Calorie restriction induces mandible bone loss by regulating mitochondrial function

Caloric restriction (CR), commonly used as both a lifestyle choice and medical strategy, has been shown to adversely impact appendicular bone mass. However, its influence on alveolar bone health and the underlying mechanisms remain poorly understood. In this study, 8-week-old C57BL/6 J mice were fed with 30 % CR for 8 weeks. Micro-architecture, histologic parameters, and in vitro trajectories of osteoblast and adipocyte differentiation were examined. To further explore the underlying mechanisms, metabolic cages and in vitro bioenergetics were performed. Our results showed that 8 weeks of CR led to trabecular and cortical bone loss in the mandibles of female mice. CR in female mice decreased bone formation and bone resorption activities but induced adiposity in the mandibles. After CR, the adipogenesis in mesenchymal cells from orofacial bones (OMSCs) was greatly accelerated, whereas osteogenic differentiation was reduced in females. Undifferentiated CR OMSCs showed marked suppression in ATP production rates from mitochondria in female mice. ATP production rates decreased after osteogenesis but were upregulated during adipogenesis in female mice. Conversely, the generation of reactive oxygen species (ROS) was heightened during both osteoblastic and adipogenic differentiation in female CR groups. Collectively, our study indicated that CR could cause significant bone loss in the mandibles of female mice, almost certainly related to a reduced ATP supply and the unregulated generation of ROS.