Graessel, Susanne and Opolka, Alfred and Anders, Sven and Straub, Rainer H. and Grifka, Joachim and Luger, Thomas A. and Boehm, Markus (2009) The Melanocortin System in Articular Chondrocytes Melanocortin Receptors, Pro-opiomelanocortin, Precursor Proteases, and a Regulatory Effect of alpha-Melanocyte-Stimulating Hormone on Proinflammatory Cytokines and Extracellular Matrix Components. ARTHRITIS AND RHEUMATISM, 60 (10). pp. 3017-3027. ISSN 0004-3591, 1529-0131
Full text not available from this repository. (Request a copy)Abstract
Objective. The pro-opiomelanocortin (POMC)derived neuropeptide a-melanocyte-stimulating hormone (alpha-MSH) mediates its effects via melanocortin (MC) receptors. This study was carried out to investigate the expression patterns of the MC system and the effects of alpha-MSH in human articular chondrocytes. Methods. Articular chondrocytes established from human osteoarthritic joint cartilage were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting for the expression of MC receptors, POMC, and prohormone convertases (PCs). MC-1 receptor (MC-1R) expression in articular cartilage was further studied by immunohistochemistry. Ca2+ and cAMP assays were used to monitor alpha-MSH signaling, while studies of alpha-MSH function were performed in cultures with chondrocyte micromass pellets stimulated with alpha-MSH. Expression of cytokines and extracellular matrix (ECM) components was determined by real-time RT-PCR, Western immunoblotting, and enzyme-linked immunosorbent assays. Results. MC-1R expression was detected in articular chondrocytes in vitro and in articular cartilage in situ. In addition, expression of transcripts for MC-2R, MC-5R, POMC, and PCs was detected in articular chondrocytes. Stimulation with alpha-MSH increased the levels of intracellular cAMP, but not Ca2+, in chondrocytes. Both messenger RNA and protein expression of various proinflammatory cytokines, collagens, matrix metal loproteinases (MMPs), and SOX9 was modulated by alpha-MSH. Conclusion. Human articular chondrocytes are target cells for alpha-MSH. The effects of alpha-MSH on expression of cytokines and MMPs suggest that this neuropeptide plays a role in inflammatory and degenerative processes in cartilage. It is conceivable that inflammatory reactions can be mitigated by the induction of endogenous MCs or administration of alpha-MSH to the affected joints. The induction pattern of regulatory and structural ECM components such as collagens as well as SOX9 and anabolic and catabolic cytokines points to a function of alpha-MSH as a trophic factor in skeletal development during endochondral ossification rather than as a factor in homeostasis of permanent cartilage.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN OSTEOARTHRITIC CARTILAGE; CORTICOTROPIN-RELEASING HORMONE; MESSENGER-RNA; ENHANCES CHONDROGENESIS; GENE-EXPRESSION; HUMAN SKIN; IN-SITU; CELLS; COLLAGEN; CALCIUM; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Orthopädie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Sep 2020 11:52 |
| Last Modified: | 03 Sep 2020 11:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28292 |
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