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Aberrant megakaryocyte function in bone marrow and spleen may affect bone cells through cell-cell contact or soluble factors. We aimed to assess the role of circulating factors produced by splenic cells in mediating osteosclerosis in\n                    <jats:italic>Mpig6b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice using splenectomy, a procedure commonly used in clinics. Splenectomy or sham surgery was performed on 32-week-old female\n                    <jats:italic>Mpig6b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    and littermate wildtype (WT) mice, when splenomegaly and long bone osteosclerosis were established. Twenty weeks later, the hematopoietic parameters and bone structure of the femur and lumbar vertebra were analyzed. Splenectomy significantly improved platelet count, but the larger platelet size persisted in\n                    <jats:italic>Mpig6b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. The\n                    <jats:italic>Mpig6b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    femurs with established osteosclerosis were not affected by splenectomy. In contrast, splenectomy prevented the development of osteosclerosis in vertebrae of\n                    <jats:italic>Mpig6b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Significant vertebral bone loss and increased circulating TRACP 5b were demonstrated in splenectomized\n                    <jats:italic>Mpig6b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice compared to sham-operated and WT mice. Using quantitative plasma proteomics, we identified intercellular adhesion molecule 2 (ICAM2) as significantly increased in\n                    <jats:italic>Mpig6b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice compared to WT and reversed to normal levels after splenectomy. The interaction of membrane-bound ICAM2 and MAC1 was reported to be critical for osteoclast fusion. Our in vitro study revealed that soluble recombinant ICAM2 dose-dependently inhibited osteoclast fusion, suggesting that competitive binding of MAC1 with soluble ICAM2 prevented its interaction with membrane-bound ICAM2. Thus, we identified the soluble ICAM2 as a novel inhibitor of osteoclast fusion and mediator of osteosclerosis in\n                    <jats:italic>Mpig6b<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice.\n                  <\/jats:p>","DOI":"10.1038\/s41413-026-00575-9","type":"journal-article","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T08:56:00Z","timestamp":1789894560000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spleen-derived circulating intercellular adhesion molecule 2 promotes osteosclerosis in chronic myelofibrosis"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2174-2319","authenticated-orcid":false,"given":"Sirion","family":"Aksornthong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Tiedemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Welman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Mazharian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7418-6766","authenticated-orcid":false,"given":"Marie","family":"Lordkipanidz\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yotis A.","family":"Senis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3570-3147","authenticated-orcid":false,"given":"Svetlana V.","family":"Komarova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"575_CR1","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1002\/ajh.26857","volume":"98","author":"A Tefferi","year":"2023","unstructured":"Tefferi, A. 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