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.

Highlights

  • Postmenopausal osteoporosis (PMOP) is a common disease in middle-aged and elderly women, with a high incidence, significant harm, and difficult treatment

  • The body weight and fat content of the OVX + EX group were lower than the OVX group, while the muscle content and Bone Mineral Density (BMD) were significantly higher than the OVX group and significantly lower than sham operation (SHAM) group

  • These findings suggest that the ovariectomy led to an increase in body weight, body fat, and bone loss, while exercise helped to slow down the loss of muscle mass and bone density, partially mitigating the bone loss caused by the ovariectomy

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Summary

Introduction

Postmenopausal osteoporosis (PMOP) is a common disease in middle-aged and elderly women, with a high incidence, significant harm, and difficult treatment. A variety of immune cells originate in the bone marrow, and bone tissue cells share the same bone marrow microenvironment, regulatory factors, and receptors. Bone immunology revealed that the immune system, including T cells, B cells, and inflammatory cytokines, is a key regulator of osteoclasts and osteoblasts. T lymphocytes, B lymphocytes, cytokines, chemokines, and costimulatory molecules can all interact with osteoblasts and osteoclasts to jointly regulate bone formation and bone resorption, thereby regulating the bone remodeling process. Due to the limitation of bone mineralization and human bone tissue extraction, it is difficult to directly study the effect of exercise on the function of human bone cells. An RNA-seq bioinformatics analysis of the PBMCs was carried out to screen for genes sensitive to exercise that reflect bone changes. From the perspective of transcriptomics, the molecular mechanism of exercise in slowing down the bone loss caused by an estrogen deficiency in elderly women has been revealed, which provides a theoretical basis for exploring the molecular mechanism of exercise in delaying PMOP

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