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10.08.2022 | Original Article

Defective bone repletion in aged Balb/cBy mice was caused by impaired osteoblastic differentiation

verfasst von: Matilda H. -C. Sheng, Kin-Hing William Lau, Charles H. Rundle, Anar Alsunna, Sean M. Wilson, David J. Baylink

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 6/2022

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Abstract

Introduction

This study was undertaken to gain mechanistic information about bone repair using the bone repletion model in aged Balb/cBy mice.

Materials and methods

one month-old (young) mice were fed a calcium-deficient diet for 2 weeks and 8 month-old (adult) and 21–25 month-old (aged) female mice for 4 weeks during depletion, which was followed by feeding a calcium-sufficient diet for 16 days during repletion. To determine if prolonged repletion would improve bone repair, an additional group of aged mice were repleted for 4 additional weeks. Control mice were fed calcium-sufficient diet throughout. In vivo bone repletion response was assessed by bone mineral density gain and histomorphometry. In vitro response was monitored by osteoblastic proliferation, differentiation, and senescence.

Results

There was no significant bone repletion in aged mice even with an extended repletion period, indicating an impaired bone repletion. This was not due to an increase in bone cell senescence or reduction in osteoblast proliferation, but to dysfunctional osteoblastic differentiation in aged bone cells. Osteoblasts of aged mice had elevated levels of cytosolic and ER calcium, which were associated with increased Cav1.2 and CaSR (extracellular calcium channels) expression but reduced expression of Orai1 and Stim1, key components of Stored Operated Ca²⁺ Entry (SOCE). Activation of Cav1.2 and CaSR leads to increased osteoblastic proliferation, but activation of SOCE is associated with osteoblastic differentiation.

Conclusion

The bone repletion mechanism in aged Balb/cBy mice is defective that is caused by an impaired osteoblast differentiation through reducedactivation of SOCE.

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Titel: Defective bone repletion in aged Balb/cBy mice was caused by impaired osteoblastic differentiation
verfasst von: Matilda H. -C. Sheng
Kin-Hing William Lau
Charles H. Rundle
Anar Alsunna
Sean M. Wilson
David J. Baylink
Publikationsdatum: 10.08.2022
Verlag: Springer Nature Singapore
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 6/2022
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-022-01361-3

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