Back to Search Start Over

Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice

Authors :
Deepa K. Murugesh
Nicholas R. Hum
Cristine Donham
Alberto J. Millan
Sonny R. Elizaldi
Alexander G. Robling
Asmaa Mohamed
Aimy Sebastian
Michael Chi
Gabriela G. Loots
Jennifer O. Manilay
Brian Freeman
Betsabel Chicana
Source :
International journal of molecular sciences, vol 22, iss 17, International Journal of Molecular Sciences, Volume 22, Issue 17, International Journal of Molecular Sciences, Vol 22, Iss 9111, p 9111 (2021)
Publication Year :
2021
Publisher :
eScholarship, University of California, 2021.

Abstract

Romosozumab, 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.

Details

Database :
OpenAIRE
Journal :
International journal of molecular sciences, vol 22, iss 17, International Journal of Molecular Sciences, Volume 22, Issue 17, International Journal of Molecular Sciences, Vol 22, Iss 9111, p 9111 (2021)
Accession number :
edsair.doi.dedup.....d56498d00e8fed28c2cbd01f915b3321