Donham, CristineChicana, BetsabelRobling, Alexander G.Mohamed, AsmaaElizaldi, SonnyChi, MichaelFreeman, BrianMillan, AlbertoMurugesh, Deepa K.Hum, Nicholas R.Sebastian, AimyLoots, Gabriela G.Manilay, Jennifer O.2023-03-072023-03-072021-08-24Donham C, Chicana B, Robling AG, et al. Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice. Int J Mol Sci. 2021;22(17):9111. Published 2021 Aug 24. doi:10.3390/ijms22179111https://hdl.handle.net/1805/31649Romosozumab, 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−/−) 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−/− mice. Our analyses revealed an increased frequency of granulocytes in the BM of Scl-Ab-treated mice and WT→Sost−/− 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 TNFα, IL-1α, and MCP-1 in Sost−/− BM serum. Additionally, we observed alterations in erythrocyte differentiation in the BM and spleen of Sost−/− mice. Taken together, our current study indicates novel roles for Sost in the regulation of myelopoiesis and control of inflammation in the BM.en-USAttribution 4.0 InternationalOsteoimmunologyOsteopetrosisGenetic animal modelsAgingArticle