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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-1? (IL-1?2), 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-1? 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.

SUBMITTER: Li L

PROVIDER: S-EPMC4231162 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis.

Li Lihui L Chen Xi X Lv Shuang S Dong Miaomiao M Zhang Li L Tu Jiaheng J Yang Jie J Zhang Lingli L Song Yinan Y Xu Leiting L Zou Jun J

PloS one 20141113 11

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 ...[more]

PMID: 25393283

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Project description:Cortex Eucommiae is used worldwide in traditional medicine, various constituents of Cortex Eucommiae, such as chlorogenic acid (CGA), has been reported to exert anti-osteoporosis activity in China, but the mechanism about their contribution to the overall activity is limited. The aims of this study were to determine whether chlorogenic acid can prevent estrogen deficiency-induced osteoporosis and to analyze the mechanism of CGA bioactivity. The effect of CGA on estrogen deficiency-induced osteoporosis was performed in vivo. Sixty female Sprague-Dawley rats were divided randomly among a sham-operated group and five ovariectomy (OVX) plus treatment subgroups: saline vehicle, 17?-ethinylestradiol (E2), or CGA at 9, 27, or 45 mg/kg/d. The rats' femoral metaphyses were evaluated by micro-computed tomography (?CT). The mechanism of CGA bioactivity was investigated in vitro. Bone mesenchymal stem cells (BMSCs) were treated with CGA, with or without phosphoinositide 3-kinase (PI3K) inhibitor LY294002. BMSCs proliferation and osteoblast differentiation were assessed with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and alkaline phosphatase, with or without Shp2 interfering RNA (RNAi). The results display that CGA at 27 and 45 mg/kg/day inhibited the decrease of bone mineral density (BMD) that induced by OVX in femur (p< 0.01), significantly promoted the levels of bone turnover markers, and prevented bone volume fraction (BV/TV), connectivity density (CoonD), trabecular number (Tb.N), trabecular thickness (Tb.Th) (all p< 0.01) to decrease and prevented the trabecular separation (Tb.Sp), structure model index (SMI)(both p< 0.01) to increase. CGA at 1 or 10 ?M enhanced BMSC proliferation in a dose-dependent manner. CGA at 0.1 to 10 ?M increased phosphorylated Akt (p-Akt) and cyclin D1. These effects were reversed by LY294002. CGA at 1 or 10 ?M increased BMSC differentiation to osteoblasts (p< 0.01), Shp2 RNAi suppressed CGA-induced osteoblast differentiation by decreasing Shp2, p-Akt, and cyclin D1. This study found that CGA improved the BMD and trabecular micro-architecture for the OVX-induced osteoporosis. Therefore, CGA might be an effective alternative treatment for postmenopausal osteoporosis. CGA promoted proliferation of osteoblast precursors and osteoblastic differentiation of BMSCs via the Shp2/PI3K/Akt/cyclin D1 pathway.

Project description:PurposeWe compared two different strategies providing professional coaching to administer an exercise program for women with postmenopausal osteoporosis (POP): individual training (IT) at home with trainer's supervision provided by telephone contacts at regular time-intervals or group training (GT) with trainer's live supervision. Our working hypothesis was that IT is a valid alternative to GT when GT is not feasible.Patients and methodsThis was a single-blind, randomized study. We recruited 52 women with POP, without significant comorbidity, and no participation in any structured exercise program within the previous 6 months. They were assigned randomly to IT or GT groups (n = 26 each). Distribution of age (IT: 68±4, GT: 67±8 years) and body mass index (IT: 23.0±2.5, GT: 21.4±5.1) was similar between groups. Each group performed the exercise program in two 1-hour sessions per week for 18 months. Primary outcome measure was Health-Related Quality of Life (HRQoL), as measured by the Short Osteoporosis Quality of Life Questionnaire. Secondary outcome measures focused on domains acknowledged to influence HRQoL (disability, fear of falling, weekly physical activity, physical function) or the effectiveness of the exercise program (retention, adherence, and safety). Significance level was set at p < 0.05.ResultsNo significant differences were observed between IT and GT groups for any domain. Retention, adherence, and safety were also similar. HRQoL, disability and fear of falling did not change between baseline and follow-up for either group. However, for both groups, physical function (knee flexion, shoulder mobility) and functional capacity (6-minute walking test) improved. Weekly physical activity levels increased from moderate range at baseline to intense at final assessment for both groups.ConclusionIT and GT supervised exercise programs for women with POP provide similar effectiveness, participation and safety. Hence, both modalities should be considered for future translation in clinical practice of exercise recommendations for POP.

Dataset Information

Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis.

Publications

Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis.

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