Disruption of rhythms of molecular clocks in primary synovial fibroblasts of patients with osteoarthritis and rheumatoid arthritis, role of IL-1β-TNFReport as inadecuate




Disruption of rhythms of molecular clocks in primary synovial fibroblasts of patients with osteoarthritis and rheumatoid arthritis, role of IL-1β-TNF - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 14:R122

First Online: 23 May 2012Received: 19 March 2012Revised: 20 April 2012Accepted: 23 May 2012

Abstract

IntroductionCircadian rhythms play an important role in the body and in single cells. Rhythms of molecular clocks have not been investigated in synovial fibroblasts SF of patients with osteoarthritis OA and rheumatoid arthritis RA. The study was initiated to fill this gap and to study effects of interleukin IL-1β-tumor necrosis factor TNF on rhythmicity in synovial fibroblasts of RA and OA patients.

MethodsThe presence of BMAL-1, CLOCK, Period 1 and Period 2 proteins in synovial tissue was investigated by immunofluorescence. The presence of mRNA of molecular clocks was studied during 72 h by qPCR. Characteristics of rhythms were studied with time series analysis.

ResultsBMAL-1, CLOCK, Period 1 and Period 2 proteins were abundantly present in synovial tissue of OA, RA and controls. Receiving synovial tissue at different operation time points during the day 8:00 am to 4:00 pm did not reveal a rhythm of BMAL-1 or Period 1 protein. In OASF and RASF, no typical rhythm curve of molecular clock mRNA was observed. Time series analysis identified a first peak between 2 and 18 hours after synchronization but a period was not detectable due to loss of rhythm. TNF inhibited mRNA of CLOCK, Period 1 and Period 2 in OASF, while IL-1β and TNF increased these factors in RASF. This was supported by dose-dependently increased levels in MH7A RA fibroblasts. In RASF, IL-1β and TNF shifted the first peak of BMAL-1 mRNA to later time points 8 h to 14 h.

ConclusionRhythmicity is not present in primary OASF and RASF, which is unexpected because fibroblasts usually demonstrate perfect rhythms during several days. This might lead to uncoupling of important cellular pathways.

AbbreviationsDAPI4-6-diamidino-2-phenylindole

HPAhypothalamic-pituitary-adrenal

ILinterleukin

OAosteoarthritis

RArheumatoid arthritis

SFsynovial fibroblasts

SNSsympathetic nervous system

TNFtumor necrosis factor.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3852 contains supplementary material, which is available to authorized users.

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Author: Stefanie Haas - Rainer H Straub

Source: https://link.springer.com/







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