Alleviative Effects of Exercise on Bone Remodeling in Fluorosis Mice.

Fluorine is widely present in nature in the form of fluoride. Prolonged high-dose fluoride exposure can cause skeletal fluorosis, resulting in osteosclerosis, osteoporosis or osteomalacia. It has been proved that exercise is one of the important factors affecting the health of the bone and promoting bone formation. To investigate the effects of exercise on bone remodeling in fluorosis mice, 120 male 3-week-old ICR mice were randomly divided into four groups: control group (C), exercise group (E), fluoride group (F), fluoride plus exercise group (F + E). After 8-week physical exercise and/or fluoride exposure, we evaluated the content of fluorine, the histopathological structure and microstructure of femur, bone metabolism biochemical indexes and oxidative stress related parameters, and the mRNA and protein levels of genes in BMP-2/Smads and OPG/RANKL/RANK signaling pathways. Our results showed that 100 mg/L NaF exposure increased the accumulation of fluoride in bone, altered histology of bone, and enhanced the activities of ALP and TRACP. Meanwhile, excessive fluoride induced oxidative stress in bone tissue by increasing the content of ROS and MDA, and decreasing the activities of antioxidant enzymes. In addition, the results of qRT-PCR suggested that NaF significantly increased the mRNA expression of BMP-2, Smad-5, Col IA1, Col IA2, OPG, RANKL and RANK, as well as the elevated proteins of OPG, RANKL and RANK. However, these fluoride-induced changes were alleviated after moderate exercise. Taken together, these findings indicated that moderate exercise decreased the toxicity of fluoride by reducing the accumulation of fluorine in the body to relieve the bone damage caused by fluorosis.