Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio

Postmenopausal diabetic women have a high risk of fractures. Salidroside has preventive effects on estrogen deficiency-induced osteoporosis and has hypoglycemic effects on diabetes in rats. However, whether salidroside inhibits bone loss in postmenopausal diabetic patients is still unknown. Here, we...

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Main Authors: Hongxing Zheng, Shanshan Qi, Chen Chen
Format: Article
Language:English
Published: MDPI AG 2018-09-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/23/9/2398
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author Hongxing Zheng
Shanshan Qi
Chen Chen
author_facet Hongxing Zheng
Shanshan Qi
Chen Chen
author_sort Hongxing Zheng
collection DOAJ
description Postmenopausal diabetic women have a high risk of fractures. Salidroside has preventive effects on estrogen deficiency-induced osteoporosis and has hypoglycemic effects on diabetes in rats. However, whether salidroside inhibits bone loss in postmenopausal diabetic patients is still unknown. Here, we established a rat model of osteoporosis to investigate the protective effects of salidroside on bone loss induced by ovariectomy combined with diabetes, also investigating the underlying mechanisms. Two-month-old female Sprague-Dawley rats were divided into three equal groups (10 rats in each group): control group (with sham operation, treated with drug vehicle); OVX/T1DM group (ovariectomized diabetic rats); OVX/T1DM-SAL group, comprising ovariectomized diabetic rats treated with salidroside (20 mg/kg body weight) by gavage. The results showed that after 60 consecutive days of treatment, the bone mineral density (BMD) of OVX/T1DM-SAL increased significantly compared with the OVX/T1DM group (p < 0.01). The level of serum bone turnover markers, including alkaline phosphatase (ALP), cross linked c-telopeptide of type I collagen (CTX-1), osteocalcin, N-terminal propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase 5b (TRACP 5b) were all increased in the OVX/T1DM group compared with the control (p < 0.01), and those were decreased by salidroside treatment. Meanwhile, the bone histopathological changes were also attenuated, and the bone marrow adipogenesis was inhibited in salidroside treated rats. Moreover, protein and mRNA ratio of bone osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) was upregulated in ovariectomized diabetic rats by salidroside treatment. The results above indicated that the protective effect of salidroside on bone loss induced by ovariectomy and diabetes was mainly due to its ability to suppress bone turnover, inhibit bone marrow adipogenesis, and up-regulate the OPG/RANKL ratio.
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spelling doaj.art-79953eaff0d54b5c8caa3d18e0775b292022-12-21T16:58:29ZengMDPI AGMolecules1420-30492018-09-01239239810.3390/molecules23092398molecules23092398Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL RatioHongxing Zheng0Shanshan Qi1Chen Chen2Chinese-German Joint Laboratory for Natural Product Research, College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, Shaanxi, ChinaVitamin D Research Institute, Qinling-Bashan Mountains Bioresources Comprehensive Department C.I.C, Shaanxi University of Technology, Hanzhong 723000, Shaanxi, ChinaChinese-German Joint Laboratory for Natural Product Research, College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, Shaanxi, ChinaPostmenopausal diabetic women have a high risk of fractures. Salidroside has preventive effects on estrogen deficiency-induced osteoporosis and has hypoglycemic effects on diabetes in rats. However, whether salidroside inhibits bone loss in postmenopausal diabetic patients is still unknown. Here, we established a rat model of osteoporosis to investigate the protective effects of salidroside on bone loss induced by ovariectomy combined with diabetes, also investigating the underlying mechanisms. Two-month-old female Sprague-Dawley rats were divided into three equal groups (10 rats in each group): control group (with sham operation, treated with drug vehicle); OVX/T1DM group (ovariectomized diabetic rats); OVX/T1DM-SAL group, comprising ovariectomized diabetic rats treated with salidroside (20 mg/kg body weight) by gavage. The results showed that after 60 consecutive days of treatment, the bone mineral density (BMD) of OVX/T1DM-SAL increased significantly compared with the OVX/T1DM group (p < 0.01). The level of serum bone turnover markers, including alkaline phosphatase (ALP), cross linked c-telopeptide of type I collagen (CTX-1), osteocalcin, N-terminal propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase 5b (TRACP 5b) were all increased in the OVX/T1DM group compared with the control (p < 0.01), and those were decreased by salidroside treatment. Meanwhile, the bone histopathological changes were also attenuated, and the bone marrow adipogenesis was inhibited in salidroside treated rats. Moreover, protein and mRNA ratio of bone osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) was upregulated in ovariectomized diabetic rats by salidroside treatment. The results above indicated that the protective effect of salidroside on bone loss induced by ovariectomy and diabetes was mainly due to its ability to suppress bone turnover, inhibit bone marrow adipogenesis, and up-regulate the OPG/RANKL ratio.http://www.mdpi.com/1420-3049/23/9/2398salidrosideboneosteoporosisdiabetesOPGRANKLbone turnover markers
spellingShingle Hongxing Zheng
Shanshan Qi
Chen Chen
Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio
Molecules
salidroside
bone
osteoporosis
diabetes
OPG
RANKL
bone turnover markers
title Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio
title_full Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio
title_fullStr Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio
title_full_unstemmed Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio
title_short Salidroside Improves Bone Histomorphology and Prevents Bone Loss in Ovariectomized Diabetic Rats by Upregulating the OPG/RANKL Ratio
title_sort salidroside improves bone histomorphology and prevents bone loss in ovariectomized diabetic rats by upregulating the opg rankl ratio
topic salidroside
bone
osteoporosis
diabetes
OPG
RANKL
bone turnover markers
url http://www.mdpi.com/1420-3049/23/9/2398
work_keys_str_mv AT hongxingzheng salidrosideimprovesbonehistomorphologyandpreventsbonelossinovariectomizeddiabeticratsbyupregulatingtheopgranklratio
AT shanshanqi salidrosideimprovesbonehistomorphologyandpreventsbonelossinovariectomizeddiabeticratsbyupregulatingtheopgranklratio
AT chenchen salidrosideimprovesbonehistomorphologyandpreventsbonelossinovariectomizeddiabeticratsbyupregulatingtheopgranklratio