Abstract:
:Mice with an overall deletion of the sensory neuropeptide α-calcitonin gene-related peptide (α-CGRP) develop an age-dependent osteopenic bone phenotype. Underlying molecular mechanisms of how αCGRP 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) α-CGRP-deficient mice (-/-) and age-matched WT controls. All WT bone cell cultures endogenously produced and secreted α-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 α-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 α-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) α-CGRP-deficient mice.
journal_name
Mech Ageing Devjournal_title
Mechanisms of ageing and developmentauthors
Niedermair T,Schirner S,Lasheras MG,Straub RH,Grässel Sdoi
10.1016/j.mad.2020.111265subject
Has Abstractpub_date
2020-07-01 00:00:00pages
111265eissn
0047-6374issn
1872-6216pii
S0047-6374(20)30061-0journal_volume
189pub_type
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journal_title:Mechanisms of ageing and development
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journal_title:Mechanisms of ageing and development
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journal_title:Mechanisms of ageing and development
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journal_title:Mechanisms of ageing and development
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