Niedermair, Tanja and Schirner, Stephan and Lasheras, Mar Guaza and Straub, Rainer H. and Graessel, Susanne (2020) Absence of alpha-calcitonin gene-related peptide modulates bone remodeling properties of murine osteoblasts and osteoclasts in an age-dependent way. MECHANISMS OF AGEING AND DEVELOPMENT, 189: 111265. ISSN 0047-6374, 1872-6216
Full text not available from this repository. (Request a copy)Abstract
Mice with an overall deletion of the sensory neuropeptide alpha-calcitonin gene-related peptide (alpha-CGRP) develop an age-dependent osteopenic bone phenotype. Underlying molecular mechanisms of how alpha CGRP affects bone cell metabolism are not well understood. This study aims to characterize differences in metabolic parameters of osteoblast-like cells (OB) and differentiated bone marrow-derived macrophages (BMM)/osteoclast (OC) cultures isolated from 3 month (3 m) and 9 month old (9 m) alpha-CGRP-deficient mice (-/-) and age-matched WT controls. All WT bone cell cultures endogenously produced and secreted alpha-CGRP. We found higher BMM but reduced OB numbers and reduced OB vitality after isolation from 9 m compared to 3 m mice, independent of genotype. Absence of alpha-CGRP reduced cell spreading, increased apoptosis rate throughout osteogenic differentiation, and reduced ALP activity during late osteogenic differentiation in 9 m OB-/- cultures, whereas minor effects were found in 3 m OB-/- cultures. Cathepsin K activity was reduced in 3 m OC-/- cultures. On the contrary, 9 m OC-/- cells demonstrated increased proliferation and caspase3/7 activity. The absence of alpha CGRP influenced bone formation and resorption rate differently in bone cells from 3 and 9 m old mice. In summary we suggest, that an increase of dysfunctional mature osteoblasts might occur during aging and contribute to the development of the osteopenic bone phenotype in mature adult (9 m) alpha-CGRP-deficient mice.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SUBSTANCE-P; OSTEOGENIC DIFFERENTIATION; ALKALINE-PHOSPHATASE; NERVOUS-SYSTEM; LIFE-SPAN; IN-VITRO; TISSUE; PROLIFERATION; CGRP; RECEPTORS; Bone; Osteoblast; Osteoclast; alpha-Calcitonin gene-related peptide (alpha-CGRP); Osteopenia |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Orthopädie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Mar 2021 09:49 |
| Last Modified: | 19 Mar 2021 09:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44307 |
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