Astragalus Polysaccharide Injection Ameliorates the Apoptosis of Chondrocytes in the Ovariectomized Osteoporosis Mouse Model via Modulating Protein Kinase B/Glycogen Synthase Kinase 3 Beta Signal Transduction

The Akt/GSK3 signal pathway exerts an impact on the apoptosis of chondrocytes. We planned to elucidate the role and mechanism of Akt/GSK3 signal transduction in ovariectomized osteoporosis. 50 female mice in SPF-graded and healthy condition were processed to establish the ovariectomized osteoporosis model, while 12 of the healthy mice were set as blank controls. The successfully established ovariectomized osteoporosis models were divided into model group (12 mice) and Astragalus group (12 mice). The following measurements were conducted: the bone mineral density in the left humerus, serum estrogen level and Cx43 protein level in osteoblasts, proportion of apoptotic cells, as well as the protein and mRNA levels of Akt and GSK3β in murine bone tissues via Western blotting and RT-PCR detection, respectively. The bone mineral density of mice in Astragalus group was the highest (0.174±0.04) g/cm2. The positive rate of Cx43 protein expression, apoptosis rate, as well as the protein and mRNA levels of Akt in osteocytes were significantly decreased (P < 0.05), but still significantly higher than model group. Estrogen level in Astragalus group was (87.52 ±8.69) pmol/L. The positive rate of Cx43 expression, apoptosis rate, as well as the protein and mRNA levels of GSK3β in osteocytes were decreased in comparison to model group (P < 0.05). Astragalus polysaccharide injection could ameliorate the apoptosis of chondrocytes and downregulate Cx43 protein via modulating Akt/GSK3β signal transduction, thereby exerting a therapeutic effect on ovariectomized osteoporosis.

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A REVIEW: MECHANISTIC INSIGHTS INTO THE EFFECT OF THYROID DISORDERS ON ESTROGEN LEVEL AND BONE MINERAL DENSITY

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2019v11i10.34447 ◽

2019 ◽

pp. 9-17

Author(s):

MINAKSHI JOSHI ◽

SHRADHA BISHT ◽

MAMTA F. SINGH

Keyword(s):

Bone Mineral Density ◽

Thyroid Hormone ◽

Bone Turnover ◽

Bone Mineral ◽

Thyroid Stimulating Hormone ◽

Thyroid Disorders ◽

Hypothyroid Patient ◽

Mineral Density ◽

Estrogen Level ◽

The Impact

Thyroid hormone serves as an indispensable component for the optimum functioning of various biological systems. They curb body’s metabolism, regulates the estrogen level, regulates bone turnover, essential for skeletal development and mineralization. Within the scope of knowledge, it is intimately familiar that thyroid disorders have widespread systemic manifestations, among which in hypothyroidism, even though elevated TSH (thyroid-stimulating hormone) may reduce estrogen level which in turn stimulates osteoclasts and thus cause osteoporosis, while hyperthyroidism accelerates bone turnover. Hypothyroidism does not directly interfere with the skeletal integrity, but treatment with levothyroxine for the suppression of TSH to bring the hypothyroid patient to euthyroid state for a long haul; lead to simultaneous reduction in bone mass and in (bone mineral density) BMD. After the initial relevation of the correlation between thyroid disorders and osteoporosis in numerous studies have emphasized that both hypo and hyperthyroidism either directly or indirectly affects the bone mineral density or leads to the progression of osteoporosis. Therefore the present study is aimed and so designed to review all the possible associations between them and the impact of thyroid disorders on estrogen level and bone mineral density. The main findings of this review indicate that both excesses as well as deficiency of thyroid hormone can be potentially deleterious for bone tissue.

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Effects of ginsenoside Rg3 on bone loss, bone mineral density and osteoclast number in glucocorticoid-induced osteoporosis rats, and the likely michanism of action

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i4.19 ◽

2020 ◽

Vol 19 (4) ◽

pp. 811-815

Author(s):

Maoxiu Peng ◽

Gangyl Jiang ◽

Shaoqi He ◽

Chengxuan Tang

Keyword(s):

Bone Mineral Density ◽

Bone Loss ◽

Bone Mineral ◽

Lumbar Vertebrae ◽

Ginsenoside Rg3 ◽

Model Group ◽

Mineral Density ◽

Alendronate Sodium ◽

Trabecular Thickness ◽

Osteoclast Number

Purpose: To investigate the effect of ginsenoside Rg3 on bone loss, bone mineral density (BMD) and osteoclast number in glucocorticoid-induced osteoporosis (GIOP) rats, and the mechanism of action involved.Methods: Sixty female Wistar rats were assigned to control, model group, ginsenoside Rg3, and alendronate sodium groups, comprised of 15 rats per group. The osteoporosis rat model was established via intramuscular injection of dexamethasone. Changes in bone mineral content (BMC), BMD trabecular thickness and area, osteoblasts and osteoclasts in femurs and lumbar vertebrae were measured after 3 months of treatment.Results: There were significantly higher BMC and BMD levels in ginsenoside Rg3 group than in alendronate rats (p < 0.05). The thickness and trabecular area in femur and lumbar vertebrae in the ginsenoside Rg3 group were significantly higher than those in the model group (p < 0.05), but were comparable with those in the alendronate sodium group (p > 0.05). There were marked increases in osteoblasts, and marked decreases in osteoclasts in the ginsenoside Rg3 group, alendronate sodium and control rats, relative to model rats (p < 0.05).Conclusion: Ginsenoside Rg3 arrests bone loss, and enhances bone density, trabecular thickness and area, bone microstructure, osteoblast activity and population of osteoclasts number in glucocorticoidinduced osteoporotic rats. This provides a new research direction for the clinical treatment ofosteoporosis. Keywords: Ginseng soap, Rg3, Glucocorticoid, Osteoporosis, Bone loss, Bone mineral density, Osteoclast population

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Lentivirus-TAZ Administration Alleviates Osteoporotic Phenotypes in the Femoral Neck of Ovariectomized Rats

Cellular Physiology and Biochemistry ◽

10.1159/000438629 ◽

2016 ◽

Vol 38 (1) ◽

pp. 283-294 ◽

Cited By ~ 8

Author(s):

Zhanhai Yin ◽

Yan Zhang ◽

Zheyang Wang ◽

Lin Ding ◽

Ainiwaerjiang Damaolar ◽

...

Keyword(s):

Bone Mineral Density ◽

Femoral Neck ◽

Bone Mineral ◽

Neck Region ◽

Ovariectomized Rats ◽

Type I ◽

Mrna Levels ◽

Mineral Density ◽

Trabecular Thickness ◽

Ovx Rats

Background: Osteoporosis is characterized by impairment of bone mass, strength, and microarchitecture, leading to the susceptibility to fragility fractures, especially in femoral neck region. Transcriptional coactivator with PDZ-binding motif (TAZ) facilitates osteogenesis while suppressing adipogenesis via regulation of transcriptional activities of runt-related transcription factor 2 and peroxisome proliferator-activated receptor γ. Here, we validated the role of TAZ in vivo using an ovariectomized (OVX) rat model of osteoporosis. Methods: Serum alkaline phosphatase, triglyceride, cholesterol and urinary hydroxyproline were measured on an automatic analyzer using diagnostic reagent kits. Serum OCN and C-terminal cross-linked telopeptides of type I collagen were measured using ELISA. Bone mineral density was measured using dual-energy X-ray scanner. Mechanical parameters were detected by three-point bending assays. Bone volume per tissue volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. No), and trabecular separation (Tb. Sp) were measured by MicroCT. The mRNA and protein levels were quantified by Realtime PCR and Western Blotting respectively. Results: After injections of lentivirus overexpressing TAZ into the femoral neck region, bone mineral density, ultimate force, stiffness, BV/TV, Tb. Th, and Tb. No were significantly increased, whereas Tb. Sp was dramatically decreased. In the TAZ-overexpression region in the femoral neck of OVX rats, the mRNA levels of Runx2 and osteocalcin were obviously elevated, whereas that of PPARγ and adipocyte protein 2 were downregulated. Conclusion: Lentivirus-mediated TAZ gene therapy alleviated the osteoporotic phenotypes in the femoral neck of OVX rats, providing an alternative strategy for the treatment of postmenopausal osteoporosis and prevention of osteoporotic fracture.

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Jingui Shenqi Pills Prevents and Treats Postmenopausal Osteoporosis via Regulating the BMP/Smad Signaling Pathway

10.21203/rs.3.rs-669680/v1 ◽

2021 ◽

Author(s):

Qian Zhang ◽

Xu Yang ◽

Ke Ma ◽

Yanan Zhang ◽

Xu Tian ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Treated Group ◽

Sham Operation ◽

Model Group ◽

Mineral Density ◽

Sham Operation Group ◽

Treatment Groups ◽

Calcium Phosphorus ◽

Operation Group

Abstract Background: Jingui Shenqi （JGSQ for short）pills is a traditional Chinese medicine formula, which has the functions of warming and tonifying kidney-yang, generating essence and filling marrow, warming tendons and veins and bones, and improving bone mineral density. The aim of this study was to investigate the effect and mechanism of JGSQ pills in preventing and treating postmenopausal osteoporosis.Methods : Twelve-week-old SPF female SD rats (n=48) were used in this study. Following the ovariectomy operation (n=40), the rats were randomly divided into the model group, (high, medium, and low dose groups) treated with Jingui Shenqi pills and estradiol group. Recorded the weight gain of rats and calculated the uterine coefficient; To detect the expression of serum calcium, phosphorus, ALP and OPG; HE staining was used to detect the pathological changes of femur; In all the groups, Micro-CT was used for detection of bone mineral density and bone microstructure; and gene expression of BMP-2, Smad1, and Runx2 in rat bone tissue was determined by RT-PCR and Western Blot methods.Results: Compared with the sham operation group, rats in the model group had the highest increase in body weight and the lowest uterine coefficient. Each of the treatment groups had a modest increase in weight gain. Micro-CT and HE staining showed a decrease in bone mineral density in the model group with shorter, thinner, broken, and osteoporotic trabeculae of the femur. The bone mineral density in Jingui Shenqi pills treatment groups had a significant increase with an improved bone microstructure and intact bone trabecular as compared to the model group. Serum ALP in the model group was significantly higher than in the sham operation group but the serum calcium, phosphorus and OPG was significantly lower. The Jingui Shenqi pills treatment groups and the estradiol treated group had lower serum ALP and increased serum calcium, phosphorus and OPG.There was decreased gene expression of BMP-2, Smad1, and Runx2 in the bone tissue of the model group compared to the sham operation group. BMP-2, Smad1, and Runx2 gene expression in Jingui Shenqi pills treated group and estradiol treated group was significantly higher than that of the model group.Conclusion: Jingui Shenqi pills improve the microstructure of bone tissue and increase bone mineral density thus resolving osteoporosis. This is achieved by regulating BMP/Smad signaling pathway and increasing the expression of osteogenic factors BMP-2, Smad1, and Runx2.

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