Osteoarthritis

P138 - α-MSH Modulates Senescence and Inflammatory State of Human Osteoarthritic Chondrocytes

Disclosure
No Significant Commercial Relationship
Presentation Topic
Osteoarthritis
Poster Rating
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Abstract

Purpose

Osteoarthritis (OA) is a degenerative joint disease which is closely associated with age. OA causes cartilage loss and structural damage in all joint tissues, with inflammatory mediators playing a critical role. The α-melanocyte–stimulating hormone (α-MSH) is a melanocortin (MC) peptide which mediates its effects via MC receptors (MCR). Beyond pigment induction, α-MSH has several anti-inflammatory and chondro-protective effects mitigating age-related processes. Abrogated MC1R signalling lead to a more severe OA-pathology in a murine surgical OA model. Therefore, the aim of this study was to analyse the effect of α-MSH on senescent human OA chondrocytes.

Methods and Materials

Chondrocytes and synovial fluid (SF) were obtained from OA patients. Chondrocytes, cultivated in 2D monolayers, were incubated with α-MSH and treated with doxorubicin, to induce a senescent phenotype. Induction of senescence was verified by senescence-associated ß-galactosidase (SA-ß-Gal) activity, caspase 3/7 activity and senescence-marker expression. The expression and secretion of pro-inflammatory cytokines and complement markers were analysed in SF, cell lysates and supernatants by qPCR, Western Blot and Multiplex-ELISA. OA chondrocytes were genotyped for MC1R loss-of-function polymorphisms.

Results

We induced SA-ß-Gal expression in all doxorubicin-treated human chondrocytes and did not observe any changes in apoptosis rate. We detected an increase in CDK-inhibitors p16 and p21, as well as increased catabolic markers IL-6, MMP-3, MMP-13, complement components C3, C3a and complement factor B (CFB). Senescent OA chondrocytes incubated with α-MSH showed a decreased inflammatory expression pattern and a reduced secretion of anaphylatoxin C3a in cell supernatants. α-MSH, IL-1ß and IL-6, as well as C3a were altered in SF between OA patients. Different MC1R polymorphisms could be observed in OA samples.

Conclusion

These in vitro data indicated an anti-inflammatory and possibly anti-ageing effect of α-MSH on senescence-induced human osteoarthritic chondrocytes. A correlation between the effect of α-MSH and genetic MC1R variations on OA chondrocyte metabolism needs to be further investigated.

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