Osteocyte Apoptosis Contributes to Cold Exposure-induced Bone Loss.

Jingke Du,Junqi Cui,Mingming Xu,Zhifeng Yu,Xinhua Qu,Hanjun Li,Mengning Yan,Zihao He,Shuhong Zhang,Shuangyan Zhang

doi:10.3389/fbioe.2021.733582

Abstract

Emerging evidence indicates that bone mass is regulated by systemic energy balance. Temperature variations have profound effects on energy metabolism in animals, which will affect bone remodeling. But the mechanism remains unclear. 2-month-old C57BL/6J male mice were exposed to cold (4°C) and normal (23°C) temperatures for 28 days and the effects of cold exposure on bone mass was investigated. Micro-computed tomography results showed that bone volume fraction was significantly reduced after 14 days of exposure to cold temperature, and it was recovered after 28 days. Ploton silver staining and immunohistochemical results further revealed that exposure to cold decreased canalicular length, number of E11-and MMP13-positive osteocytes after 14 days, but they returned to the baseline levels after 28 days, different from the normal temperature control group. In addition, change of Caspase-3 indicated that exposure to cold temperature augmented apoptosis of osteocytes. In vitro results confirmed the positive effect of brown adipocytes on osteocyte‘s dendrites and E11 expression. In conclusion, our findings indicate that cold exposure can influence bone mass in a time-dependent manner, with bone mass decreasing and recovering at 2 and 4 weeks respectively. The change of bone mass may be caused by the apoptosis osteocytes. Brown adipocyte tissue could influence bone remodeling through affecting osteocyte.

Highlights

Bone mass can be influenced by energy balance in many ways, and studies have demonstrated that caloric restriction and changes in leptin levels result in reduction of bone mass (Shi et al, 2008; Devlin et al, 2010)
The trabecular thickness (Tb.Th) was found to be lower at 14 days in the mice belonging to the cold-stress group than in the control group, which is consistent with the increased trabecular separation (Tb.Sp)
There was no significant change in the body weight of the mice over time. These results indicate that stimulation with cold temperature has a negative effect on the bone mass after short-term cold

Summary

Introduction

Bone mass can be influenced by energy balance in many ways, and studies have demonstrated that caloric restriction and changes in leptin levels result in reduction of bone mass (Shi et al, 2008; Devlin et al, 2010). Further studies have revealed that cold temperature can activate the sympathetic nerves, which promote non-shivering thermogenesis of the muscle and have a deleterious effect on bone mineral density (Bonnet et al, 2007; Chen et al, 2019). Wee et al have shown that exposure to cold decreases bone mass in the neuropeptide Y (NPY) wild-type mice, whereas the absence of NPY in the null mice obliterates these changes in bone mineral density (Wee et al, 2020). Steinberg et al have found that the bone diameter and cortical thickness in the femoral midshaft decreased significantly after 69 days but increased after

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Conclusion