Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice.

Autor: Donham C; Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA.; Quantitative and Systems Biology Graduate Program, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA., Chicana B; Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA.; Quantitative and Systems Biology Graduate Program, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA., Robling AG; Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.; Roudebush VA Medical Center, Indianapolis, IN 46202, USA., Mohamed A; Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA., Elizaldi S; Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA., Chi M; Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA., Freeman B; Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA., Millan A; Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA.; Quantitative and Systems Biology Graduate Program, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA., Murugesh DK; Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA., Hum NR; Quantitative and Systems Biology Graduate Program, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA.; Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA., Sebastian A; Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA., Loots GG; Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA.; Quantitative and Systems Biology Graduate Program, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA.; Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA., Manilay JO; Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA.; Quantitative and Systems Biology Graduate Program, University of California, Merced, 5200 North Lake Road, Merced, CA 95343, USA.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2021 Aug 24; Vol. 22 (17). Date of Electronic Publication: 2021 Aug 24.
DOI: 10.3390/ijms22179111
Abstrakt: 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.
Databáze: MEDLINE