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Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis in vitro

  • Authors:
    • Yuyang Wang
    • Linshan Xu
    • Jianping Wang
    • Jiangtao Bai
    • Jianglong Zhai
    • Guoying Zhu
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    Affiliations: Department of Radiation Protection, Institute of Radiation Medicine, Fudan University, Shanghai 200032, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 76
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    Published online on: March 5, 2021
       https://doi.org/10.3892/ijmm.2021.4909
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Abstract

Irradiation‑induced bone remodeling imbalances arise as a consequence of the dysregulation of bone formation and resorption. Due to the abundance of osteocytes, their long life and their dual‑regulatory effects on both osteoblast and osteoclast function, they serve as critical coordinators of bone remolding. In the present study, femur and tibia‑derived primary osteocytes were cultured and irradiated to observe the functional changes and the cellular senescence phenotype in vitro. Irradiation directly reduced cell viability, affected the crucial dendritic morphology and altered the expression of functional proteins, including upregulation of receptor activator of nuclear factor‑κB ligand and sclerostin, and downregulation of osteoprotegerin. Irradiated osteocytes were shown to exhibit notable DNA damage, which resulted in the initiation of a typical cellular senescence phenotype. Furthermore, it was found that irradiation‑induced prematurely senescent osteocytes stimulate molecular secretion, referred to as senescence‑associated secretory phenotype (SASP), which may be involved in modulation of the bone microenvironment, including the promotion of osteoclastogenesis. Taken together, the results showed that irradiation triggered osteocyte senescence and the acquisition of an associated secretory phenotype. This further resulted in an imbalance of bone remodeling through senescent influence on proliferation, morphology and marker protein production, but also indirectly via a paracrine pathway through SASP secretion. The results of the present study may highlight the potential of SASP‑targeted interventions for the management of radiation‑induced bone loss.
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Copy and paste a formatted citation
Spandidos Publications style
Wang Y, Xu L, Wang J, Bai J, Zhai J and Zhu G: Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis <em>in vitro</em>. Int J Mol Med 47: 76, 2021.
APA
Wang, Y., Xu, L., Wang, J., Bai, J., Zhai, J., & Zhu, G. (2021). Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis <em>in vitro</em>. International Journal of Molecular Medicine, 47, 76. https://doi.org/10.3892/ijmm.2021.4909
MLA
Wang, Y., Xu, L., Wang, J., Bai, J., Zhai, J., Zhu, G."Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis <em>in vitro</em>". International Journal of Molecular Medicine 47.5 (2021): 76.
Chicago
Wang, Y., Xu, L., Wang, J., Bai, J., Zhai, J., Zhu, G."Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis <em>in vitro</em>". International Journal of Molecular Medicine 47, no. 5 (2021): 76. https://doi.org/10.3892/ijmm.2021.4909
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Y, Xu L, Wang J, Bai J, Zhai J and Zhu G: Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis <em>in vitro</em>. Int J Mol Med 47: 76, 2021.
APA
Wang, Y., Xu, L., Wang, J., Bai, J., Zhai, J., & Zhu, G. (2021). Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis <em>in vitro</em>. International Journal of Molecular Medicine, 47, 76. https://doi.org/10.3892/ijmm.2021.4909
MLA
Wang, Y., Xu, L., Wang, J., Bai, J., Zhai, J., Zhu, G."Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis <em>in vitro</em>". International Journal of Molecular Medicine 47.5 (2021): 76.
Chicago
Wang, Y., Xu, L., Wang, J., Bai, J., Zhai, J., Zhu, G."Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis <em>in vitro</em>". International Journal of Molecular Medicine 47, no. 5 (2021): 76. https://doi.org/10.3892/ijmm.2021.4909
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