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. 2021 Apr;36(4):803-813.
doi: 10.1002/jbmr.4245. Epub 2021 Feb 8.

Severity of Megakaryocyte-Driven Osteosclerosis in Mpig6b-Deficient Mice Is Sex-Linked

Mariya Stavnichuk  1   2 , Josephine T Tauer  2   3 , Zoltan Nagy  4 , Alexandra Mazharian  5 , Mélanie Welman  6 , Marie Lordkipanidzé  6   7 , Yotis A Senis  5 , Svetlana V Komarova  1   2   3
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Free article

Severity of Megakaryocyte-Driven Osteosclerosis in Mpig6b-Deficient Mice Is Sex-Linked

Mariya Stavnichuk et al. J Bone Miner Res. 2021 Apr.
Free article

Abstract

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-/- ) mice. Although male and female Mpig6b-/- mice presented with elevated bone marrow megakaryocyte number and macrothrombocytopenia, female Mpig6b-/- mice developed progressive splenomegaly starting at 8 weeks of age. Micro-computed tomography (μCT) of femurs showed that female Mpig6b-/- mice had increased cortical thickness and reduced bone marrow area starting at 8 weeks of age and developed occlusion of the medullary cavity by trabeculae by 16 weeks of age. In contrast, male Mpig6b-/- 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 weeks. Ovariectomy of 10-week-old female Mpig6b-/- mice prevented the development of medullary cavity osteosclerosis, whereas orchiectomy of male Mpig6b-/- mice did not exacerbate their disease. Importantly, ovariectomized female Mpig6b-/- mice also demonstrated improvement in spleen weight compared to sham-operated Mpig6b-/- mice, establishing estrogen as a contributing factor to the severity of the megakaryocyte-driven osteosclerosis. © 2021 American Society for Bone and Mineral Research (ASBMR).

Keywords: BONE μCT; OSTEOBLASTS; OSTEOCLASTS; OSTEOSCLEROSIS; SEX STEROIDS.

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References

    1. Psaila B, Lyden D, Roberts I. Megakaryocytes, malignancy and bone marrow vascular niches. JTH. 2012;10(2):177-88.
    1. Oon SF, Singh D, Tan TH, et al. Primary myelofibrosis: spectrum of imaging features and disease-related complications. Insights Imaging. 2019;10(1):71.
    1. Steer K, Stavnichuk M, Morris M, Komarova SV. Bone health in patients with hematopoietic disorders of bone marrow origin: systematic review and meta- analysis. J Bone Miner Res. 2017;32(4):731-42.
    1. Malara A, Abbonante V, Zingariello M, Migliaccio A, Balduini A. Megakaryocyte contribution to bone marrow fibrosis: many arrows in the quiver. Mediterr J Hematol Infect Dis. 2018;10(1):e2018068.
    1. Mazharian A, Wang YJ, Mori J, et al. Mice lacking the ITIM-containing receptor G6b-B exhibit macrothrombocytopenia and aberrant platelet function. Sci Signal. 2012;5(248):ra78.

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