scholarly journals Role of Metformin on Osteoblast Differentiation in Type 2 Diabetes

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Lin Jiating ◽  
Ji Buyun ◽  
Zhang Yinchang
Keyword(s):  
Mineral Metabolism ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Osteoblast Activity ◽  
Extracellular Signal ◽  
Energy Sensor ◽  
Glycation End Products ◽  
Proliferation And Differentiation ◽  
Related Transcription Factor ◽  
Amp Activated Protein Kinase

Metformin, an effective hypoglycemic, can modulate different points of malignant mass, polycystic ovary syndrome (PCOS), cardiovascular diseases, tuberculosis, and nerve regeneration. Recently, the effect of metformin on bone metabolism has been analyzed. Metformin relies on organic cation transporters (OCT1), a polyspecific cell membrane of the solute carrier 22A (SLC22A) gene family, to facilitate its intracellular uptake and action on complex I of the respiratory chain of mitochondria. These changes activate the cellular energy sensor AMP-activated protein kinase (AMPK). Thus, the increased cellular AMP/ATP ratio causes a dramatic and progressive activation of insulin and lysosomes, resulting in a decrease in intracellular glucose level, which promotes osteoblast proliferation and differentiation. AMPK also phosphorylates runt-related transcription factor 2 (Runx2) at S118, the lineage-specific transcriptional regulators, to promote osteogenesis. Metformin phosphorylates extracellular signal-regulated kinase (ERK), stimulates endothelial and inducible nitric oxide synthases (e/iNOS), inhibits the GSK3β/Wnt/β-catenin pathway, and promotes osteogenic differentiation of osteoblasts. The effect of metformin on hyperglycemia decreases intracellular reactive oxygen species (ROS) and advanced glycation end-products (AGEs) in collagen, and reduced serum levels of insulin-like growth factors (IGF-1) were beneficial for bone formation. Metformin has a certain effect on microangiopathy and anti-inflammation, which can induce osteoporosis, activate the activity of osteoclasts, and inhibit osteoblast activity, and has demonstrated extensive alteration in bone and mineral metabolism. The aim of this review was to elucidate the mechanisms of metformin on osteoblasts in insulin-deficient diabetes.

Upregulation of signal transducer and activator of transcription 4 promotes osteoblast activity by activating AMP-activated protein kinase based on cationic liposome transfection

2020 ◽  
Vol 10 (11) ◽  
pp. 1836-1845
Author(s):  
Tao Jiang ◽  
Qingzhen Chen ◽  
Min Shao ◽  
Zhen Shen ◽  
Gang Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Osteogenic Differentiation ◽  
Transcriptional Activity ◽  
Cationic Liposome ◽  
Promoter Sequence ◽  
Fluorescence Quantitative Pcr ◽  
Osteoblast Activity ◽  
Activity Factor ◽  
Proliferation And Differentiation ◽  
Amp Activated Protein Kinase

Activation of Protein Kinase AMP-Activated Catalytic Subunit Alpha (AMPKα) is an important regulatory pathway for osteogenic differentiation. STAT4 acts as a transcriptional activity factor to regulate the transcription of many genes and is potentially a regulatory factor for AMPKα transcription activity. To confirm the regulatory effect of STAT4 on AMPKα and the effect of STAT4 on osteogenic differentiation, the promoter sequence of AMPKα was analyzed via bioinformatics, the STAT4 overexpression vector was constructed and transfected into human osteoblast-like cells MG-63 by cationic liposome, fluorescence quantitative PCR (RT-qPCR) and western blotting technologies were used to detect the effect of STAT4 on the expression of AMPKα. MTT and ALP activity assays were also used to verify the effect of STAT4 on the proliferation and maturation of osteoblasts by regulating AMPKα expression. Our results showed that STAT4 was a co-transcriptional regulator of AMPKα1 and AMPKα2, which combined the enrichment region of CpG on the promoter sequence of AMPKα1/2. Overexpression of STAT4 significantly increased the expression of AMPKα1 and AMPKα2, which promoted the proliferation and maturation of osteoblasts. We concluded that STAT4 was a transcriptional activator of AMPKα and promoting STAT4 expression enhances the proliferation and differentiation activity of AMPKα in osteoblasts.

scholarly journals Effects of Huanglian Jiedu Decoration in Rat Gingivitis

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Fangbo Zhang ◽  
Ya Geng ◽  
Haiyu Zhao ◽  
Hongjie Wang ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Serum Levels ◽  
Gingival Tissue ◽  
Protective Effects ◽  
Histological Changes ◽  
Tissue Samples ◽  
Extracellular Signal ◽  
Cytokine Levels ◽  
Total Antioxidant ◽  
Amp Activated Protein Kinase ◽  
Inflammation Reaction

Gingivitis is an inflammatory disease that affects gingival tissues through a microbe-immune interaction. Huanglian Jiedu decoction (HLJD) is used traditionally for clearing and detoxifying in China, which had been reported to possess many pharmacological effects. Rat gingival inflammation model was established by lipopolysaccharide (LPS) injection for 3 consecutive days, and HLJD was given by gavage before LPS injection. After 3 days rats were sacrificed and tissue samples were evaluated. Serum cytokine levels such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunoabsorbent assay (ELISA). Oxidative stress related molecules such as total antioxidant capacity (T-AOC), malondialdehyde (MDA), and reactive oxygen species (ROS) were determined. Expression of AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway were inspected by western blotting. Histological changes of gingival tissues were tested with hematoxylin-eosin (HE) staining. HLJD significantly decreased serum levels of IL-6 and TNF-α, suppressed generation of MDA and ROS, and enhanced T-AOC creation. Moreover, HLJD inhibited expressions of AMPK and ERK1/2. The inflammation severity of gingival tissue by HE staining was severe in model group but relieved in HLJD group obviously. HLJD exhibited protective effects against gingival damage through suppressing inflammation reaction and elevating antioxidation power.

Effect of long-term orlistat treatment on serum levels of advanced glycation end-products in women with polycystic ovary syndrome

2006 ◽  
Vol 0 (0) ◽  
pp. 061031010617005-??? ◽  
Author(s):  
Evanthia Diamanti-Kandarakis ◽  
Ilias Katsikis ◽  
Christina Piperi ◽  
Krystallenia Alexandraki ◽  
Dimitrios Panidis
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Advanced Glycation End Products ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Advanced Glycation ◽  
Ovary Syndrome ◽  
Glycation End Products ◽  
End Products

scholarly journals Physical Performance Regarding Handgrip Strength in Women with Polycystic Ovary Syndrome

2020 ◽  
Vol 42 (12) ◽  
pp. 811-819
Author(s):  
Gislaine Satyko Kogure ◽  
Victor Barbosa Ribeiro ◽  
Flávia Ganoa de Oliveira Gennaro ◽  
Rui Alberto Ferriani ◽  
Cristiana Libardi Miranda-Furtado ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Physical Performance ◽  
Lean Mass ◽  
Polycystic Ovary ◽  
Handgrip Strength ◽  
Serum Levels ◽  
Total Testosterone ◽  
Dominant Hand ◽  
Ovary Syndrome ◽  
Pcos Group

Abstract Objective The present study aimed to investigate the physical performance of handgrip strength (HGS) in women with polycystic ovary syndrome (PCOS). Methods A case-control study that included 70 women with PCOS and 93 age-matched healthy women aged between 18 and 47 years with body mass index (BMI) between 18 Kg/m2–39.9 Kg/m2. The serum levels of total testosterone, androstenedione, insulin, estradiol, thyroid-stimulating hormone (TSH), prolactin, sex hormone-binding globulin (SHBG), and 17-hydroxyprogesterone (17-OHP) were measured. The free androgen index (FAI) and the homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. The body composition regions of interest (ROIs) were assessed by dual-energy X-ray absorptiometry (DXA), and the handgrip strength (HGS) was evaluated for both the dominant and the non-dominant hands with a manual Sammons Preston (Bolingbrook, IL, US) bulb dynamometer. Results Women with PCOS had high serum levels of total testosterone (p < 0.01), androstenedione (p = 0.03), and insulin (p < 0.01), as well as high FAI (p < 0.01) and HOMA-IR (p = 0.01) scores. Compared with the non-PCOS group, the PCOS group had greater total lean mass in the dominant hand (p < 0.03) and greater HGS in both the dominant and the non-dominant hands (p < 0.01). The HGS was correlated with lean mass (p < 0.01). Conclusion Women with PCOS have greater HGS. This may be associated with age and BMI, and it may be related to lean mass. In addition, the dominance effect on muscle mass may influence the physical performance regarding HGS in women with PCOS.

C1QTNF6 participates in the pathogenesis of PCOS by affecting the inflammatory response of granulosa cells

2021 ◽  
Author(s):  
Sisi Yan ◽  
Jinli Ding ◽  
Yi Zhang ◽  
Jiayu Wang ◽  
Sainan Zhang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mouse Models ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Low Grade ◽  
Reactive Protein ◽  
Reproductive Endocrine ◽  
Factor Α

Abstract Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease. It has been reported that chronic low-grade inflammation might participate in its pathogenesis. C1q and TNF related 6 (C1QTNF6) is a newly identified adiponectin paralog associated with inflammation. The aim of the present study was to investigate the role of C1QTNF6 in the development of chronic inflammation in PCOS and the underlying molecular mechanism. After analyzing the expression of C1QTNF6 in the serum and granulosa cells (GCs) of PCOS patients and healthy controls, we verified the roles of C1QTNF6 in inflammation through dehydroepiandrosterone-induced PCOS mouse models and cell models of lipopolysaccharide (LPS)-induced inflammation. The results demonstrated that C1QTNF6 expression in the serum and GCs of patients with PCOS was significantly elevated compared with those of the controls, and similar results were observed in the serum and ovary of PCOS mouse models. In PCOS mice and C1QTNF6-overexpressing PCOS mice, serum levels of pro-inflammatory factors including C-reactive protein (CRP), interleukin 6 (IL6) and tumor necrosis factor-α (TNFα) were increased, while the opposite effects were observed when C1QTNF6 was downregulated in PCOS mice. Furthermore, C1QTNF6 overexpression upregulated the levels of TNFα, IL6, and CRP and activated the AKT/NF-κB pathway in LPS-treated KGN cells, whereas C1QTNF6 knockdown and BAY-117082 (an NF-κB inhibitor) treatment resulted in the opposite effects. Taken together, our results indicate that C1QTNF6 is involved in the pathogenesis of PCOS by affecting the inflammatory response via the AKT/NF-κB signaling pathway.

scholarly journals Synergistic attenuation of ovariectomy-induced bone loss by combined use of fish oil and 17β-oestradiol

2017 ◽  
Vol 117 (4) ◽  
pp. 479-489 ◽  
Author(s):  
Youri Jin ◽  
Myoungsook Lee ◽  
Yongsoon Park
Keyword(s):  
Transcription Factor ◽  
Bone Loss ◽  
Protective Efficacy ◽  
Recovery Period ◽  
Serum Levels ◽  
Protective Mechanism ◽  
Beneficial Effects ◽  
Combined Use ◽  
Related Transcription Factor ◽  
Turnover Markers

AbstractOestrogen and n-3 PUFA, especially EPA and DHA, have been reported to have beneficial effects on bone loss. Thus, the purpose of the present study was to investigate the synergistic bone-protective mechanism of combined treatments of EPA+DHA supplementation and oestrogen injection in ovariectomised rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0 %, 1 % or 2 % n-3 PUFA (EPA+DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and after a 1-week recovery period rats were injected with either 17β-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Combined use of n-3 PUFA and E2 synergistically increased femoral cortical bone volume, bone mineral content and the bone expression of runt-related transcription factor 2 (RUNX2), but decreased the bone expression of IL-1β. Both n-3 PUFA and E2 decreased the bone expressions of IL-7, TNF-α and PPAR-γ, and increased the bone expression of oestrogen receptor-α. n-3 PUFA in the presence of E2 and E2 alone significantly decreased the bone expressions of IL-1β and IL-6 and increased the bone expression of RUNX2. E2 significantly decreased the serum levels of bone turnover markers and the bone expression of receptor activator of NF-κB ligand, but decreased the bone expression of osteoprotegerin. The combined use of n-3 PUFA and E2 exerted synergistic bone-protective efficacy through up-regulation of RUNX2, an essential transcription factor for bone formation, as well as the suppression of bone-resorbing cytokine IL-1β.

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