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Melatonin Maintains Anabolic-Catabolic Equilibrium and Regulates Circadian Rhythm During Osteoarthritis Development in Animal Models: A Systematic Review and Meta-analysis.

ABSTRACT: Background: The driving force behind osteoarthritis (OA) pathogenesis is an anabolic-catabolic (a/c) imbalance. Melatonin (MT) is a key player in maintaining a/c stability and mitigates OA pathogenesis, but mechanisms underlying its effects remain poorly understood. Objectives: We performed a systematic review analyzing the experimental data that support the clinical applicability of MT in the treatment of OA pathogenesis, placing particular emphasis on the regulation of circadian rhythms and a/c balance. Methods: Major electronic databases and grey literature were used to identify related original articles. Methodological quality of all selected studies was evaluated using the SYRCLE risk of bias tool. Pooled mean differences (MDs)/standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to estimate the effect size. Results: Eleven trials were included in this systematic review. Compared with the control group, MT significantly decreased the levels of interleukin-1β (IL-1β; SMD = -5.45; 95% CI [-6.78, -4.12]; p < 0.00001, and histological grading scale (SMD = -3.46; 95% CI, [-5.24, -1.68]; p < 0.0001). MT significantly increased the transforming growth factor-β1 (TGF-β1; SMD = 1.17; 95% CI [0.31, 2.03]; p < 0.0007). Furthermore, core circadian clock genes Per2 and Cry1 mRNA levels were regulated by MT treatment in OA progression. Conclusion: MT may maintain a/c balance and regulate circadian rhythms during OA development. MT could be used in as adjunct with other interventions to manage pain and OA severity.

SUBMITTER: Sumsuzzman DM

PROVIDER: S-EPMC8484877 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:It is now well established that resistance exercise stimulates muscle protein synthesis and promotes gains in muscle mass and strength. However, considerable variability exists following standardized resistance training programs in the magnitude of muscle cross-sectional area and strength responses from one individual to another. Several studies have recently posited that alterations in satellite cell population, myogenic gene expression and microRNAs may contribute to individual variability in anabolic adaptation. One emerging factor that may also explain the variability in responses to resistance exercise is circadian rhythms and underlying molecular clock signals. The molecular clock is found in most cells within the body, including skeletal muscle, and principally functions to optimize the timing of specific cellular events around a 24 h cycle. Accumulating evidence investigating the skeletal muscle molecular clock indicates that exercise-induced contraction and its timing may regulate gene expression and protein synthesis responses which, over time, can influence and modulate key physiological responses such as muscle hypertrophy and increased strength. Therefore, the circadian clock may play a key role in the heterogeneous anabolic responses with resistance exercise. The central aim of this Hypothesis and Theory is to discuss and propose the potential interplay between the circadian molecular clock and established molecular mechanisms mediating muscle anabolic responses with resistance training. This article begins with a current review of the mechanisms associated with the heterogeneity in muscle anabolism with resistance training before introducing the molecular pathways regulating circadian function in skeletal muscle. Recent work showing members of the core molecular clock system can regulate myogenic and translational signaling pathways is also discussed, forming the basis for a possible role of the circadian clock in the variable anabolic responses with resistance exercise.

Project description:Gut hormones are not only able to regulate digestive, absorptive, and immune mechanisms of the intestine through biological rhythms, but impact the host through their interactions with intestinal microorganisms. Whether hormones in ruminal fluid have an association with the ruminal ecology is unknown. Objectives of the study were to examine relationships between the diurnal change in ruminal hormones and microbiota in lactating cows, and their associations in vivo and in vitro. For the in vivo study, six cows of similar weight (566.8 ± 19.6 kg), parity (3.0 ± 0.0), and milk performance (8,398.7 ± 1,392.9 kg/y) were used. They were adapted to natural light for 2 weeks before sampling and fed twice daily at 07:00 a.m. and 14:00 p.m. Serum, saliva, and ruminal fluid samples were collected at 02:00, 10:00, and 18:00 on the first day and 06:00, 14:00, and 22:00 on the second day of the experimental period. The concentrations of melatonin (MLT), growth hormone (GH), and prolactin (PRL) were measured via radioimmunoassay, whereas amplicon sequencing data were used to analyze relative abundance of microbiota in ruminal fluid. JTK_CYCLE analysis was performed to analyze circadian rhythms of hormone concentrations as well as the relative abundance of microbiota. For the in vitro study, exogenous MLT (9 ng) was added into ruminal fluid incubations to investigate the impacts of MLT on ruminal microbiota. The results not only showed that rumen fluid contains MLT, but the diurnal variation of MLT and the relative abundance of 9% of total rumen bacterial operational taxonomic units (OTUs) follow a circadian rhythm. Although GH and PRL were also detected in ruminal fluid, there was no obvious circadian rhythm in their concentrations. Ruminal MLT was closely associated with Muribaculaceae, Succinivibrionaceae, Veillonellaceae, and Prevotellaceae families in vivo. In vitro, these families were significantly influenced by melatonin treatment, as melatonin treatment increased the relative abundance of families Prevotellaceae, Muribaculaceae while it reduced the relative abundance of Succinivibrionaceae, Veillonellaceae. Collectively, ruminal microbes appear to maintain a circadian rhythm that is associated with the profiles of melatonin. As such, data suggest that secretion of melatonin into the rumen could play a role in host-microbe interactions in ruminants.

Dataset Information

Melatonin Maintains Anabolic-Catabolic Equilibrium and Regulates Circadian Rhythm During Osteoarthritis Development in Animal Models: A Systematic Review and Meta-analysis.

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