Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism
| Autor: | Brianne S Thicke, Ming Ruan, Aleksey V. Matveyenko, Jennifer R. Geske, Merry Jo Oursler, Amanda J Tweed, David G. Monroe, Bart L. Clarke, Brittany A. Eckhardt, Thomas Levin Andersen, Joshua N. Farr, Chee Kian Chew, Matthew T. Drake, Sundeep Khosla, Adrian Vella, Robert A. Rizza, Elizabeth J. Atkinson, Moustapha Kassem, Louise K. McCready, Megan M. Weivoda |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
General Physics and Astronomy Osteoclasts Bone remodeling 0302 clinical medicine Glucose homeostasis Prospective Studies lcsh:Science Aged 80 and over Multidisciplinary Osteoblast Middle Aged Resorption medicine.anatomical_structure Denosumab Female Bone Remodeling medicine.drug musculoskeletal diseases medicine.medical_specialty Science Dipeptidyl Peptidase 4 education chemistry.chemical_element 030209 endocrinology & metabolism Calcium General Biochemistry Genetics and Molecular Biology Bone resorption Bone and Bones Article 03 medical and health sciences Osteoclast Internal medicine medicine Animals Humans Bone Aged Osteoblasts Tumor Suppressor Proteins Calcium-Binding Proteins General Chemistry Repressor Proteins 030104 developmental biology Endocrinology chemistry Diabetes Mellitus Type 2 Osteoporosis lcsh:Q Energy Metabolism |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) Weivoda, M M, Chew, C K, Monroe, D G, Farr, J N, Atkinson, E J, Geske, J R, Eckhardt, B, Thicke, B, Ruan, M, Tweed, A J, McCready, L K, Rizza, R A, Matveyenko, A, Kassem, M, Andersen, T L, Vella, A, Drake, M T, Clarke, B L, Oursler, M J & Khosla, S 2020, ' Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism ', Nature Communications, vol. 11, 87 . https://doi.org/10.1038/s41467-019-14003-6 |
| ISSN: | 2041-1723 |
| Popis: | Bone remodeling consists of resorption by osteoclasts followed by formation by osteoblasts, and osteoclasts are a source of bone formation-stimulating factors. Here we utilize osteoclast ablation by denosumab (DMAb) and RNA-sequencing of bone biopsies from postmenopausal women to identify osteoclast-secreted factors suppressed by DMAb. Based on these analyses, LIF, CREG2, CST3, CCBE1, and DPP4 are likely osteoclast-derived coupling factors in humans. Given the role of Dipeptidyl Peptidase-4 (DPP4) in glucose homeostasis, we further demonstrate that DMAb-treated participants have a significant reduction in circulating DPP4 and increase in Glucagon-like peptide (GLP)-1 levels as compared to the placebo-treated group, and also that type 2 diabetic patients treated with DMAb show significant reductions in HbA1c as compared to patients treated either with bisphosphonates or calcium and vitamin D. Thus, our results identify several coupling factors in humans and uncover osteoclast-derived DPP4 as a potential link between bone remodeling and energy metabolism. Anti-resorptive bone therapies also inhibit bone formation, as osteoclasts secrete factors that stimulate bone formation by osteoblasts. Here, the authors identify osteoclast-secreted factors that couple bone resorption to bone formation in healthy subjects, and show that osteoclast-derived DPP4 may be a factor coupling bone resorption to energy metabolism. |
| Databáze: | OpenAIRE |
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