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Int J Mol Sci. 2019 Mar 11;20(5). pii: E1212. doi: 10.3390/ijms20051212.

Role of Norepinephrine in IL-1β-Induced Chondrocyte Dedifferentiation under Physioxia.

Author information

1
Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopaedic University Hospital Friedrichsheim gGmbH, Marienburgstr. 2, 60528 Frankfurt/Main, Germany. saskia.speichert@web.de.
2
Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopaedic University Hospital Friedrichsheim gGmbH, Marienburgstr. 2, 60528 Frankfurt/Main, Germany. natalie.molotkov@friedrichsheim.de.
3
Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopaedic University Hospital Friedrichsheim gGmbH, Marienburgstr. 2, 60528 Frankfurt/Main, Germany. karima.elbagdadi@friedrichsheim.de.
4
Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopaedic University Hospital Friedrichsheim gGmbH, Marienburgstr. 2, 60528 Frankfurt/Main, Germany. andrea.meurer@friedrichsheim.de.
5
Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopaedic University Hospital Friedrichsheim gGmbH, Marienburgstr. 2, 60528 Frankfurt/Main, Germany. frank.zaucke@friedrichsheim.de.
6
Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Orthopaedic University Hospital Friedrichsheim gGmbH, Marienburgstr. 2, 60528 Frankfurt/Main, Germany. zsuzsa.jenei-lanzl@friedrichsheim.de.

Abstract

As part of the pathogenesis of osteoarthritis (OA), chondrocytes lose their phenotype and become hypertrophic, or dedifferentiate, mainly driven by interleukin-1β (IL-1β). The contribution of other factors to the dedifferentiation process is not completely understood. Recent studies suggested a dose-dependent role for the sympathetic neurotransmitter norepinephrine (NE) in OA chondrocyte metabolism. Therefore, the aim of this study was to analyze the contribution of NE (10-8 M, 10-6 M) to human articular OA chondrocyte dedifferentiation in the absence or presence of IL-1β (0.5 ng/mL). Here, we demonstrate that OA chondrocytes express α2A-, α2C- and β2-adrenoceptors (AR) and show the characteristic shift towards a fibroblast-like shape at day 7 in physioxic monolayer culture. NE alone did not affect morphology but, in combination with IL-1β, markedly accelerated this shift. Moderate glycosaminoglycan (GAG) staining was observed in untreated and NE-treated cells, while IL-1β strongly decreased GAG deposition. IL-1β alone or in combination with NE decreased SOX9, type II collagen, COMP, and aggrecan, and induced MMP13 and ADAMTS4 gene expression, indicating an accelerated dedifferentiation. NE alone did not influence gene expression and did not modulate IL-1β-mediated effects. In conclusion, these results indicate that low-grade inflammation exerts a dominant effect on chondrocyte dedifferentiation and should be targeted early in OA therapy.

KEYWORDS:

adrenoceptors; chondrocytes; dedifferentiation; interleukin-1β; norepinephrine; osteoarthritis; physioxia

PMID:
30861996
PMCID:
PMC6429278
DOI:
10.3390/ijms20051212
[Indexed for MEDLINE]
Free PMC Article

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