title: Inflammation and linear bone growth: the inhibitory role of SOCS2 on GH/IGF-1 signaling.
abstract: Linear bone growth is widely recognized to be adversely affected in children with chronic kidney disease (CKD) and other chronic inflammatory disorders. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) pathway is anabolic to the skeleton and inflammatory cytokines compromise bone growth through a number of different mechanisms, which include interference with the systemic as well as the tissue-level GH/IGF-1 axis. Despite attempts to promote growth and control disease, there are an increasing number of reports of the persistence of poor growth in a substantial proportion of patients receiving rhGH and/or drugs that block cytokine action. Thus, there is an urgent need to consider better and alternative forms of therapy that are directed specifically at the mechanism of the insult which leads to abnormal bone health. Suppressor of cytokine signaling 2 (SOCS2) expression is increased in inflammatory conditions including CKD, and is a recognized inhibitor of GH signaling. Therefore, in this review, we will focus on the premise that SOCS2 signaling represents a critical pathway in growth plate chondrocytes through which pro-inflammatory cytokines alter both GH/IGF-1 signaling and cellular function.
authors.affiliation: Division of Developmental Biology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK. colin.farquharson@roslin.ed.ac.uk
authors.forename: Colin
authors.initials: C
authors.lastname: Farquharson
authors.forename: S Faisal
authors.initials: SF
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001827:Body Height; D001846:Bone Development; D001842:Bone and Bones / Q000378:metabolism* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D006130:Growth Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006132:Growth Plate / Q000254:growth & development / Q000378:metabolism; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016014:Linear Models; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C106643:SOCS2 protein, human; D050826:Suppressor of Cytokine Signaling Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I