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Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice
- 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.
- Subjects :
- Male
Aging
Myeloid
chemistry.chemical_compound
Mice
Gene Knockout Techniques
Bone Marrow
Erythrocyte differentiation
Monoclonal
Biology (General)
Spectroscopy
Mice, Knockout
Myelopoiesis
genetic animal models
Antibodies, Monoclonal
Adaptor Proteins
General Medicine
Hematology
Computer Science Applications
Extramedullary hematopoiesis
Chemistry
Haematopoiesis
medicine.anatomical_structure
Cytokines
Female
Stem Cell Research - Nonembryonic - Non-Human
osteopetrosis
medicine.medical_specialty
QH301-705.5
Knockout
Romosozumab
Catalysis
Article
Antibodies
Inorganic Chemistry
Internal medicine
medicine
Genetics
Animals
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
Adaptor Proteins, Signal Transducing
Inflammation
osteoimmunology
Chemical Physics
business.industry
Organic Chemistry
aging
Signal Transducing
medicine.disease
Hematopoietic Stem Cells
Stem Cell Research
Endocrinology
chemistry
Sclerostin
Osteoporosis
Bone marrow
Other Biological Sciences
business
Other Chemical Sciences
Subjects
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