Influence of Exercise on Bone Remodeling-Related Hormones and Cytokines in Ovariectomized Rats: A Model of Postmenopausal Osteoporosis

Abstract

This study aims to explore the effects of exercise on postmenopausal osteoporosis and the mechanisms by which exercise affects bone remodeling. Sixty-three Wistar female rats were randomly divided into five groups: (1) control group, (2) sham-operated group, (3) OVX (Ovariectomy) group, (4) DES-OVX (Diethylstilbestrol-OVX) group, and (5) Ex-OVX (Exercise-OVX) group. The rat osteoporosis model was established through ovariectomy. The Ex-OVX rats were made to run 251.2 meters every day, 6 d/wk for 3 months in a running wheel. Trabecular bone volume (TBV%), total resorption surface (TRS%), trabecular formation surface (TFS%), mineralization rate (MAR), bone cortex mineralization rate (mAR), and osteoid seam width (OSW) were determined by bone histomorphometry. The mRNA and protein levels of interleukin-1β (IL-1β2), interleukin-6 (IL-6), and cyclooxygenase-2 (Cox-2) were determined by in situ hybridization and immunohistochemistry, respectively. Serum levels of estrogen estradiol (E2), calcitonin (CT), osteocalcin (BGP), and parathyroid hormone (PTH) were determined by ELISA assays. The investigation revealed that compared to the control and the sham-operated groups, the OVX group showed significantly lower levels of TBV%, E2, and CT, but much higher levels of TRS%, TFS%, MAR, OSW, BGP, and PTH. The Ex-OVX group showed increased TBV% and serum levels of E2 and CT compared to the OVX group. Ovariectomy also led to a significant increase in IL-1β mRNA and protein levels in the bone marrow and IL-6 and Cox-2 protein levels in tibias. In addition, the Ex-OVX group showed lower levels of IL-1 mRNA and protein, IL-6 mRNA, and Cox-2 mRNA and protein than those in the OVX group. The upshot of the study suggests that exercise can significantly increase bone mass in postmenopausal osteoporosis rat models by inhibiting bone resorption and increasing bone formation, especially in trabecular bones.

Reduced expression of CRHR2 and Sp-1 in myocardium of ovariectomized rats is improved by exercise training

“…Exercise has been shown to stimulate estrogenic-like effects on expression of genes in various tissues and ameliorates the negative changes caused by estrogen deficiency, which might be attributed to, at least in part, an increase of estrogen level [19][20][21][22]. Our previous have demonstrated that expression of CRHR2 and Sp-1 in myocardium is regulated by estrogen.…”

MiR-214 Attenuates the Osteogenic Effects of Mechanical Loading on Osteoblasts

“…In vivo studies have shown that exercise increases bone mass, BMD and bone strength, and improves bone microstructure in both humans and animals [7,[26][27][28]. In vitro studies have also reported that mechanical loading enhances osteogenic differentiation and inhibits bone resorption through regulating bone anabolic and anti-catabolic gene expression, thus improving bone metabolism and promoting bone formation [9,29,30].…”

Connecting the Dots: Linking Osteocyte Activity and Therapeutic Modulation of Sclerostin by Extending a Multiscale Systems Model

“…OCY undergoing apoptosis also secrete interleukin (IL)−1 and IL‐6, which promote osteoclastogenesis and provide another layer of feedback control that is not yet represented in the model. OB are also a source of IL‐6, as well as macrophage‐colony‐stimulating factor (M‐CSF), which also contributes to osteoclastogenesis . Supporting data are needed to fully characterize effects of sclerostin mAb on changes in CTx, as even the PBO arms show relatively large fluctuations in CTx over several months …”

“…33 This feedback mechanism needs to be fully elucidated by experimental data before implementation into the model. OCY undergoing apoptosis also secrete interleukin (IL)21 and IL-6, which promote osteoclastogenesis 34 and provide another layer of feedback control that is not yet represented in the model. OB are also a source of IL-6, as well as macrophage-colony-stimulating factor (M-CSF), which also contributes to osteoclastogenesis.…”

“…OB are also a source of IL-6, as well as macrophage-colony-stimulating factor (M-CSF), which also contributes to osteoclastogenesis. 34 Supporting data are needed to fully characterize effects of sclerostin mAb on changes in CTx, as even the PBO arms show relatively large fluctuations in CTx over several months. 1,11,12 It was hypothesized that diminishing the pre-OB pool with sclerostin inhibition contributes to attenuation in boneformation activity after multiple doses.…”