Chlorogenic Acid Prevents Osteoporosis by Shp2/PI3K/Akt Pathway in Ovariectomized Rats

Autor: Si Jian Lin, Shi Yao Wen, Jiang Hua Dai, Fen Fen Yao, Yi Cheng Zhou, Rong Ping Zhou, Wen Bing Wan, Hui Bing Ruan, Jun Luo, Jin Xu, Hui Ling Zuo, Mei Lan Zhu, Wei Song
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Critical Care and Emergency Medicine
Physiology
Osteoporosis
lcsh:Medicine
Protein Tyrosine Phosphatase
Non-Receptor Type 11
Biochemistry
Bone remodeling
Rats
Sprague-Dawley
Phosphatidylinositol 3-Kinases
RNA interference
0302 clinical medicine
Bone Density
Osteogenesis
Medicine and Health Sciences
Cyclin D1
Femur
Cell Cycle and Cell Division
RNA
Small Interfering
Connective Tissue Diseases
lcsh:Science
Musculoskeletal System
Trauma Medicine
Cells
Cultured
Osteoporosis
Postmenopausal
Phosphoinositide-3 Kinase Inhibitors
Bone mineral
Multidisciplinary
Chemistry
Cell Differentiation
Osteoblast
Osteoblast Differentiation
Nucleic acids
medicine.anatomical_structure
Genetic interference
Cell Processes
Bone Fracture
030220 oncology & carcinogenesis
Ovariectomized rat
Alkaline phosphatase
Epigenetics
Female
Bone Remodeling
Anatomy
Chlorogenic Acid
Traumatic Injury
Research Article
medicine.medical_specialty
endocrine system
Morpholines
Ovariectomy
03 medical and health sciences
Rheumatology
Cyclins
Internal medicine
Genetics
medicine
Animals
Humans
Protein kinase B
Skeleton
PI3K/AKT/mTOR pathway
Cell Proliferation
Osteoblasts
lcsh:R
Biology and Life Sciences
Estrogens
Mesenchymal Stem Cells
Cell Biology
medicine.disease
Hormones
Rats
030104 developmental biology
Endocrinology
Chromones
RNA
lcsh:Q
Gene expression
Physiological Processes
Proto-Oncogene Proteins c-akt
Developmental Biology
Zdroj: PLoS ONE, Vol 11, Iss 12, p e0166751 (2016)
PLoS ONE
ISSN: 1932-6203
Popis: 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, 17α-ethinylestradiol (E2), or CGA at 9, 27, or 45 mg/kg/d. The rats’ femoral metaphyses were evaluated by micro-computed tomography (μCT). 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 μM enhanced BMSC proliferation in a dose-dependent manner. CGA at 0.1 to 10 μM increased phosphorylated Akt (p-Akt) and cyclin D1. These effects were reversed by LY294002. CGA at 1 or 10 μM 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.
Databáze: OpenAIRE
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