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OPG AND beta cell proliferation

Kazuyuki Yusa, Osamu Yamamoto, Mitsuyoshi Iino, Hiroshi Takano, Masayuki Fukuda, Zhiwei Qiao, Toshihiro Sugiyama
OBJECTIVE: Zinc is an essential element for proliferation, differentiation and survival in various cell types. In a previous study, we found that zinc ions released from zinc-modified titanium surfaces (eluted zinc ions; EZ) stimulate cell viability, osteoblast marker gene expression and calcium deposition in human bone marrow-derived mesenchymal cells (hBMCs). The aim of the present study was to investigate the effects of EZ on osteoblast differentiation among dental pulp stem cells (DPSCs) in vitro...
November 2016: Archives of Oral Biology
Emanuela Mrak, Lavinia Casati, Francesca Pagani, Alessandro Rubinacci, Guido Zarattini, Valeria Sibilia
Ghrelin, by binding growth hormone secretagogue receptor (GHS-R), promotes osteoblast proliferation but the signaling mechanism of GHS-R on these cells remains unclear. Since canonical Wnt/β-catenin pathway is critically associated with bone homeostasis, we investigated its involvement in mediating ghrelin effects in osteoblasts and in osteoblast-osteoclast cross talk. Ghrelin (10(-10)M) significantly increased β-catenin levels in rat osteoblasts (rOB). This stimulatory action on β-catenin involves a specific interaction with GHS-R1a, as it is prevented by the selective GHS-R1a antagonist, D-Lys(3)-GHRP-6 (10(-7)M)...
2015: International Journal of Endocrinology
Yue Wang, Cheng Yang, Wen Li Xie, Yan Wei Zhao, Zong Min Li, Wei Jia Sun, Ling Zhi Li
Puerarin, a daidzein-8-C-glucoside, is the major isoflavone glycoside found in the Chinese herb radix of Pueraria lobata (Willd.) Ohwi, and has received increasing attention because of its possible role in the prevention of osteoporosis. In our previous studies, puerarin reduced the bone resorption of osteoclasts and promoted long bone growth in fetal mouse in vitro. Further study confirmed that puerarin stimulated proliferation and differentiation of osteoblasts in rat. However, the mechanisms underlying its actions on human bone cells have remained largely unknown...
July 2014: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Zilan Lv, Chuan Wang, Taixian Yuan, Yuehong Liu, Tao Song, Yueliang Liu, Chu Chen, Min Yang, Zuchuan Tang, Qiong Shi, Yaguang Weng
Bone morphogenetic protein 9 (BMP9) is a member of the transforming growth factor-β (TGF-β) family, which has been shown to regulate the progression of several tumors. Recent studies indicated that BMP9 affects osteosarcoma (OS) processes, but its specific roles and molecular mechanisms have yet to be fully elucidated. The human OS cell lines 143B and MG63 were used for the present study. We found that BMP9 overexpression suppressed the growth of OS cells, whereas inhibition of BMP9 reversed this effect. Our results also showed that BMP9 overexpression induced G0/G1 phase arrest and apoptosis in OS cells...
February 2014: Oncology Reports
Meimei Liu, Yan Li, Shang-Tian Yang
Curculigoside, a phenolic glycoside, is the main active compound of Curculigo orchioides (Amaryllidaceae, rhizome). C. orchioides is a traditional Chinese herbal medicine and has been commonly used to treat orthopedic disorders and bone healing in Asia. This study evaluated the effect of curculigoside on osteogenic differentiation of human amniotic fluid-derived stem cells (hAFSCs). The results showed that curculigoside stimulated alkaline phosphatase activity and calcium deposition of hAFSCs during osteogenic differentiation in a dose-dependent manner (1-100 μg/mL), while the effects were reduced at the higher concentration of 200 μg/mL...
January 15, 2014: Stem Cells and Development
Y-D Wang, M-F Tao, L Wang, W-W Cheng, X-P Wan
The aim of the work was to investigate the differential regulation by dehydroepiandrosterone (DHEA) of the osteoblastic production via the estrogen receptor beta (ER β)-mediated signaling pathway. Having developed hMG63-ER β cells and hMG63-shER β cells, we analyzed the regulation by DHEA of human osteoblastic viability, the receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), and the differential expression of ER β, ER α, or p-ERK1/2 (extracellular signal-regulated kinase) in hMG63, hMG63-shER β, and hMG63-ER β cells pretreated with or without U0126, flutamide, and ICI 182780, followed by DHEA culture...
June 2012: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Yue Wang, Ling Zhi Li, Yong Liang Zhang, Ya Qin Zhu, Jian Wu, Wei Jia Sun
Estrogen analogues are promising drugs for postmenopausal osteoporosis, but because of their possible side effects such as increased risk of cancer, estrogens which exert their estrogenic effects selectively on bone are desired. It has been shown that rhein inhibits osteoclast formation and bone resorption activity and has an antitumor role in several types of cancers. Having found that rhein had high affinity for the bone mineral, we synthesized estrone-rhein hybrid compounds and confirmed that one of these hybrid compounds, LC, exhibited a selective profile in the bone and prevented bone loss but had no effect on endometrium growth in ovariectomized rats...
April 30, 2011: Molecular and Cellular Endocrinology
Jonathan Green, Philippe Clézardin
Bisphosphonates are widely used to preserve and improve bone health in patients with cancer. Emerging evidence suggests that in addition to their effects on bone health, bisphosphonates may have anticancer activity. Some of the activity associated with bisphosphonates is observed in non-osteoclast cells; therefore, the bioavailability of bisphosphonates is briefly discussed. Structure-function correlations and the molecular and cellular mechanisms that underlie bisphosphonate activity are also examined. In addition to a detailed discussion of the molecular interaction between nitrogen-containing bisphosphonates and farnesyl pyrophosphate synthase and the formation of cytotoxic triphosphoric acid 1-adenosin-5'-yl ester 3-(3-methylbut-3-enyl) ester (ApppI), the effects of bisphosphonates on the transforming growth factor-beta (TGF)-beta pathway, the receptor activator of nuclear factor-kappaB (NFkappaB) ligand (RANKL)/osteoprotegerin (OPG) axis, and novel molecular targets are reviewed...
June 2010: Seminars in Oncology
Jieun Son, Jong-Ho Lee, Ha-Neui Kim, Hyunil Ha, Zang Hee Lee
cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cells and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-beta...
July 23, 2010: Biochemical and Biophysical Research Communications
Hichame Id Boufker, Laurence Lagneaux, Mehdi Najar, Martine Piccart, Ghanem Ghanem, Jean-Jacques Body, Fabrice Journé
BACKGROUND: The proto-oncogene Src is an important non-receptor protein tyrosine kinase involved in signaling pathways that control cell adhesion, growth, migration and differentiation. It negatively regulates osteoblast activity, and, as such, its inhibition is a potential means to prevent bone loss. Dasatinib is a new dual Src/Bcr-Abl tyrosine kinase inhibitor initially developed for the treatment of chronic myeloid leukemia. It has also shown promising results in preclinical studies in various solid tumors...
2010: BMC Cancer
Yi-Chen Lo, Yu-Han Chang, Bai-Lu Wei, Yu-Ling Huang, Wen-Fei Chiou
In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone formation. Here, we examined the effects of betulinic acid on cell proliferation, differentiation, and mineralization of MC3T3-E1 osteoblasts. Then, the impact of betulinic acid on signaling pathways known to be implicated in osteoblastogenesis was explored. Betulinic acid (1-20 microM) markedly increased alkaline phosphatase (ALP) activity and calcium nodule formation, although without a notable effect on cell proliferation...
June 9, 2010: Journal of Agricultural and Food Chemistry
Lin Wang, Shan-ying Peng, Yang Liu, Ping Li, Wen-jie Wang
AIM: To study the effects and mechanism of aromatic aminoketone (SY0916) on bone destruction in vitro. METHODS: MC3T3-E1 cells and bone marrow cells were co-cultured to obtain purified osteoclasts. The proliferation of osteoclast-like cells (OCLs) was determined by MTT assay. The number of osteoclasts was measured by tartrate-resistant acid phosphatase (TRAP) staining. The functioning of osteoclasts was determined by measuring the area of bone resorption pits on bone slices...
April 2010: Acta Pharmacologica Sinica
Ulf Krause, Sean Harris, Angela Green, Joni Ylostalo, Suzanne Zeitouni, Narae Lee, Carl A Gregory
Human mesenchymal stem cells (hMSCs) from bone marrow are regarded as putative osteoblast progenitors in vivo and differentiate into osteoblasts in vitro. Positive signaling by the canonical wingless (Wnt) pathway is critical for the differentiation of MSCs into osteoblasts. In contrast, activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma)-mediated pathway results in adipogenesis. We therefore compared the effect of glycogen-synthetase-kinase-3beta (GSK3beta) inhibitors and PPARgamma inhibitors on osteogenesis by hMSCs...
March 2, 2010: Proceedings of the National Academy of Sciences of the United States of America
Sao-Keng Mok, Wen-Fang Chen, Wan-Ping Lai, Ping-Chung Leung, Xin-Luan Wang, Xin-Sheng Yao, Man-Sau Wong
BACKGROUND AND PURPOSE: Icariin may be the active ingredient in Herba Epimedii, a Chinese herb commonly used for treatment of osteoporosis. The present study aims to delineate the mechanism(s) by which icariin prevents bone loss after ovariectomy (OVX) in vivo and stimulates osteoblastic functions in vitro. EXPERIMENTAL APPROACH: Ovariectomized or sham-operated C57BL/6 mice were treated with vehicle, 17beta-oestradiol or icariin for 6 weeks. Total and trabecular bome mineral density (BMD) as well as polar stress-strain index of distal femur were measured by peripheral computed tomography...
February 2010: British Journal of Pharmacology
H H Huang, T C Brennan, M M Muir, R S Mason
Central (hypothalamic) control of bone mass is proposed to be mediated through beta2-adrenergic receptors (beta2-ARs). While investigations in mouse bone cells suggest that epinephrine enhances both RANKL and OPG mRNA via both beta-ARs and alpha-ARs, whether alpha-ARs are expressed in human bone cells is controversial. The current study investigated the expression of alpha1-AR and beta2-AR mRNA and protein and the functional role of adrenergic stimulation in human osteoblasts (HOBs). Expression of alpha1B- and beta2-ARs was examined by RT-PCR, immunofluorescence microscopy and Western blot (for alpha1B-ARs)...
July 2009: Journal of Cellular Physiology
Mercè Giner, M A José Rios, M A José Montoya, M A Angeles Vázquez, Latifa Naji, Ramón Pérez-Cano
The OPG/RANKL/RANK system is important in the balance between bone formation and resorption. We used primary human osteoblasts (hOBs) cells to examine the impact of 17-beta-estradiol (E2) or/and 1,25-dihydroxyvitamin D (1,25D) in OPG/RANKL system in 28 post-menopausal (PM) women; (a) with hip fracture (OP) or (b) with osteoarthritis (OA). The hOB from OP patients proliferated slower during the first stage, than the OA women (31.5+/-2.6 and 21.4+/-1.3 days, respectively, p<0.05). The OP group secreted significantly higher OPG protein levels than the OA women (10...
January 2009: Journal of Steroid Biochemistry and Molecular Biology
M Giner, M J Montoya, M A Vázquez, M J Rios, R Moruno, M J Miranda, R Pérez-Cano
The OPG/RANKL system in primary cultures of human osteoblasts has been studied by different authors. However, very few studies have been performed on gene expression of RANKL and OPG at different stages of maturation on human osteoblast cultures. The effect of 17- beta-estradiol and 1,25dihydroxyvitamin D3 on the OPG/RANKL system is not known during the different states of cellular maturation. In this work we quantified OPG and RANKL protein levels (ELISA) and the mRNA of OPG, RANKL, collagen type I, alkaline phosphatase, and osteocalcin (semi-quantitative RT-PCR) in human osteoblasts...
December 2008: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Michiyo Kobayashi-Sakamoto, Emiko Isogai, Kimiharu Hirose, Itsuo Chiba
Osteoprotegerin (OPG) is a decoy receptor for the receptor activator of nuclear factor kappaB ligand (RANKL). However, the role of OPG in the endothelium remains unknown. In this study, we demonstrate that OPG stimulates the proliferation and migration of human microvascular endothelial cells (HMVECs). In addition, we show that treatment with integrin alpha(v)beta(3) or integrin alpha(v)beta(5) blocking antibody inhibits endothelial cell migration. In contrast, treatment with anti-alpha(v)beta(3) antibody or anti-alpha(v)beta(5) antibody alone did not inhibit OPG-induced proliferation...
November 2008: Microvascular Research
I Breitkreutz, M S Raab, S Vallet, T Hideshima, N Raje, C Mitsiades, D Chauhan, Y Okawa, N C Munshi, P G Richardson, K C Anderson
Osteolytic bone disease in multiple myeloma (MM) is caused by enhanced osteoclast (OCL) activation and inhibition of osteoblast function. Lenalidomide and bortezomib have shown promising response rates in relapsed and newly diagnosed MM, and bortezomib has recently been reported to inhibit OCLs. We here investigated the effect of lenalidomide on OCL formation and osteoclastogenesis in comparison with bortezomib. Both drugs decreased alpha V beta 3-integrin, tartrate-resistant acid phosphatase-positive cells and bone resorption on dentin disks...
October 2008: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Stig S Jakobsen, A Larsen, M Stoltenberg, J M Bruun, K Soballe
Insertion of metal implants is associated with a possible change in the delicate balance between pro- and anti-inflammatory proteins, probably leading to an unfavourable predominantly pro-inflammatory milieu. The most likely cause is an inappropriate activation of macrophages in close relation to the metal implant and wear-products. The aim of the present study was to compare surfaces of as-cast and wrought Cobalt-Chrome-Molybdenum (CoCrMo) alloys and Titanium-Aluminium-Vanadium (TiAlV) alloy when incubated with mouse macrophage J774A...
2007: European Cells & Materials
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