Lorenz, Julia and Seebach, Elisabeth and Hackmayer, Gerit and Greth, Carina and Bauer, Richard J. and Kleinschmidt, Kerstin and Bettenworth, Dominik and Boehm, Markus and Grifka, Joachim and Graessel, Susanne (2014) Melanocortin 1 Receptor-Signaling Deficiency Results in an Articular Cartilage Phenotype and Accelerates Pathogenesis of Surgically Induced Murine Osteoarthritis. PLOS ONE, 9 (9): e105858. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Proopiomelanocortin-derived peptides exert pleiotropic effects via binding to melanocortin receptors (MCR). MCR-subtypes have been detected in cartilage and bone and mediate an increasing number of effects in diathrodial joints. This study aims to determine the role of MC1-receptors (MC1) in joint physiology and pathogenesis of osteoarthritis (OA) using MC1-signaling deficient mice (Mc1re/e). OA was surgically induced in Mc1re/e and wild-type (WT) mice by transection of the medial meniscotibial ligament. Histomorphometry of Safranin O stained articular cartilage was performed with non-operated controls (11 weeks and 6 months) and 4/8 weeks past surgery. mu CT-analysis for assessing epiphyseal bone architecture was performed as a longitudinal study at 4/8 weeks after OA-induction. Collagen II, ICAM-1 and MC1 expression was analysed by immunohistochemistry. Mc1re/e mice display less Safranin O and collagen II stained articular cartilage area compared to WT prior to OA-induction without signs of spontaneous cartilage surface erosion. This MC1-signaling deficiency related cartilage phenotype persisted in 6 month animals. At 4/8 weeks after OA-induction cartilage erosions were increased in Mc1re/e knees paralleled by weaker collagen II staining. Prior to OA-induction, Mc1re/e mice do not differ from WT with respect to bone parameters. During OA, Mc1re/e mice developed more osteophytes and had higher epiphyseal bone density and mass. Trabecular thickness was increased while concomitantly trabecular separation was decreased in Mc1re/e mice. Numbers of ICAM-positive chondrocytes were equal in non-operated 11 weeks Mc1re/e and WT whereas number of positive chondrocytes decreased during OA-progression. Unchallenged Mc1re/e mice display smaller articular cartilage covered area without OA-related surface erosions indicating that MC1-signaling is critical for proper cartilage matrix integrity and formation. When challenged with OA, Mc1re/e mice develop a more severe OA-pathology. Our data suggest that MC1-signaling protects against cartilage degradation and subchondral bone sclerosis in OA indicating a beneficial role of the POMC system in joint pathophysiology.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INTERCELLULAR-ADHESION MOLECULE-1; MELANOCYTE-STIMULATING HORMONE; SUBCHONDRAL BONE; ALPHA-MSH; CHONDROCYTES; PROOPIOMELANOCORTIN; HYALURONAN; PEPTIDES; CELLS; MODEL; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie Medicine > Lehrstuhl für Orthopädie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Aug 2019 09:18 |
| Last Modified: | 14 Aug 2019 09:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9566 |
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