scholarly journals Timing metabolism in cartilage and bone: links between circadian clocks and tissue homeostasis

2019 ◽  
Vol 243 (3) ◽  
pp. R29-R46 ◽  
Author(s):  
Cátia F Gonçalves ◽  
Qing-Jun Meng
Keyword(s):  
Rheumatoid Arthritis ◽  
Circadian Rhythms ◽  
Circadian System ◽  
Tissue Homeostasis ◽  
Circadian Clocks ◽  
Clock System ◽  
Metabolic Functions ◽  
Biochemical Mechanisms ◽  
Skeletal Disorders ◽  
Bone Physiology

The circadian system in mammals is responsible for the temporal coordination of multiple physiological and behavioural processes that are necessary for homeostasis. In the skeleton, it has long been known that metabolic functions of chondrocytes, osteoblasts and osteoclasts exhibit intrinsic circadian rhythms. In addition, results from animal models reveal a close connection between the disruption of circadian rhythms and skeletal disorders such as rheumatoid arthritis, osteoarthritis and osteoporosis. In this review, we summarise the latest insights into the genetic and biochemical mechanisms linking cartilage and bone physiology to the circadian clock system. We also discuss how this knowledge can be utilised to improve human health.

Evolution Analysis of the Circadian Clock Protein KaiB

2013 ◽  
Vol 647 ◽  
pp. 391-395
Author(s):  
Liu Sen ◽  
Song Liu
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Feedback Loop ◽  
Circadian System ◽  
Circadian Rhythmicity ◽  
Physiological Functions ◽  
Clock System ◽  
Evolution Analysis ◽  
Clock Protein

Regulation of daily physiological functions with approximate a 24-hour periodicity, or circadian rhythms, is a characteristic of eukaryotes. So far, cyanobacteria are only known prokaryotes reported to possess circadian rhythmicity. The circadian system in cyanobacteria comprises both a post-translational oscillator (PTO) and a transcriptional/translational feedback loop (TTFL). The PTO can be reconstituted in vitro with three purified proteins (KaiA, KaiB, and KaiC) with the existence of ATP. Phase of the nanoclockwork has been associated with the phosphorylation states of KaiC, with KaiA promoting the phosphorylation of KaiC, and KaiB de-phosphorylating KaiC. Here we studied the evolution of the KaiB protein. The result will be helpful in understanding the evolution of the circadian clock system.

The role of disturbed circadian clocks in the development of depression-like behavior and metabolic comorbidity in mice

2017 ◽  
Vol 41 (S1) ◽  
pp. S531-S531 ◽  
Author(s):  
D. Landgraf ◽  
R. Barandas ◽  
J.E. Long ◽  
C.D. Proulx ◽  
M.J. McCarthy ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Learned Helplessness ◽  
Viral Vectors ◽  
Metabolic Diseases ◽  
Central Element ◽  
Tail Suspension Test ◽  
Circadian Clocks ◽  
Metabolic Functions ◽  
Response To Stress ◽  
Competing Interest

Major depressive disorder (MDD) is often associated with disturbed circadian rhythms. However, a definitive causal role for functioning circadian clocks in mood regulation has not been established. We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). In these SCN-specific Bmal1-knockdown (SCN-Bmal1-KD) mice, circadian rhythms were greatly attenuated in the SCN. In the learned helplessness paradigm, the SCN-Bmal1-KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN-Bmal1-KD mice also showed an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Furthermore, they displayed greater weight gain, which is frequently observed in MDD patients. Since the circadian system controls important brain systems that regulate affective, cognitive, and metabolic functions, and neuropsychiatric and metabolic diseases are often correlated with disturbances of circadian rhythms, we hypothesize that dysregulation of circadian clocks plays a central role in metabolic comorbidity in psychiatric disorders. In fact, circadian rhythm disturbances have been linked to individual psychiatric and metabolic disorders, but circadian aspects of such disorders have not been considered previously in an integrated manner. Treating and preventing disturbances of circadian clocks in patients suffering psychiatric and metabolic symptoms may be a central element for therapies targeting both disorders concurrently.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Depression

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Roberto Salgado-Delgado ◽  
Araceli Tapia Osorio ◽  
Nadia Saderi ◽  
Carolina Escobar
Keyword(s):  
Circadian Rhythms ◽  
Biological Clock ◽  
Therapeutic Strategies ◽  
Circadian System ◽  
Metabolic Functions ◽  
Lighting Conditions ◽  
Wide Range ◽  
Close Relationship ◽  
And Behavior ◽  
Depressive States

Circadian factors might play a crucial role in the etiology of depression. It has been demonstrated that the disruption of circadian rhythms by lighting conditions and lifestyle predisposes individuals to a wide range of mood disorders, including impulsivity, mania and depression. Also, associated with depression, there is the impairment of circadian rhythmicity of behavioral, endocrine, and metabolic functions. Inspite of this close relationship between both processes, the complex relationship between the biological clock and the incidence of depressive symptoms is far from being understood. The efficiency and the timing of treatments based on chronotherapy (e.g., light treatment, sleep deprivation, and scheduled medication) indicate that the circadian system is an essential target in the therapy of depression. The aim of the present review is to analyze the biological and clinical data that link depression with the disruption of circadian rhythms, emphasizing the contribution of circadian desynchrony. Therefore, we examine the conditions that may lead to circadian disruption of physiology and behavior as described in depressive states, and, according to this approach, we discuss therapeutic strategies aimed at treating the circadian system and depression.

Circadian Rhythms of Endothelial Nitric Oxide Synthase and Toll-like Receptors 2 Production in Females with Rheumatoid Arthritis Depending on NOS3 Gene Polymorphism

2020 ◽  
Vol 15 (2) ◽  
pp. 145-151
Author(s):  
Kateryna Zaichko ◽  
Nataliia Zaichko ◽  
Oleksandr Maievskyi ◽  
Oleksandr Korotkyi ◽  
Tetyana Falalyeyeva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Circadian Rhythms ◽  
Gene Polymorphism ◽  
Endothelial Nitric Oxide Synthase ◽  
Toll Like Receptors ◽  
Nos3 Gene ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Background: Rheumatoid Arthritis (RA) is an autoimmune polygenic disease characterized by rapid disability progression and high prevalence. Progression of RA is closely associated with chronobiological changes in the production of some hormones and inflammatory mediators, influencing the disease course and therapy efficacy. The main pathogenetic mechanism of RA is angiogenesis, which is controlled by biological clock-genes. Further investigation of circadian rhythms of angiogenic mediators production in RA patients may be considered as important and relevant. The aim of this study was to establish daily variability of serum endothelial Nitric Oxide Synthase (NOS3) and toll-like receptors 2 (sTLR2) levels in female RA patients depending on the NOS3 gene polymorphism. Methods: We examined 173 RA patients (100% female) aged 43.7 ± 7.35 years and 34 age-matched healthy women without joint diseases and autoimmune diseases (control). RA was diagnosed by ACR/EULAR 2010 criteria. Blood serum NOS3 and sTLR2 levels were determined at 08:00 and 20:00 using Cloud-Clone Corp kits (USA). NOS3 T-786С (rs2070744) polymorphism was determined by Real-Time PCR (Bio-Rad iCycler IQ5) using SNP-express kits. The SPSS22 software package was used for statistical processing of the results. Results: Females with RA demonstrated oppositely directed serum NOS3 and sTLR2 daily changes: NOS3 level in the morning (08:00) was lower than in the evening (+ 45.5 ± 30.7%), and sTLR2 level in the evening (at 20:00) was lower than in the morning (-21.6 ± 13.1%). RA patients had differences in NOS3 and sTLR2 production depending on NOS3 T786C genotype. CC subjects had NOS3 level at 08:00, 20:00 and day average levels lower (16-25%), and sTLR2 level higher (24-27%) than those of TT subjects. RA patients, carriers of CC genotype, had higher chances of NOS3 and sTLR2 aberrant production compared to TT and TC genotype carriers (OR = 2.99 and 4.79, respectively). Conclusion: RA patients demonstrated oppositely directed circadian changes of serum NOS3 and sTLR2. CC genotype carriers had lower NOS3 and higher sTLR2 production rates than TT and TC genotype carriers.

Disrupted circadian rhythms in VIP- and PHI-deficient mice

2003 ◽  
Vol 285 (5) ◽  
pp. R939-R949 ◽  
Author(s):  
Christopher S. Colwell ◽  
Stephan Michel ◽  
Jason Itri ◽  
Williams Rodriguez ◽  
J. Tam ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Wheel Running ◽  
Activity Rhythm ◽  
Activity Patterns ◽  
Circadian System ◽  
Diurnal Rhythms ◽  
Constant Darkness ◽  
Light Cycle ◽  
Wild Type ◽  
Deficient Mice

The related neuropeptides vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are expressed at high levels in the neurons of the suprachiasmatic nucleus (SCN), but their function in the regulation of circadian rhythms is unknown. To study the role of these peptides on the circadian system in vivo, a new mouse model was developed in which both VIP and PHI genes were disrupted by homologous recombination. In a light-dark cycle, these mice exhibited diurnal rhythms in activity which were largely indistinguishable from wild-type controls. In constant darkness, the VIP/PHI-deficient mice exhibited pronounced abnormalities in their circadian system. The activity patterns started ∼8 h earlier than predicted by the previous light cycle. In addition, lack of VIP/PHI led to a shortened free-running period and a loss of the coherence and precision of the circadian locomotor activity rhythm. In about one-quarter of VIP/PHI mice examined, the wheel-running rhythm became arrhythmic after several weeks in constant darkness. Another striking example of these deficits is seen in the split-activity patterns expressed by the mutant mice when they were exposed to a skeleton photoperiod. In addition, the VIP/PHI-deficient mice exhibited deficits in the response of their circadian system to light. Electrophysiological analysis indicates that VIP enhances inhibitory synaptic transmission within the SCN of wild-type and VIP/PHI-deficient mice. Together, the observations suggest that VIP/PHI peptides are critically involved in both the generation of circadian oscillations as well as the normal synchronization of these rhythms to light.

scholarly journals Genetic interactions between clock mutations in Neurospora crassa : can they help us to understand complexity?

2001 ◽  
Vol 356 (1415) ◽  
pp. 1717-1724 ◽  
Author(s):  
Louis W. Morgan ◽  
Jerry F. Feldman ◽  
Deborah Bell-Pedersen
Keyword(s):  
Coupled Oscillators ◽  
Temperature Compensation ◽  
White Collar ◽  
Circadian System ◽  
Genetic Interactions ◽  
Circadian Clocks ◽  
Metabolic Effects ◽  
Clock Model ◽  
Number Of Genes ◽  
Single Oscillator

Recent work on circadian clocks in Neurospora has primarily focused on the frequency ( frq ) and white–collar ( wc ) loci. However, a number of other genes are known that affect either the period or temperature compensation of the rhythm. These include the period (no relationship to the period gene of Drosophila ) genes and a number of genes that affect cellular metabolism. How these other loci fit into the circadian system is not known, and metabolic effects on the clock are typically not considered in single–oscillator models. Recent evidence has pointed to multiple oscillators in Neurospora , at least one of which is predicted to incorporate metabolic processes. Here, the Neurospora clock–affecting mutations will be reviewed and their genetic interactions discussed in the context of a more complex clock model involving two coupled oscillators: a FRQ/WC–based oscillator and a ‘ frq –less’ oscillator that may involve metabolic components.

scholarly journals The Regulation of Bone Metabolism and Disorders by Wnt Signaling

2019 ◽  
Vol 20 (22) ◽  
pp. 5525 ◽  
Author(s):  
Kazuhiro Maeda ◽  
Yasuhiro Kobayashi ◽  
Masanori Koide ◽  
Shunsuke Uehara ◽  
Masanori Okamoto ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Wnt Signaling ◽  
Bone Metabolism ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Osteoporosis Treatment ◽  
Biological Phenomena ◽  
Approximate Molecular Weight ◽  
Skeletal Disorders ◽  
Canonical Wnt

Wnt, a secreted glycoprotein, has an approximate molecular weight of 40 kDa, and it is a cytokine involved in various biological phenomena including ontogeny, morphogenesis, carcinogenesis, and maintenance of stem cells. The Wnt signaling pathway can be classified into two main pathways: canonical and non-canonical. Of these, the canonical Wnt signaling pathway promotes osteogenesis. Sclerostin produced by osteocytes is an inhibitor of this pathway, thereby inhibiting osteogenesis. Recently, osteoporosis treatment using an anti-sclerostin therapy has been introduced. In this review, the basics of Wnt signaling, its role in bone metabolism and its involvement in skeletal disorders have been covered. Furthermore, the clinical significance and future scopes of Wnt signaling in osteoporosis, osteoarthritis, rheumatoid arthritis and neoplasia are discussed.

Light-induced suppression of the rat circadian system

1995 ◽  
Vol 268 (5) ◽  
pp. R1111-R1116 ◽  
Author(s):  
P. Depres-Brummer ◽  
F. Levi ◽  
G. Metzger ◽  
Y. Touitou
Keyword(s):  
Locomotor Activity ◽  
Body Temperature ◽  
Circadian Rhythms ◽  
Prolonged Exposure ◽  
Light Exposure ◽  
Continuous Light ◽  
Circadian System ◽  
Short Exposure ◽  
Complete Suppression ◽  
Continuous Darkness

In a constant environment, circadian rhythms persist with slightly altered period lengths. Results of studies with continuous light exposure are less clear, because of short exposure durations and single-variable monitoring. This study sought to characterize properties of the oscillator(s) controlling the rat's circadian system by monitoring both body temperature and locomotor activity. We observed that prolonged exposure of male Sprague-Dawley rats to continuous light (LL) systematically induced complete suppression of body temperature and locomotor activity circadian rhythms and their replacement by ultradian rhythms. This was preceded by a transient loss of coupling between both functions. Continuous darkness (DD) restored circadian synchronization of temperature and activity circadian rhythms within 1 wk. The absence of circadian rhythms in LL coincided with a mean sixfold decrease in plasma melatonin and a marked dampening but no abolition of its circadian rhythmicity. Restoration of temperature and activity circadian rhythms in DD was associated with normalization of melatonin rhythm. These results demonstrated a transient internal desynchronization of two simultaneously monitored functions in the rat and suggested the existence of two or more circadian oscillators. Such a hypothesis was further strengthened by the observation of a circadian rhythm in melatonin, despite complete suppression of body temperature and locomotor activity rhythms. This rat model should be useful for investigating the physiology of the circadian timing system as well as to identify agents and schedules having specific pharmacological actions on this system.

scholarly journals Interaction between photoperiod and variation in circadian rhythms in tomato

2022 ◽  
Author(s):  
Yanli Xiang ◽  
Thomas Sapir ◽  
Pauline Rouillard ◽  
Marina Ferrand ◽  
Jose M Jimenez-Gomez
Keyword(s):  
Seasonal Variation ◽  
Circadian Rhythms ◽  
Phase Shift ◽  
Circadian Clock ◽  
Environmental Changes ◽  
Circadian Clocks ◽  
Biological Processes ◽  
Near Isogenic Lines ◽  
Transcriptomic Profiling ◽  
Isogenic Lines

Many biological processes follow circadian rhythmicity and are controlled by the circadian clock. Predictable environmental changes such as seasonal variation in photoperiod can modulate circadian rhythms, allowing organisms to adjust to the time of the year. Modification of circadian clocks is especially relevant in crops to enhance their cultivability in specific regions by changing their sensibility to photoperiod. In tomato, the appearance of mutations in EMPFINDLICHER IM DUNKELROTEN LICHT 1 (EID1, Solyc09g075080) and NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED GENE 2 (LNK2, Solyc01g068560) during domestication delayed its circadian rhythms, and allowed its expansion outside its equatorial origin. Here we study how variation in circadian rhythms in tomato affects its perception of photoperiod. To do this, we create near isogenic lines carrying combinations of wild alleles of EID1 and LNK2 and perform transcriptomic profiling under two different photoperiods. We observe that EID1, but not LNK2, has a large effect on the tomato transcriptome and its response to photoperiod. This large effect of EID1 is likely a consequence of the global phase shift elicited by this gene in tomato's circadian rhythms.

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