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Anagliptin stimulates osteoblastic cell differentiation and mineralization.

阿格列汀刺激成骨细胞分化和矿化。

  • 影响因子:3.78
  • DOI:10.1016/j.biopha.2019.109796
  • 作者列表:"Dong C","Yang H","Wang Y","Yan X","Li D","Cao Z","Ning Y","Zhang C
  • 发表时间:2020-06-16
Abstract

:Osteoporosis is a common debilitating bone disease characterized by loss of bone mass and degradation of the bone architecture, which is primarily driven by dysregulated differentiation of mesenchymal stem cells into bone-producing osteoblasts. Osteoblasts contribute to bone formation by secreting various proteins that guide the deposition of bone extracellular matrix, such as alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). The Wnt/β-catenin pathway is widely recognized as a regulator of bone mass and is required to maintain bone homeostasis. Hormones have long been recognized as playing a key role in bone metabolism, and in recent years, growing evidence has shown that diabetes is a risk factor for osteoporosis. In the present study, we investigated the effects of the antidiabetic drug anagliptin on the differentiation and mineralization of osteoblasts induced by osteogenic medium. Anagliptin promotes insulin production via inhibition of dipeptidyl peptidase IV (DPP-4), an enzyme that targets the incretin hormone glucagon-like peptide 1 (GLP-1) for degradation. Our findings show that anagliptin significantly increases the differentiation of MSCs into osteoblasts via activation of RUNX2. Anagliptin significantly increased matrix deposition and mineralization by osteoblasts, as evidenced by elevated levels of ALP, OCN, OPN, and BMP-2. We further demonstrate that anagliptin activates the canonical and noncannonical Wnt signaling pathways and that silencing of Wnt/β-catenin signaling completely abolished the effects of anagliptin. Thus, anagliptin might be a safe, effective therapy for type II diabetes that might show promise as a therapy against osteoporosis.

摘要

: 骨质疏松症是一种常见的衰弱性骨病,以骨量丢失和骨结构退化为特征,主要是由间充质干细胞向骨生成成骨细胞分化失调驱动的。成骨细胞通过分泌多种引导骨细胞外基质沉积的蛋白,如碱性磷酸酶 (ALP) 、骨钙素 (OCN) 和骨桥蛋白 (OPN),促进骨形成。Wnt/β-catenin 通路被广泛认为是骨量的调节因子,是维持骨稳态所必需的。长期以来,激素被认为在骨代谢中起着关键作用,近年来,越来越多的证据表明糖尿病是骨质疏松症的危险因素。在本研究中,我们研究了抗糖尿病药物 anagliptin 对成骨培养基诱导的成骨细胞分化和矿化的影响。Anagliptin 通过抑制二肽基肽酶 IV (DPP-4) 促进胰岛素生成,后者是一种靶向肠促胰岛素激素胰高血糖素样肽 1 (GLP-1) 降解的酶。我们的研究结果表明,anagliptin 通过激活 runx2 显著增加 MSCs 向成骨细胞的分化。Anagliptin 可显著增加成骨细胞的基质沉积和矿化,表现为 ALP 、 OCN 、 OPN 和 BMP-2 水平升高。我们进一步证明 anagliptin 激活经典和非经典 Wnt 信号通路,Wnt/β-catenin 信号通路的沉默完全消除了 anagliptin 的作用。因此,anagliptin 可能是一种安全、有效的 II 型糖尿病治疗方法,有望成为抗骨质疏松症的治疗方法。

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影响因子:3.59
发表时间:2020-01-29
来源期刊:Food & function
DOI:10.1039/c9fo01817d
作者列表:["Galán MG","Weisstaub A","Zuleta A","Drago SR"]

METHODS::Apparent calcium absorption, total bone mineral content and density, and mineral contents of the right femur were studied using a growing rat model. Twenty-four male Wistar rats were fed with diets based on extruded whole grain red (RSD) or white sorghum (WSD), and control diet (CD) up to 60 days. The animals fed with sorghum diets consumed less and gained less weight compared to those fed with CD, but the efficiency of all diets was similar. Calcium intake was lower in animals fed with sorghum diets, related to the lower total intake of these animals. Apparent calcium absorption in animals fed with RSD was lower than in those fed with CD (CD: 72.7%, RSD: 51.0%, WSD: 64.8%). No significant differences in bone mineral density of total body, spin, femur, distal femur, tibia and proximal tibia were observed among the groups. However, Ca and P contents in the right femur of the rats consuming RSD were lower, indicating a certain imbalance in the metabolism of these minerals.

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影响因子:1.50
发表时间:2020-01-24
来源期刊:Skeletal radiology
DOI:10.1007/s00256-020-03378-z
作者列表:["Schaffler-Schaden D","Kneidinger C","Schweighofer-Zwink G","Flamm M","Iglseder B","Pirich C"]

METHODS:OBJECTIVE:Controversy exists about the impact of bone mineral density (BMD) and fracture risk in newly diagnosed patients with breast cancer (BC). It is presumed that there are differences in BMD between women with BC and healthy controls. BMD is therefore considered as a potential marker to predict BC risk. This study was conducted to investigate the association of BMD, trabecular bone score (TBS) and fracture risk in younger postmenopausal women with hormone responsive BC. METHODS:Overall, 343 women were examined. Women with BC were matched to a control group of the general population. Forty-nine women and fifty-nine controls were included in the final analysis. All subjects underwent dual energy x-ray absorptiometry (DXA) of the lumbar spine, femoral neck, and the total hip to evaluate bone mineral density. The 10-year fracture risk for a major osteoporotic fracture was assessed using the FRAX-score and the TBS-adjusted FRAX-Score, respectively. RESULTS:Lumbar and femoral neck BMD were similar in BC patients and controls. No difference was found for TBS of the spine (1.38 ± 0.1 vs.1.36 ± 0.09) in the BC and the control group, respectively (p = 0.19). The 10- year probability for a major osteoporotic fracture (MoF) or femoral neck (FN) fracture was 6.1 (± 2.6%) and 0.9 (± 1.2%) in the BC group vs. 6.7 (± 3.5%) (p = 0.33) and 0.9 (± 1.1%) (p = 0.73) in the control group. CONCLUSION:Postmenopausal women younger than 60 years with breast cancer do not show any differences in baseline BMD, TBS, or TBS adjusted FRAX in comparison to controls.

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影响因子:5.97
发表时间:2020-01-27
DOI:10.1002/adhm.201901385
作者列表:["Gurumurthy B","Tucci MA","Fan LW","Benghuzzi HA","Pal P","Bidwell GL","Salazar Marocho SM","Cason Z","Gordy D","Janorkar AV"]

METHODS::The goals of this study are to evaluate the ability of the multicomponent collagen-elastin-like polypeptide (ELP)-Bioglass scaffolds to support osteogenesis of rat mesenchymal stem cells (rMSCs), demonstrate in vivo biocompatibility by subcutaneous implantation in Sprague-Dawley rats, monitor degradation noninvasively, and finally assess the scaffold's ability in healing critical-sized cranial bone defects. The collagen-ELP-Bioglass scaffold supports the in vitro osteogenic differentiation of rMSCs over a 3 week culture period. The cellular (rMSC-containing) or acellular scaffolds implanted in the subcutaneous pockets of rats do not cause any local or systemic toxic effects or tumors. The real-time monitoring of the fluorescently labeled scaffolds by IVIS reveals that the scaffolds remain at the site of implantation for up to three weeks, during which they degrade gradually. Micro-CT analysis shows that the bilateral cranial critical-sized defects created in rats lead to greater bone regeneration when filled with cellular scaffolds. Bone mineral density and bone microarchitectural parameters are comparable among different scaffold groups, but the histological analysis reveals increased formation of high-quality mature bone in the cellular group, while the acellular group has immature bone and organized connective tissue. These results suggest that the rMSC-seeded collagen-ELP-Bioglass composite scaffolds can aid in better bone healing process.

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