178 research outputs found

    Adipokines and bone: enigma or paradigm?

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    Despite years of intense research in the field of adipokines and musculoskeletal system, there is still an open debate over the effect of certain adipokines, particularly leptin and adiponectin, on this system. Though, adipokine effects on bone turnover and density are still under deep investigation.Adipobiology 2011; 3: 51-52

    Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1

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    The objective of the present study was to investigate the effect of leptin, alone or in combination with IL-1, on nitric oxide synthase (NOS) type II activity in vitro in human primary chondrocytes, in the mouse chondrogenic ATDC5 cell line, and in mature and hypertrophic ATDC5 differentiated chondrocytes. For completeness, we also investigated the signalling pathway of the putative synergism between leptin and IL-1. For this purpose, nitric oxide production was evaluated using the Griess colorimetric reaction in culture medium of cells stimulated over 48 hours with leptin (800 nmol/l) and IL-1 (0.025 ng/ml), alone or combined. Specific pharmacological inhibitors of NOS type II (aminoguanidine [1 mmol/l]), janus kinase (JAK)2 (tyrphostin AG490 and Tkip), phosphatidylinositol 3-kinase (PI3K; wortmannin [1, 2.5, 5 and 10 μmol/l] and LY294002 [1, 2.5, 5 and 10 μmol/l]), mitogen-activated protein kinase kinase (MEK)1 (PD098059 [1, 5, 10, 20 and 30 μmol/l]) and p38 kinase (SB203580 [1, 5, 10, 20 and 30 μmol/l]) were added 1 hour before stimulation. Nitric oxide synthase type II mRNA expression in ATDC5 chondrocytes was investigated by real-time PCR and NOS II protein expression was analyzed by western blot. Our results indicate that stimulation of chondrocytes with IL-1 results in dose-dependent nitric oxide production. In contrast, leptin alone was unable to induce nitric oxide production or expression of NOS type II mRNA or its protein. However, co-stimulation with leptin and IL-1 resulted in a net increase in nitric oxide concentration over IL-1 challenge that was eliminated by pretreatment with the NOS II specific inhibitor aminoguanidine. Pretreatment with tyrphostin AG490 and Tkip (a SOCS-1 mimetic peptide that inhibits JAK2) blocked nitric oxide production induced by leptin/IL-1. Finally, wortmannin, LY294002, PD098059 and SB203580 significantly decreased nitric oxide production. These findings were confirmed in mature and hypertrophic ATDC5 chondrocytes, and in human primary chondrocytes. This study indicates that leptin plays a proinflammatory role, in synergy with IL-1, by inducing NOS type II through a signalling pathway that involves JAK2, PI3K, MEK-1 and p38 kinaseThis work was supported by grants from Spanish Ministry of Health (FIS 01/3137 and PI-020431). Oreste Gualillo and Francisca Lago are recipients of a research contract from Spanish Ministry of Health, Instituto de Salud Carlos III (EXP 00/3051 and 99/3040). Miguel Otero is a recipient of a predoctoral fellowship funded by Xunta de Galicia. Rocío Lago is a recipient of a fellowship funded by Instituto de Salud Carlos III (Red Temática G03/152)S

    Is there a common therapeutical strategy for bone joints and blood vessels?

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    Growing evidence demonstrated recently a rationale for the use of orally administered collagen hydrolysate (collagen peptides) in the therapy of patients with osteoarthritis or other arthrodegenerative disorders. At the same time, there is a need for an effective treatment for millions of people in the world with atherosclerosis and its complications mainly due to the rupture of fibrous (collagenous-muscle) cap of the atherosclerotic plaque. Aortic aneurysm dissection in the heritable connective tissue disorders like Marfan, Ehlers-Danlos and Loeys-Dietz syndromes should also be considered herein. This Dance round article argues that the clinical data of collagen hydrolysate and matrix metalloproteinases (e.g., MMP-2, -9) inhibitors might be translated from osteoarthritis to the therapy of atherosclerosis as fibrous plaque stabilizers – this would be a joint of bone joints and blood vessels in action

    New Perspectives in the Study of Intestinal Inflammation: Focus on the Resolution of Inflammation

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    Inflammation is an essential physiological process that is directed to the protection of the organism against invading pathogens or tissue trauma. Most of the existing knowledge related to inflammation is focused on the factors and mechanisms that drive the induction phase of this process. However, since the recognition that the resolution of the inflammation is an active and tightly regulated process, increasing evidence has shown the relevance of this process for the development of chronic inflammatory diseases, such as inflammatory bowel disease. For that reason, with this review, we aimed to summarize the most recent and interesting information related to the resolution process in the context of intestinal inflammation. We discussed the advances in the understanding of the pro-resolution at intestine level, as well as the new mediators with pro-resolutive actions that could be interesting from a therapeutic point of view

    Prolactin activates tyrosyl phosphorylation of insulin receptor substrate 1 and phosphatidylinositol-3-OH kinase

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    Prolactin (PRL) has been demonstrated to induce tyrosine phosphorylation and activation of the cytoplasmic tyrosine kinase JAK2. The present study represents an initial effort to identify the phosphorylation repertoire of the PRL receptor (PRLR). For this purpose we have modified the rat PRLR cDNA to encode an additional N-terminal epitope specifically designed to allow the rapid purification of the PRLR and associated proteins from transfected cells. The Flag-tagged PRLR was stably expressed in the human 293 cell line. PRL induced tyrosine phosphorylation of proteins of 85, 95, and 185 kDa from 10 to 30 min after PRL stimulation. Immunoblot analysis of immunoprecipitation indicates that p85 corresponds to the 85-kDa regulatory subunit of phosphatidylinositol (PI)-3' kinase, p95 to PRLR, and p185 to insulin receptor substrate 1 (IRS-1). Both PI-3' kinase and IRS-1 appear to associate with PRLR in a PRL-dependent manner. These results thus indicate that kinases other than JAK2, namely PI-3' kinase, are activated by PRL

    Adipokines and Osteoarthritis: Novel Molecules Involved in the Pathogenesis and Progression of Disease

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    Obesity has been considered a risk factor for osteoarthritis and it is usually accepted that obesity contributes to the development and progression of osteoarthritis by increasing mechanical load of the joints. Nevertheless, recent advances in the physiology of white adipose tissue evidenced that fat cells produce a plethora of factors, called adipokines, which have a critical role in the development of ostearthritis, besides to mechanical effects. In this paper, we review the role of adipokines and highlight the cellular and molecular mechanisms at play in osteoarthritis elicited by adipokines. We also emphasize how defining the role of adipokines has broadned our understanding of the diversity of factors involved in the genesis and progression of osteoarthritis in the hope of modifying it to prevent and treat diseases