Inflammatory bone loss associated with MFG‐E8 deficiency is rescued by teriparatide
| العنوان: | Inflammatory bone loss associated with MFG‐E8 deficiency is rescued by teriparatide |
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| المؤلفون: | J. Ignacio Aguirre, Laura E. Zweifler, Kamran Atabai, Erica M. Siismets, Benjamin P. Sinder, Anna L. Seydel, Amy J. Koh, Hernan Roca, Megan N. Michalski, Laurie K. McCauley |
| المصدر: | The FASEB Journal. 32:3730-3741 |
| بيانات النشر: | Wiley, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Anabolism, medicine.medical_treatment, Osteoporosis, Osteoclasts, Biochemistry, Proinflammatory cytokine, Apoptotic cell clearance, Mice, 03 medical and health sciences, 0302 clinical medicine, Teriparatide, Internal medicine, Genetics, medicine, Animals, Molecular Biology, Cells, Cultured, Autoimmune disease, Bone Density Conservation Agents, Chemistry, Research, Growth factor, Milk Proteins, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Antigens, Surface, Female, Bone marrow, 030215 immunology, Biotechnology, medicine.drug |
| الوصف: | A prolonged increase in proinflammatory cytokines is associated with osteoporotic and autoimmune bone loss and, conversely, anti-inflammatory pathways are associated with protection against bone loss. Milk fat globule-epidermal growth factor (MFG-E)-8 is a glycoprotein that is proresolving, regulates apoptotic cell clearance, and has been linked to autoimmune disease and skeletal homeostasis. The role of MFG-E8 in the young vs. adult skeleton was determined in mice deficient in MFG-E8 (KO). In vivo, trabecular bone was similar in MFG-E8KO and wild-type (WT) mice at 6 and 16 wk, whereas 22 wk adult MFG-E8KO mice displayed significantly reduced trabecular BV/TV. The number of osteoclasts per bone surface was increased in 22-wk MFG-E8 KO vs. WT mice, and recombinant murine MFG-E8 decreased the number and size of osteoclasts in vitro. Adult MFG-E8KO spleen weight:body weight was increased compared with WT, and flow cytometric analysis showed significantly increased myeloid-derived suppressor cells (CD11b(hi)GR-1(+)) and neutrophils (CD11b(hi)Ly6G(+)) in MFG-E8KO bone marrow, suggesting an inflammatory phenotype. PTH-treated MFG-E8KO mice showed a greater anabolic response (+124% BV/TV) than observed in PTH-treated WT mice (+64% BV/TV). These data give insight into the role of MFG-E8 in the adult skeleton and suggest that anabolic PTH may be a valuable therapeutic approach for autoimmune-associated skeletal disease.—Michalski, M. N., Seydel, A. L., Siismets, E. M., Zweifler, L. E., Koh, A. J., Sinder, B. P., Aguirre, J. I., Atabai, K., Roca, H., McCauley, L. K. Inflammatory bone loss associated with MFG-E8 deficiency is rescued by teriparatide. |
| تدمد: | 1530-6860 0892-6638 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9d06306e8eb1e0bf2c5e55c7b8e77d04 https://doi.org/10.1096/fj.201701238r |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9d06306e8eb1e0bf2c5e55c7b8e77d04 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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