6b</i> </scp> ‐Deficient Mice Is Sex‐Linked

Patients with chronic myelofibrosis often suffer from osteosclerosis, which is associated bone pain and may lead to marrow failure. The pathogenesis of linked aberrant megakaryocyte development function. Null loss-of-function mutations in MPIG6B, codes for the inhibitory heparan sulfate receptor G6b-B, result severe macrothrombocytopenia, large clusters, focal primary mice humans. We investigated osteosclerosis Mpig6b null (Mpig6b−/−) mice. Although male female Mpig6b−/− presented elevated number developed progressive splenomegaly starting at 8 weeks age. Micro–computed tomography (μCT) femurs showed that had increased cortical thickness reduced area age occlusion medullary cavity by trabeculae 16 In contrast, only a small proximal diaphysis demonstrated temporary decrease volume fraction trabecular weeks. Ovariectomy 10-week-old prevented whereas orchiectomy did not exacerbate their disease. Importantly, ovariectomized also improvement spleen weight compared sham-operated mice, establishing estrogen as contributing factor severity megakaryocyte-driven osteosclerosis. © 2021 American Society Bone Mineral Research (ASBMR).