The Effect of Moderate-Intensity Treadmill Exercise on Bone Mass and the Transcription of Peripheral Blood Mononuclear Cells in Ovariectomized Rats

Abstract

Objective: Using RNA-sequencing technology to screen the effect of moderate-intensity treadmill exercise on the sensitive genes that affect bone mass in the peripheral blood mononuclear cells (PBMCs) of ovariectomized (OVX) rats. Methods: Three-month-old female Sprague-Dawley rats of Specific Pathogen Free (SPF) grade were randomly divided into the sham operation (SHAM) group, OVX group, and OVX combined exercise (OVX + EX) group. The OVX + EX group performed moderate-intensity treadmill exercise for 17 weeks. Then, the body composition and bone mineral density (BMD) were measured, and the bone microstructure of the femur was observed. PBMCs were collected from the abdominal aorta, and the differential genes were analyzed by transcriptome sequencing to further screen sensitive genes. Results: (1) In the OVX group, the body weight and body fat content were significantly higher than in the SHAM group while the muscle content and BMD were significantly lower than the SHAM group. (2) The trabecular bone parameters in the OVX group were significantly lower than in the SHAM group, and they were significantly higher in the OVX + EX group than in the OVX group. When compared with the SHAM group, the microstructure of the distal femur trabecular in the OVX group was severely damaged, suggest that the morphological structure of trabecular bone is severely damaged, the number of trabecular bones is reduced, and the thickness becomes thinner, which lead to the widening of the trabecular bone space and the appearance of osteoporosis. The number and continuity of the trabecular bones were higher in the OVX + EX group than in the OVX group. (3) A Venn diagram showed that there were 58 common differential genes, and the differential genes were mainly enriched in the PI3K-Akt signaling pathway. Five sensitive genes were screened including CCL2, Nos3, Tgfb3, ITGb4, and LpL. The expression of CCL2, Nos3, and Tgfb3 genes was closely related to multiple bone parameters. Conclusion: Moderate-intensity treadmill exercise may improve the body composition and bone mass of the OVX group by upregulating CCL2 and other genes of the PBMC. The PBMCs in the peripheral blood can be a useful tool for monitoring the effect of exercise on bone health in postmenopausal osteoporosis.

Keywords: bone microstructure; bone mineral density; moderate intensity treadmill exercise; ovariectomized rats; peripheral blood mononuclear cells; transcriptome sequencing.