Role of proopiomelanocortin-derived peptides and their receptors in the osteoarticular system: from basic to translational research.
Proopiomelanocortin (POMC)-derived peptides such as melanocortins and β-endorphin (β-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 β-ED, ACTH, or α-MSH. MCR subtypes, especially MC1R, MC2R (the ACTH receptor), MC3R, and MC4R, but also the μ-OR and δ-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, α-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.
Laboratory for Neuroendocrinology of the Skin and Interdisciplinary Endocrinology, Department of Dermatology, University of Münster, Von Esmarch-Strasse 58, D-48149 Münster, Germany. bohmm@uni-muenster.de
Markus
M
Böhm
Susanne
S
Grässel
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000378:metabolism*; D053486:Melanocortins / Q000494:pharmacology / Q000627:therapeutic use; D010003:Osteoarthritis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D001615:beta-Endorphin / Q000494:pharmacology / Q000627:therapeutic use
D053486:Melanocortins; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin