Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis in vitro
| العنوان: | Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis in vitro |
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| المؤلفون: | Guoying Zhu, Jianping Wang, Linshan Xu, Yuyang Wang, Jianglong Zhai, Jiangtao Bai |
| المصدر: | International Journal of Molecular Medicine |
| بيانات النشر: | Spandidos Publications, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Senescence, osteocyte, Osteocytes, Bone remodeling, Mice, Paracrine signalling, chemistry.chemical_compound, Osteoprotegerin, Osteoclast, Genetics, medicine, cellular senescence, Animals, osteoclastogenesis, Mice, Inbred BALB C, irradiation, Cell Differentiation, Osteoblast, Articles, General Medicine, Cell biology, medicine.anatomical_structure, chemistry, Gamma Rays, Osteocyte, senescence-associated secretory phenotype, Sclerostin |
| الوصف: | 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. |
| تدمد: | 1791-244X 1107-3756 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f0caa870a643790498f7badbb4404aa https://doi.org/10.3892/ijmm.2021.4909 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9f0caa870a643790498f7badbb4404aa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1791244X 11073756 |
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