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

Haas, Stefanie; Straub, Rainer H.

doi:10.1186/ar3852

Cited by 64 publications

(56 citation statements)

References 41 publications

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“…Evidence demonstrated mice with mutant clock genes exhibited altered regulation of bone volume (8) and increasing susceptibility to inflammatory arthritis (10). Previous study showed expression of clock protein or gene in synovial tissue and cells from OA and RA patients (34), however, no studies have addressed how clock genes changed in articular cartilage of patients with OA.…”

Section: Discussionmentioning

confidence: 98%

Clock Gene Bmal1 Modulates Human Cartilage Gene Expression by Crosstalk With Sirt1

et al. 2016

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The critical regulation of the peripheral circadian gene implicated in osteoarthritis (OA) has been recently recognized; however, the causative role and clinical potential of the peripheral circadian rhythm attributable to such effects remain elusive. The purpose of this study was to elucidate the role of a circadian gene Bmal1 in human cartilage and pathophysiology of osteoarthritis. In our present study, the mRNA and protein levels of circadian rhythm genes, including nicotinamide adenine dinucleotide oxidase (NAD(+)) and sirtuin 1 (Sirt1), in human knee articular cartilage were determined. In OA cartilage, the levels of both Bmal1 and NAD(+) decreased significantly, which resulted in the inhibition of nicotinamide phosphoribosyltransferase activity and Sirt1 expression. Furthermore, the knockdown of Bmal1 was sufficient to decrease the level of NAD(+) and aggravate OA-like gene expression changes under the stimulation of IL-1β. The overexpression of Bmal1 relieved the alteration induced by IL-1β, which was consistent with the effect of the inhibition of Rev-Erbα (known as NR1D1, nuclear receptor subfamily 1, group D). On the other hand, the transfection of Sirt1 small interfering RNA not only resulted in a reduction of the protein expression of Bmal1 and a moderate increase of period 2 (per2) and Rev-Erbα but also further exacerbated the survival of cells and the expression of cartilage matrix-degrading enzymes induced by IL-1β. Overexpression of Sirt1 restored the metabolic imbalance of chondrocytes caused by IL-1β. These observations suggest that Bmal1 is a key clock gene to involve in cartilage homeostasis mediated through sirt1 and that manipulating circadian rhythm gene expression implicates an innovative strategy to develop novel therapeutic agents against cartilage diseases.

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Section: Discussionmentioning

confidence: 98%

Clock Gene Bmal1 Modulates Human Cartilage Gene Expression by Crosstalk With Sirt1

et al. 2016

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“…55,58 Additionally, TNF-α and IL-1β can suppress the expression of the circadian gene Per as well as the clock-controlled genes D site of albumin promoter [albumin D-box]-binding protein ( Dbp ), thyrotroph embryonic factor (Tef ), and hepatic leukemia factor ( Hlf ). 61,62 Haas and Straub 25 also found that TNF-α inhibited the expression of Clock , Per1 , and Per2 in synovial tissue cells isolated from osteoarthritis patients, whereas TNF-α and IL-1β increased the expression of these genes in RA synoviocytes. 25 Persistent disruption of the circadian rhythms has been closely associated with diseases in which chronic inflammation is among the principal pathological features, 63 and elements of the immune system implicated in the chronic inflammation have been shown to be under circadian control.…”

Section: Regulation Of Cytokines and Oxidative Stress Response Bmentioning

confidence: 92%

“…61,62 Haas and Straub 25 also found that TNF-α inhibited the expression of Clock , Per1 , and Per2 in synovial tissue cells isolated from osteoarthritis patients, whereas TNF-α and IL-1β increased the expression of these genes in RA synoviocytes. 25 Persistent disruption of the circadian rhythms has been closely associated with diseases in which chronic inflammation is among the principal pathological features, 63 and elements of the immune system implicated in the chronic inflammation have been shown to be under circadian control. Kouri et al 64 found clock gene expression to be disrupted in synoviocytes isolated from RA patients, with increased expression of REV-ERBα and the relative phase differences between BMAL1 and PER1 to be altered.…”

Section: Regulation Of Cytokines and Oxidative Stress Response Bmentioning

confidence: 92%

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The Potential of Circadian Realignment in Rheumatoid Arthritis

Rao

Pierre

Schlesinger

et al. 2016

Crit Rev Biomed Eng

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In this short review, we discuss evidence supporting the modulation of peripheral circadian systems as a therapeutic strategy for rheumatoid arthritis (RA). We first review the role of proinflammatory cytokines and oxidative stress, two of the primary mediators of chronic inflammation in RA, and their regulation by circadian clock machinery. We further highlight the role of environmental and metabolic signals in regulating the central and peripheral circadian clocks, with an emphasis on seasonal variations in photoperiod and rhythmic metabolic input, respectively. Finally, we hypothesize that the entrainment and realignment of peripheral clock rhythms have the ability to modulate these mediators, improving clinical outcomes in RA patients. Our discussion emphasizes the use of light therapy and time-restricted feeding for entraining peripheral clocks either via the entrainment of the central circadian clock in suprachiasmatic nuclei (SCN) or directly by uncoupling the peripheral circadian clocks from SCN. In doing so, we highlight the use of nonpharmacologic interventions as a potential strategy for improving clinical outcomes in chronic inflammatory conditions such as RA.

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“…These clocks regulate the circadian rhythms of inflammatory innate immune functions [13, 14]. Recently, Haas and Straub [15] described daily Bmal1 and Per1 rhythms in synovial fibroblasts of healthy subjects. Expression of clock proteins and their transcripts such as Bmal1 , Clock , Per1 , and Per2 has also been reported in synovial cells and tissues of patients with osteoarthritis and RA [16].…”

Section: Introductionmentioning

confidence: 99%

Peripheral Neuroimmunoendocrine Interactions: Contribution of TNFRp55 to the Circadian Synchronization of Progesterone and Cytokine Production in Joints of Mice in Late Pregnancy

Arias

Mayordomo

Silva

et al. 2018

Neuroimmunomodulation

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Objective: Circadian rhythms are generated by the suprachiasmatic nucleus of the hypothalamus and involve rhythmic expression of clock genes and proteins. This rhythmicity is transferred to peripheral tissues by neural and hormonal signals. Late pregnancy is considered a state of inflammation which impacts on peripheral tissues such as joints. Tumor necrosis factor (TNF) mediates inflammatory and circadian responses through its p55 receptor (TNFRp55). Neuroimmunoendocrine interactions in joints have not been studied completely. The purpose of this study was to analyze these interactions, investigating the circadian rhythms of progesterone (Pg) and pro- and anti-inflammatory cytokines in the joints at the end of pregnancy (gestational day 18). Moreover, the impact of TNFRp55 deficiency on these temporal oscillations was explored. Methods: Wild-type and TNFRp55-deficient (KO) C57BL/6 mice were kept under constant darkness in order to study their endogenous circadian rhythms. The expression of the clock genes Bmal1 and Per1 at circadian time 7 was studied by reverse transcription polymerase chain reaction in the ankle joints of nonpregnant and pregnant (gestational day 18) mice. In late pregnancy, Pg and the cytokines interleukin 17 (IL-17), IL-6, and IL-10 were measured in the joints throughout a 24-h period by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Results: A significant increase in Bmal1 and Per1 mRNA expression was detected in the joints of pregnant KO mice. Furthermore, KO mice displayed a desynchronization of articular Pg and cytokine production. Conclusions: Our results show that TNF, via TNFRp55 signaling, modulates articular Pg and cytokine circadian rhythms in late pregnancy. These findings suggest a temporal neuroimmunoendocrine association in peripheral tissues in late pregnancy.

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

Cited by 64 publications

References 41 publications

Clock Gene Bmal1 Modulates Human Cartilage Gene Expression by Crosstalk With Sirt1

Clock Gene Bmal1 Modulates Human Cartilage Gene Expression by Crosstalk With Sirt1

The Potential of Circadian Realignment in Rheumatoid Arthritis

Peripheral Neuroimmunoendocrine Interactions: Contribution of TNFRp55 to the Circadian Synchronization of Progesterone and Cytokine Production in Joints of Mice in Late Pregnancy

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