Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model

Wei Hu; Jia-Wu Liang; Song Liao; Zhi-Dong Zhao; Yu-Xing Wang; Xiao-Fei Mao; Si-Wei Hao; Yi-Fan Wang; Heng Zhu; Bin Guo

doi:10.1186/s40779-021-00355-y

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Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model

RESEARCH | Updated：2023-02-28

- Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model
- Military Medical Research Vol. 9, Issue 3, Pages: 319-330(2022)
- Affiliations：
  
  1.Medical School of Chinese People’s Liberation Army (PLA), Beijing 100853, China
  2.Department of Stomatology, the First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
  3.Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100840, China
- Author bio：
  
  * zhudingdingabc@163.com;
  guobin1110@126.com
- Funds：
- DOI：10.1186/s40779-021-00355-y
  CLC：
- Published：2022-06
- Accepted：
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Hu et al.: Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model. Mil Med Res, 2021, 8: 61.
DOI：

Hu et al.: Melatonin attenuates radiation-induced cortical bone-derived stem cells injury and enhances bone repair in postradiation femoral defect model. Mil Med Res, 2021, 8: 61. DOI： 10.1186/s40779-021-00355-y.

摘要

Abstract

Background:

The healing of bone defects can be challenging for clinicians to manage

especially after exposure to ionizing radiation. In this regard

radiation therapy and accidental exposure to gamma (γ)-ray radiation have been shown to inhibit bone formation and increase the risk of fractures. Cortical bone-derived stem cells (CBSCs) are reportedly essential for osteogenic lineages

bone maintenance and repair. This study aimed to investigate the effects of melatonin on postradiation CBSCs and bone defect healing.

Methods:

CBSCs were extracted from C57BL/6 mice and were identified by flow cytometry. Then CBSCs were subjected to 6 Gy γ-ray radiation followed by treatment with various concentrations of melatonin. The effects of exogenous melatonin on the self-renewal and osteogenic capacity of postradiation CBSCs

in vitro

were analyzed. The underlying mechanisms involved in genomic stability

apoptosis and oxidative stress-related signaling were further analyzed by Western blotting

flow cytometry and immunofluorescence assays. Moreover

postradiation femoral defect models were established and treated with Matrigel and melatonin. The effects of melatonin on postradiation bone healing

in vivo

were evaluated by micro-CT and pathological analysis.

Results:

The decrease in radiation-induced self-renewal and osteogenic capacity were partially reversed in postradiation CBSCs treated with melatonin (

0.05). Melatonin maintained genomic stability

reduced postradiation CBSC apoptosis and intracellular oxidative stress

and enhanced expression of antioxidant-related enzymes (

0.05). Western blotting validated the anti-inflammatory effects of melatonin by downregulating interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels

via

the extracellular regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway. Melatonin was also found to exhibit antioxidant effects

via

NRF2 signaling.

In vivo

experiments demonstrated that the newly formed bone in the melatonin plus Matrigel group had higher trabecular bone volume per tissue volume (BV/TV) and bone mineral density values with lower IL-6 and TNF-α levels than in the irradiation and the Matrigel groups (

0.05).

Conclusions:

This study suggested that melatonin could protect CBSCs against γ-ray radiation and assist in the healing of postradiation bone defects.

关键词

Keywords

references

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