The Activity of Peptides of the Calcitonin Family in Bone

Calcitonin was discovered over 50 yr ago as a new hormone that rapidly lowers circulating calcium levels. This effect is caused by the inhibition of calcium efflux from bone, as calcitonin is a potent inhibitor of bone resorption. Calcitonin has been in clinical use for conditions of accelerated bone turnover, including Paget’s disease and osteoporosis; although in recent years, with the development of drugs that are more potent inhibitors of bone resorption, its use has declined. A number of peptides that are structurally similar to calcitonin form the calcitonin family, which currently includes calcitonin gene–related peptides (αCGRP and βCGRP), amylin, adrenomedullin, and intermedin. Apart from being structurally similar, the peptides signal through related receptors and have some overlapping biological activities, although other activities are peptide specific. In bone, in vitro studies and administration of the peptides to animals generally found inhibitory effects on osteoclasts and bone resorption and positive effects on osteoblasts and bone formation. Surprisingly, studies in genetically modified mice have demonstrated that the physiological role of calcitonin appears to be the inhibition of osteoblast activity and bone turnover, whereas amylin inhibits osteoclast activity. The review article focuses on the activities of peptides of the calcitonin family in bone and the challenges in understanding the relationship between the pharmacological effects and the physiological roles of these peptides.

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Quercetin-Based Nanocomposites as a Tool to Improve Dental Disease Management

Biomedicines ◽

10.3390/biomedicines8110504 ◽

2020 ◽

Vol 8 (11) ◽

pp. 504

Author(s):

Giuseppe Angellotti ◽

Denise Murgia ◽

Giuseppina Campisi ◽

Viviana De Caro

Keyword(s):

Dental Implants ◽

Antibacterial Activities ◽

Missing Teeth ◽

Positive Effects ◽

Functionalized Surfaces ◽

Osteoblast Activity ◽

Experimental Findings

The restoration and prosthetic rehabilitation of missing teeth are commonly performed using dental implants, which are extremely effective and long-lasting techniques due to their osteointegration ability with the preimplant tissues. Quercetin is a phytoestrogen-like flavonoid well known for its several positive effects on human health, mostly linked to the anti-inflammatory, antioxidant, and antibacterial activities against both Gram-positive and Gram-negative bacteria. Moreover, many studies in dentistry and the maxillofacial fields have highlighted the positive effects of quercetin on osteogenesis, acting on osteoblast activity and angiogenetic process, and promoting soft and hard tissue regeneration. This review focuses on the role of quercetin on the healing and restoration of bony defects, considering the experimental findings of its application both in vitro and in vivo as a mere compound or in association with scaffolds and dental implants having functionalized surfaces.

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Regulation of Bone Mass and Bone Turnover by Neuronal Nitric Oxide Synthase

Endocrinology ◽

10.1210/en.2004-0205 ◽

2004 ◽

Vol 145 (11) ◽

pp. 5068-5074 ◽

Cited By ~ 64

Author(s):

Robert J. van’t Hof ◽

Jeny MacPhee ◽

Helene Libouban ◽

Miep H. Helfrich ◽

Stuart H. Ralston

Keyword(s):

Nitric Oxide ◽

Bone Turnover ◽

Cell Function ◽

Bone Cells ◽

Physiological Role ◽

Bone Cell ◽

Nodule Formation ◽

Mineral Density

Abstract Nitric oxide (NO) is produced by NO synthase (NOS) and plays an important role in the regulation of bone cell function. The endothelial NOS isoform is essential for normal osteoblast function, whereas the inducible NOS isoform acts as a mediator of cytokine effects in bone. The role of the neuronal isoform of NOS (nNOS) in bone has been studied little thus far. Therefore, we investigated the role of nNOS in bone metabolism by studying mice with targeted inactivation of the nNOS gene. Bone mineral density (BMD) was significantly higher in nNOS knockout (KO) mice compared with wild-type controls, particularly the trabecular BMD (P < 0.01). The difference in BMD between nNOS KO and control mice was confirmed by histomorphometric analysis, which showed a 67% increase in trabecular bone volume in nNOS KO mice when compared with controls (P < 0.001). This was accompanied by reduced bone remodeling, with a significant reduction in osteoblast numbers and bone formation surfaces and a reduction in osteoclast numbers and bone resorption surfaces. Osteoblasts from nNOS KO mice, however, showed increased levels of alkaline phosphatase and no defects in proliferation or bone nodule formation in vitro, whereas osteoclastogenesis was increased in nNOS KO bone marrow cultures. These studies indicate that nNOS plays a hitherto unrecognized but important physiological role as a stimulator of bone turnover. The low level of nNOS expression in bone and the in vitro behavior of nNOS KO bone cells indicate that these actions are indirect and possibly mediated by a neurogenic relay.

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Metabolomics of Healthy Berry Fruits

Current Medicinal Chemistry ◽

10.2174/0929867323666161206100006 ◽

2019 ◽

Vol 25 (37) ◽

pp. 4888-4902 ◽

Cited By ~ 3

Author(s):

Gilda D'Urso ◽

Sonia Piacente ◽

Cosimo Pizza ◽

Paola Montoro

Keyword(s):

Biological Activities ◽

Biologically Active ◽

In Vivo Studies ◽

Bioactive Metabolites ◽

Active Metabolites ◽

Positive Effects ◽

Cell Functions ◽

Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

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Role of interleukins in the pathogenesis of pulmonary fibrosis

Cell Death Discovery ◽

10.1038/s41420-021-00437-9 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yi Xin She ◽

Qing Yang Yu ◽

Xiao Xiao Tang

Keyword(s):

Pulmonary Fibrosis ◽

Therapeutic Strategy ◽

Future Directions ◽

Regulation Mechanisms ◽

Underlying Mechanisms ◽

Multiple Cells ◽

The Relationship

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

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In vitro biological activities and in vivo hepatoprotective role of brown algae-isolated fucoidans

Environmental Science and Pollution Research ◽

10.1007/s11356-020-11892-9 ◽

2021 ◽

Author(s):

Marwa E. Atya ◽

Amr El-Hawiet ◽

Mohamed A. Alyeldeen ◽

Doaa A. Ghareeb ◽

Mohamed M. Abdel-Daim ◽

...

Keyword(s):

Brown Algae ◽

Biological Activities

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The Diffusion Mechanism of Megaproject Citizenship Behavior: The Role of Institutional Isomorphism

Sustainability ◽

10.3390/su13158123 ◽

2021 ◽

Vol 13 (15) ◽

pp. 8123

Author(s):

Delei Yang ◽

Jun Zhu ◽

Qingbin Cui ◽

Qinghua He ◽

Xian Zheng

Keyword(s):

Structural Equation ◽

Diffusion Mechanism ◽

Vital Role ◽

Citizenship Behavior ◽

Equation Modeling ◽

Positive Effects ◽

Diffusion Limited ◽

The Relationship ◽

Mimetic Isomorphism

Megaproject citizenship behavior (MCB) has been confirmed to a play vital role on megaproject performance. Although current research has argued that institution elements have had an impact on MCB diffusion, limited studies have empirically investigated the distinct effectiveness of various institution elements on driving MCB’s widespread diffusion in construction megaprojects. Based on institution theory, this study proposes a theoretical model comprising institutional elements (i.e., normative and mimetic isomorphism), owner’s support, relationship-based trust, and their effect or impact on MCB’s diffusion. Based on 171 industrial questionnaires collected from managers of contractors and designers in megaprojects. Partial least squares structural equation modeling (PLS-SEM) was used to validate the established model. The results indicated that both normative and mimetic isomorphism have positive effects on facilitating MCB diffusion, and owner’s support has shown partial mediation in promoting MCB diffusion through normative isomorphism, as well as full mediation in the promoting of MCB diffusion through mimetic isomorphism. Meanwhile, relationship-based trust exerts a positive moderating effect on the relationship between mimetic isomorphism and MCB. This study extends current literature on driving MCB diffusion from the perspective of institutional theory, contributing by providing four implications for megaprojects managers to “buy in” more extensive MCB.

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Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

International Journal of Molecular Sciences ◽

10.3390/ijms22094717 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4717

Author(s):

Jin-Young Lee ◽

Da-Ae Kim ◽

Eun-Young Kim ◽

Eun-Ju Chang ◽

So-Jeong Park ◽

...

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Map Kinases ◽

Osteoclast Differentiation ◽

Dependent Manner ◽

Dual Action ◽

Dose Dependent ◽

Resorptive Activity

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

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Development of sensitivity to cAMP-inducing hormones in the rat stomach

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.247.3.g231 ◽

1984 ◽

Vol 247 (3) ◽

pp. G231-G239

Author(s):

C. Gespach ◽

Y. Cherel ◽

G. Rosselin

Keyword(s):

Biological Activities ◽

Physiological Role ◽

H2 Receptor Antagonist ◽

Adult Rats ◽

Gastric Glands ◽

Camp Generation ◽

Final Maturation ◽

Noncompetitive Inhibitor ◽

Regulatory Properties

Development of cAMP responses to secretin, pancreatic glucagon, and histamine was measured in gastric glands of fetal (day 20), postnatal (days 1-30), and adult rats (day 65). cAMP stimulation by these hormones was already detected on day 20 of gestation. cAMP generation showed biphasic variations during the 1st days of life and at the onset of weaning (day 20). Anticipated weaning at day 14 triggered precocious maturation (efficacies) of the cAMP-generating systems sensitive to secretin, glucagon, and histamine without changing the potencies of the hormones. During development, the general characteristics (potency and pharmacological or regulatory properties) of the receptor-cAMP systems studied were comparable with those evidenced in adult rats. At days 5, 20, and 65, vasoactive intestinal peptide and the peptide having N-terminal histidine and C-terminal isoleucine amide (PHI) were about 100 times less potent than secretin (EC50 = 1.5 X 10(-9) M secretin). The histamine action could be blocked by the competitive H2-receptor antagonist cimetidine (70-100% inhibition) as well as by the noncompetitive inhibitor somatostatin (37-62% inhibition). The data indicate that these regulatory hormones (secretin, glucagon(s), histamine, and somatostatin) might have a direct effect on gastric glands and may modulate their biological activities (metabolism, differentiation, proliferation, and exocrine and endocrine secretions) from the neonatal period in rats. The important physiological role of weaning on the final maturation of the cAMP-generating systems in rat gastric glands is underlined.

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Purinergic Modulation of Interleukin-1β Release from Microglial Cells Stimulated with Bacterial Endotoxin

Journal of Experimental Medicine ◽

10.1084/jem.185.3.579 ◽

1997 ◽

Vol 185 (3) ◽

pp. 579-582 ◽

Cited By ~ 342

Author(s):

Davide Ferrari ◽

Paola Chiozzi ◽

Simonetta Falzoni ◽

Stefania Hanau ◽

Francesco Di Virgilio

Keyword(s):

Plasma Membrane ◽

P2x7 Receptor ◽

Purinergic Receptor ◽

Present Report ◽

Physiological Role ◽

Bacterial Endotoxin ◽

Microglial Cells

Microglial cells express a peculiar plasma membrane receptor for extracellular ATP, named P2Z/P2X7 purinergic receptor, that triggers massive transmembrane ion fluxes and a reversible permeabilization of the plasma membrane to hydrophylic molecules of up to 900 dalton molecule weight and eventual cell death (Di Virgilio, F. 1995. Immunol. Today. 16:524–528). The physiological role of this newly cloned (Surprenant, A., F. Rassendren, E. Kawashima, R.A. North and G. Buell. 1996. Science (Wash. DC). 272:735–737) cytolytic receptor is unknown. In vitro and in vivo activation of the macrophage and microglial cell P2Z/P2X7 receptor by exogenous ATP causes a large and rapid release of mature IL-1β. In the present report we investigated the role of microglial P2Z/P2X7 receptor in IL-1β release triggered by LPS. Our data suggest that LPS-dependent IL-1β release involves activation of this purinergic receptor as it is inhibited by the selective P2Z/P2X7 blocker oxidized ATP and modulated by ATP-hydrolyzing enzymes such as apyrase or hexokinase. Furthermore, microglial cells release ATP when stimulated with LPS. LPS-dependent release of ATP is also observed in monocyte-derived human macrophages. It is suggested that bacterial endotoxin activates an autocrine/paracrine loop that drives ATP-dependent IL-1β secretion.

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