Role of Proopiomelanocortin-Derived Peptides and Their Receptors in the Osteoarticular System: From Basic to Translational Research

被引:62
作者
Boehm, Markus [1 ]
Graessel, Susanne [2 ]
机构
[1] Univ Munster, Dept Dermatol, Lab Neuroendocrinol Skin & Interdisciplinary Endo, D-48149 Munster, Germany
[2] Univ Regensburg, Dept Orthopaed Surg, D-93053 Regensburg, Germany
关键词
MELANOCYTE-STIMULATING-HORMONE; FAMILIAL GLUCOCORTICOID DEFICIENCY; HEREDITARY ADRENOCORTICAL UNRESPONSIVENESS; HUMAN ARTICULAR CHONDROCYTES; COLLAGEN-INDUCED-ARTHRITIS; INTRACELLULAR FREE CALCIUM; TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; ALPHA-MSH; BETA-ENDORPHIN;
D O I
10.1210/er.2011-1016
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Proopiomelanocortin (POMC)-derived peptides such as melanocortins and beta-endorphin (beta-ED) exert their pleiotropic effects via binding to melanocortin receptors (MCR) and opioid receptors (OR). There is now compelling evidence for the existence of a functional POMC system within the osteoarticular system. Accordingly, distinct cell types of the synovial tissue and bone have been identified to generate POMC-derived peptides like beta-ED, ACTH, or alpha-MSH. MCRsubtypes, especiallyMC1R, MC2R(the ACTH receptor), MC3R, and MC4R, but also the mu-OR and delta-OR, have been detected in various cells of the synovium, cartilage, and bone. The respective ligands of these POMC-derived peptide receptors mediate an increasing number of newly recognized biological effects in the osteoarticular system. These include bone mineralization and longitudinal growth, cell proliferation and differentiation, extracellular matrix synthesis, osteoprotection, and immunomodulation. Importantly, bone formation is also regulated by the central melanocortin system via a complex hormonal interplay with other organs and tissues involved in energy metabolism. Among the POMC-derived peptides examined in cell culture systems from osteoarticular tissue and in animal models of experimentally induced arthritis, alpha-MSH, ACTH, and MC3R-specific agonists appear to have the most promising antiinflammatory actions. The effects of these melanocortin peptides may be exploited in future for the treatment of patients with inflammatory and degenerative joint diseases. (Endocrine Reviews 33: 623-651, 2012)
引用
收藏
页码:623 / 651
页数:29
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