Adrenomedullin<sup>22–52</sup> combats inflammation and prevents systemic bone loss in murine collagen‐induced arthritis

Kioon, Marie Dominique Ah; Asensio, C.; Ea, Hang‐Korng; Velard, Frédéric; Uzan, Benjamin; Rullé, Sandrine; Bazille, Céline; Marty, Caroline; Falgarone, Géraldine; Nguyen, Christelle; Collet, Corinne; Launay, Jean‐Marie; Cohen‐Solal, Martine; Lioté, Frédéric

doi:10.1002/art.33426

Cited by 14 publications

(17 citation statements)

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“…Other publications seem to support our findings when properly interpreted. For instance a study used the peptide fragment AM 22−52 , trying to take advantage of its immunomodulatory action, and found that it prevented bone loss in a model of collagen-induced arthritis (Ah Kioon et al, 2012 ). As explained above, this fragment is an AM inhibitor and, as such, it has similar effects to our small molecule inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

et al. 2016

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Despite recent advances in the understanding and treatment options for osteoporosis, this condition remains a serious public health issue. Adrenomedullin (AM) is a regulatory peptide with reported activity on bone remodeling. To better understand this relationship we built an inducible knockout for AM. An outstanding feature of knockout mice is their heavier weight due, in part, to the presence of denser bones. The femur of knockout animals was denser, had more trabeculae, and a thicker growth plate than wild type littermates. The endocrine influence of AM on bone seems to be elicited through an indirect mechanism involving, at least, the regulation of insulin, glucose, ghrelin, and calcitonin gene-related peptide (CGRP). To confirm the data we performed a pharmacological approach using the AM inhibitor 16311 in a mouse model of osteoporosis. Ovariectomized females showed significant bone mass loss, whereas ovariectomized females treated with 16311 had similar bone density to sham operated females. In conclusion, we propose the use of AM inhibitors for the treatment of osteoporosis and other conditions leading to the loss of bone mass.

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Section: Discussionmentioning

confidence: 99%

Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

et al. 2016

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“…Target sites comprise the cardiorespiratory organs and immune cells . Adrenomedullin has been shown to be anti‐inflammatory in animal models of sepsis, pancreatitis, arthritis and colonic inflammation . Adrenomedullin was also reported to inhibit cell proliferation and inflammatory mediator secretion by synovial fibroblasts of rheumatoid arthritis patients .…”

Section: Anti‐inflammatory Neuropeptidesmentioning

confidence: 99%

“…Target sites comprise the cardiorespiratory organs and immune cells [116]. Adrenomedullin has been shown to be anti-inflammatory in animal models of sepsis, pancreatitis, arthritis and colonic inflammation [117][118][119][120].…”

Section: Adrenomedullinmentioning

confidence: 99%

Neuropeptide receptors as potential drug targets in the treatment of inflammatory conditions

Pintér

Pozsgai

Hajna

et al. 2013

Brit J Clinical Pharma

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Cross-talk between the nervous, endocrine and immune systems exists via regulator molecules, such as neuropeptides, hormones and cytokines. A number of neuropeptides have been implicated in the genesis of inflammation, such as tachykinins and calcitonin gene-related peptide. Development of their receptor antagonists could be a promising approach to anti-inflammatory pharmacotherapy. Anti-inflammatory neuropeptides, such as vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, a-melanocyte-stimulating hormone, urocortin, adrenomedullin, somatostatin, cortistatin, ghrelin, galanin and opioid peptides, are also released and act on their own receptors on the neurons as well as on different inflammatory and immune cells. The aim of the present review is to summarize the most prominent data of preclinical animal studies concerning the main pharmacological effects of ligands acting on the neuropeptide receptors. Promising therapeutic impacts of these compounds as potential candidates for the development of novel types of anti-inflammatory drugs are also discussed.

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“…Besides its potent vasodilatory and hypotensive effects, adrenomedullin also has an anti-inflammatory effect [ 5 ]. Adrenomedullin can inhibit the production of tumor necrosis factor-α (TNF-α) from activated macrophages [ 6 ] and was found to abrogate inflammation and alleviate systemic bone loss in murine collagen-induced arthritis [ 7 ]. Adrenomedullin may be involved in the pathogenesis of OA through the anti-inflammatory effect.…”

Section: Introductionmentioning

confidence: 99%

Correlation of Adrenomedullin Concentrations with Knee Osteoarthritis Grade

Liu

Huang

et al. 2016

Med Sci Monit

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BackgroundAdrenomedullin, a recently identified myokine, has an anti-inflammatory effect. Therefore, we aimed to assess the correlation of adrenomedullin concentrations with the presence and grade of severity of knee osteoarthritis (OA).Material/MethodsWe recruited 187 knee OA patients and 109 healthy subjects. The severity of OA was evaluated using the Kellgren-Lawrence grading system.ResultsCompared with the control group, the knee OA group revealed markedly higher adrenomedullin concentrations. Serum and synovial fluid (SF) adrenomedullin concentrations increased with increased KL grades.ConclusionsSerum and SF adrenomedullin concentrations show a correlation with the severity of knee OA.

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Adrenomedullin^22–52 combats inflammation and prevents systemic bone loss in murine collagen‐induced arthritis

Abstract: Conclusion. Our findings indicate that adrenomedullin 22-52 , which has no vasoactive or tumorinducing effects, is a potent antiinflammatory and boneprotective agent in this arthritis model.

Cited by 14 publications

References 44 publications

Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

Neuropeptide receptors as potential drug targets in the treatment of inflammatory conditions

Correlation of Adrenomedullin Concentrations with Knee Osteoarthritis Grade

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Adrenomedullin22–52 combats inflammation and prevents systemic bone loss in murine collagen‐induced arthritis

Abstract: Conclusion. Our findings indicate that adrenomedullin 22-52 , which has no vasoactive or tumorinducing effects, is a potent antiinflammatory and boneprotective agent in this arthritis model.

Cited by 14 publications

References 44 publications

Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

Neuropeptide receptors as potential drug targets in the treatment of inflammatory conditions

Correlation of Adrenomedullin Concentrations with Knee Osteoarthritis Grade

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Product

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Adrenomedullin^22–52 combats inflammation and prevents systemic bone loss in murine collagen‐induced arthritis