scholarly journals The P2Y6 Receptor Stimulates Bone Resorption by Osteoclasts

Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3706-3716 ◽  
Author(s):  
Isabel R. Orriss ◽  
Ning Wang ◽  
Geoffrey Burnstock ◽  
Timothy R. Arnett ◽  
Alison Gartland ◽  
...  
Keyword(s):  
Cell Function ◽  
Bone Cell ◽  
Extracellular Nucleotides ◽  
P2y6 Receptor ◽  
Tomographic Analysis ◽  
G Protein Coupled ◽  
Resorptive Activity

Accumulating evidence indicates that extracellular nucleotides, signaling through P2 receptors, play a significant role in bone remodeling. Osteoclasts (the bone-resorbing cell) and osteoblasts (the bone-forming cell) display expression of the G protein-coupled P2Y6 receptor, but the role of this receptor in modulating cell function is unclear. Here, we demonstrate that extracellular UDP, acting via P2Y6 receptors, stimulates the formation of osteoclasts from precursor cells, while also enhancing the resorptive activity of mature osteoclasts. Furthermore, osteoclasts derived from P2Y6 receptor-deficient (P2Y6R−/−) animals displayed defective function in vitro. Using dual energy x-ray absorptiometry scanning and microcomputed tomographic analysis we showed that P2Y6R−/− mice have increased bone mineral content, cortical bone volume, and cortical thickness in the long bones and spine, whereas trabecular bone parameters were unaffected. Histomorphometric analysis showed the perimeter of the bone occupied by osteoclasts on the endocortical and trabecular surfaces was decreased in P2Y6R−/− mice. Taken together these results show the P2Y6 receptor may play an important role in the regulation of bone cell function in vivo.

scholarly journals The role of G-protein-coupled membrane estrogen receptor in mouse Leydig cell function—in vivo and in vitro evaluation

2018 ◽  
Vol 374 (2) ◽  
pp. 389-412 ◽  
Author(s):  
M. Kotula-Balak ◽  
P. Pawlicki ◽  
A. Milon ◽  
W. Tworzydlo ◽  
M. Sekula ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Leydig Cell ◽  
Cell Function ◽  
G Protein Coupled ◽  
Mouse Leydig Cell ◽  
Leydig Cell Function

From Mouse to Man: Redefining the Role of Insulin-Like Growth Factor-I in the Acquisition of Bone Mass

2003 ◽  
Vol 228 (3) ◽  
pp. 245-252 ◽  
Author(s):  
Shoshana Yakar ◽  
Clifford J. Rosen
Keyword(s):  
Growth Factor ◽  
Cell Function ◽  
Bone Cells ◽  
Bone Cell ◽  
Insulin Like Growth Factor ◽  
In Vivo Models ◽  
Igf I

The insulin-like growth factor system (IGF) has been linked to the process of bone acquisition through epidemiologic analyses of large cohorts and in vitro studies of bone cells. But the exact relationship between expression of IGF-I in bone and skeletal homeostasis or pathologic conditions, such as osteoporosis, remains poorly defined. Recent advances in genomic engineering have resulted in the development of better in vivo models to test the role of IGF-I during development and maintenance of the adult skeleton. It is now established that skeletal expression of IGF-I is critical for differentiative bone cell function. It may also be essential for the full anabolic effects of parathyroid hormone on trabecular bone and for some component of biomineralization. Evidence from conditional mutagenesis studies suggests that serum IGF-I may represent more than a storage depot or permissive factor during the final phase of skeletal acquisition. This work re-examines the original tenets of the “somatomedin hypothesis” in light of these newer mouse models and their remarkable skeletal phenotypes. The implications are far reaching and suggest that newer approaches for manipulating the IGF regulatory system may one day be useful as therapeutic adjuncts for the treatment of osteoporosis.

A Review on Melatonin’s Effects in Cancer: Potential Mechanisms

2018 ◽  
Vol 18 (7) ◽  
pp. 985-992 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Ertan Kucuksayan ◽  
Rana Cagla Akduman ◽  
Tomris Ozben
Keyword(s):  
Systematic Review ◽  
Antioxidant Activity ◽  
Membrane Receptors ◽  
Cancer Development ◽  
Secretory Product ◽  
Prevention And Treatment ◽  
G Protein Coupled

This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland secretory product, an evolutionarily highly conserved molecule; it is also an antioxidant and an impressive protector of mitochondrial bioenergetic activity. MLT is characterized by an ample range of activities, modulating the physiology and molecular biology of the cell. Its physiological functions relate principally to the interaction of G Protein-Coupled MT1 and MT2 trans-membrane receptors (GPCRs), a family of guanidine triphosphate binding proteins. MLT has been demonstrated to suppress the growth of various tumours both, in vivo and in vitro. In this review, we analyze in depth, the antioxidant activity of melatonin, aiming to illustrate the cancer treatment potential of the molecule, by limiting or reversing the changes occurring during cancer development and growth.

Clopidogrel (plavix), a P2Y12 receptor antagonist, inhibits bone cell function in vitro and decreases trabecular bone in vivo

Bone ◽  
2012 ◽  
Vol 50 ◽  
pp. S45
Author(s):  
S. Syberg ◽  
A. Brandao-Burch ◽  
J.J. Patel ◽  
M.O. Hajjawi ◽  
T.R. Arnett ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Trabecular Bone ◽  
Cell Function ◽  
Bone Cell ◽  
P2y12 Receptor ◽  
P2y12 Receptor Antagonist

scholarly journals Clopidogrel (Plavix), a P2Y12receptor antagonist, inhibits bone cell function in vitro and decreases trabecular bone in vivo

2012 ◽  
Vol 27 (11) ◽  
pp. 2373-2386 ◽  
Author(s):  
Susanne Syberg ◽  
Andrea Brandao-Burch ◽  
Jessal J Patel ◽  
Mark Hajjawi ◽  
Timothy R Arnett ◽  
...  
Keyword(s):  
Trabecular Bone ◽  
Cell Function ◽  
Bone Cell

scholarly journals Advances in Research on the Protective Mechanisms of Traditional Chinese Medicine (TCM) in Islet β Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Na Li ◽  
Hongli Zhang ◽  
Xiaohua Li
Keyword(s):  
Chinese Medicine ◽  
Cell Function ◽  
Animal Experiments ◽  
Cell Protection ◽  
Insulin Synthesis ◽  
Treatment Of Diabetes ◽  
Insulinoma Cells

The dysfunction and decreased number of islet β cells are central to the main pathogenesis of diabetes. Improving islet β cell function and increasing the number of β cells are effective approaches to treat diabetes and constitute the main direction of diabetes drug development. The role of Chinese medicine in the treatment of diabetes began to be recognized. In recent years, Chinese medicine monomers have been found to increase insulin synthesis and secretion, reduce β cell-apoptosis, and protect the function of β cells. The results of in vivo animal experiments and in vitro studies on insulinoma cells also suggested TCMs could promote the proliferation of pancreatic islet β cells and induce other cells differentiation or transdifferentiation to islet β cells. Thereby, they may play a role in the treatment of diabetes. In this paper, we will review islet β cell protection with TCMs and the related mechanisms found in recent studies. An in-depth explanation of the role of TCM in islet β cell protection can provide a theoretical basis and research ideas for the development of TCM-based diabetes treatment drugs.

scholarly journals The Role of Methionine Aminopeptidase 2 in Lymphangiogenesis

2020 ◽  
Vol 21 (14) ◽  
pp. 5148
Author(s):  
Rawnaq Esa ◽  
Eliana Steinberg ◽  
Dvir Dror ◽  
Ouri Schwob ◽  
Mehrdad Khajavi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Function ◽  
Loss Of Function ◽  
Methionine Aminopeptidase ◽  
Zebrafish Model ◽  
Lymphatic Capillary ◽  
Intracellular Enzyme

During the metastasis process, tumor cells invade the blood circulatory system directly from venous capillaries or indirectly via lymphatic vessels. Understanding the relative contribution of each pathway and identifying the molecular targets that affect both processes is critical for reducing cancer spread. Methionine aminopeptidase 2 (MetAp2) is an intracellular enzyme known to modulate angiogenesis. In this study, we investigated the additional role of MetAp2 in lymphangiogenesis. A histological staining of tumors from human breast-cancer donors was performed in order to detect the level and the localization of MetAp2 and lymphatic capillaries. The basal enzymatic level and activity in vascular and lymphatic endothelial cells were compared, followed by loss of function studies determining the role of MetAp2 in lymphangiogenesis in vitro and in vivo. The results from the histological analyses of the tumor tissues revealed a high MetAp2 expression, with detectable sites of co-localization with lymphatic capillaries. We showed slightly reduced levels of the MetAp2 enzyme and MetAp2 mRNA expression and activity in primary lymphatic cells when compared to the vascular endothelial cells. The genetic and biochemical manipulation of MetAp2 confirmed the dual activity of the enzyme in both vascular and lymphatic remodulation in cell function assays and in a zebrafish model. We found that cancer-related lymphangiogenesis is inhibited in murine models following MetAp2 inhibition treatment. Taken together, our study provides an indication that MetAp2 is a significant contributor to lymphangiogenesis and carries a dual role in both vascular and lymphatic capillary formation. Our data suggests that MetAp2 inhibitors can be effectively used as anti-metastatic broad-spectrum drugs.

Role of LPXRFamide peptide in the neuroendocrine regulation of reproduction in fish

2011 ◽  
Vol 6 (5) ◽  
pp. 853-860 ◽  
Author(s):  
Md. Shahjahan ◽  
Hironori Ando
Keyword(s):  
Gonadal Development ◽  
Gonadotropin Releasing Hormone ◽  
Fish Reproduction ◽  
Lower Vertebrates ◽  
Hypothalamic Control ◽  
G Protein Coupled ◽  
Made In

AbstractThe decapeptide gonadotropin-releasing hormone (GnRH) is the primary factor responsible for the hypothalamic control of gonadotropin (GTH) secretion. This review focuses on a family of neuropeptides, LPXRFamide (LPXRFa) peptides, which have been implicated in the regulation of GTH secretion. LPXRFa acts on the pituitary via a G protein-coupled receptor, LPXRFa-R, to enhance gonadal development and maintenance by increasing gonadotropin release and synthesis. Because LPXRFa exists and functions in several fish species, LPXRFa is considered to be a key neurohormone in fish reproduction control. The precursors to LPXRFamide peptides encoded plural LPXRFamide peptides and were highly divergent in vertebrates, particularly in lower vertebrates. Tissue distribution analyses indicated that LPXRFamide peptides were highly concentrated in the hypothalamus and other brainstem regions. In view of the localization and expression of LPXRFamide peptides in the hypothalamo-hypophysial system, LPXRFamide peptide in fish increase GTH release in vitro and in vivo. This review summarizes the advances made in our understanding of the biosynthesis, mode of action and functional significance of LPXRFa, a newly discovered key neurohormone.

scholarly journals Leukotrienes modulate secretion of progesterone and prostaglandins during the estrous cycle and early pregnancy in cattle: an in vivo study

Reproduction ◽  
2010 ◽  
Vol 140 (5) ◽  
pp. 767-776 ◽  
Author(s):  
Anna J Korzekwa ◽  
Mamadou M Bah ◽  
Andrzej Kurzynowski ◽  
Karolina Lukasik ◽  
Agnieszka Groblewska ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Estrous Cycle ◽  
Early Pregnancy ◽  
Luteal Phase ◽  
Reproductive Tract ◽  
Cell Function ◽  
Ovarian Cell

Recently, we showed that leukotrienes (LTs) regulate ovarian cell functionin vitro. The aim of this study was to examine the role of LTs in corpus luteum (CL) function during both the estrous cycle and early pregnancyin vivo. mRNA expression of LT receptors (BLTfor LTB4andCYSLTfor LTC4), and 5-lipoxygenase (5-LO) in CL tissue and their localization in the ovary were studied during the estrous cycle and early pregnancy. Moreover, concentrations of LTs (LTB4and C4) in the CL tissue and blood were measured.5-LOandBLTmRNA expression increased on days 16–18 of the cycle, whereasCYSLTmRNA expression increased on days 16–18 of the pregnancy. The level of LTB4was evaluated during pregnancy compared with the level of LTC4, which increased during CL regression. LT antagonists influenced the duration of the estrous cycle: the LTC4antagonist (azelastine) prolonged the luteal phase, whereas the LTB4antagonist (dapsone) caused earlier luteolysisin vivo. Dapsone decreased progesterone (P4) secretion and azelastine increased P4secretion during the estrous cycle. In summary, LT action in the bovine reproductive tract is dependent on LT type: LTB4is luteotropic during the estrous cycle and supports early pregnancy, whereas LTC4is luteolytic, regarded as undesirable in early pregnancy. LTs are produced/secreted in the CL tissue, influence prostaglandin function, and serve as important factors during the estrous cycle and early pregnancy in cattle.

scholarly journals Clinical Trial andIn VitroStudy for the Role of Cartilage and Synovia in Acute Articular Infection

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Elia R. Langenmair ◽  
Eva J. Kubosch ◽  
Gian M. Salzmann ◽  
Samuel Beck ◽  
Hagen Schmal
Keyword(s):  
Clinical Trial ◽  
Cell Function ◽  
Joint Infection ◽  
Synovial Fibroblasts ◽  
Joint Infections ◽  
Anti Inflammatory

Objective. Osteoarthritis is a long-term complication of acute articular infections. However, the roles of cartilage and synovia in this process are not yet fully understood.Methods. Patients with acute joint infections were enrolled in a prospective clinical trial and the cytokine composition of effusions compared in patients with arthroplasty (n= 8) or with intact joints (n= 67). Cytokines and cell function were also analyzed using a humanin vitromodel of joint infection.Results. Synovial IL-1βlevels were significantly higher in patients with arthroplasty (p= 0.004). Higher IL-1βconcentrations were also found in thein vitromodel without chondrocytes (p< 0.05). The anti-inflammatory cytokines IL-4 and IL-10 were consistently expressedin vivoandin vitro, showing no association with the presence of cartilage or chondrocytes. In contrast, FasL levels increased steadilyin vitro, reaching higher levels without chondrocytes (p< 0.05). Likewise, the viability of synovial fibroblasts (SFB) during infection was higher in the presence of chondrocytes. The cartilage-metabolism markers aggrecan and bFGF were at higher concentrations in intact joints, but also synthesized by SFB.Conclusions. Our data suggest an anti-inflammatory effect of cartilage associated with the SFBs’ increased resistance to infections, which displayed the ability to effectively synthesize cartilage metabolites.The trial is registered with DRKS00003536, MISSinG.

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