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Do Neuroendocrine Peptides and Their Receptors Qualify as Novel Therapeutic Targets in Osteoarthritis?

Department of Orthopedic Surgery, Exp. Orthopedics, ZMB/Biopark 1, University of Regensburg, 93053 Regensburg, Germany
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(2), 367;
Received: 2 January 2018 / Revised: 22 January 2018 / Accepted: 23 January 2018 / Published: 26 January 2018
(This article belongs to the Special Issue Musculoskeletal Diseases Therapy)
PDF [1645 KB, uploaded 26 January 2018]


Joint tissues like synovium, articular cartilage, meniscus and subchondral bone, are targets for neuropeptides. Resident cells of these tissues express receptors for various neuroendocrine-derived peptides including proopiomelanocortin (POMC)-derived peptides, i.e., α-melanocyte-stimulating hormone (α-MSH), adrenocorticotropin (ACTH) and β-endorphin (β-ED), and sympathetic neuropeptides like vasoactive intestinal peptide (VIP) and neuropeptide y (NPY). Melanocortins attained particular attention due to their immunomodulatory and anti-inflammatory effects in several tissues and organs. In particular, α-MSH, ACTH and specific melanocortin-receptor (MCR) agonists appear to have promising anti-inflammatory actions demonstrated in animal models of experimentally induced arthritis and osteoarthritis (OA). Sympathetic neuropeptides have obtained increasing attention as they have crucial trophic effects that are critical for joint tissue and bone homeostasis. VIP and NPY are implicated in direct and indirect activation of several anabolic signaling pathways in bone and synovial cells. Additionally, pituitary adenylate cyclase-activating polypeptide (PACAP) proved to be chondroprotective and, thus, might be a novel target in OA. Taken together, it appears more and more likely that the anabolic effects of these neuroendocrine peptides or their respective receptor agonists/antagonists may be exploited for the treatment of patients with inflammatory and degenerative joint diseases in the future. View Full-Text
Keywords: proopiomelanocortin; alpha-MSH; VIP; NPY; osteoarthritis; neuroendocrine; PACAP proopiomelanocortin; alpha-MSH; VIP; NPY; osteoarthritis; neuroendocrine; PACAP

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Grässel, S.; Muschter, D. Do Neuroendocrine Peptides and Their Receptors Qualify as Novel Therapeutic Targets in Osteoarthritis? Int. J. Mol. Sci. 2018, 19, 367.

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