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.

Melatonin Prevents Chondrocyte Matrix Degradation in Rats with Experimentally Induced Osteoarthritis by Inhibiting Nuclear Factor-κB via SIRT1

“…Melatonin is an important hormone involved in the regulation of circadian rhythms, and several studies have shown that a decrease in systemic levels of melatonin can lead to circadian rhythm disorders [ 36 , 37 ]. In addition, circadian rhythm disorders are one of the causes of osteoarthritis, depression and many other diseases [ 38 , 39 , 40 ]. Here, we investigated the protective effect of melatonin on cartilage.…”

Study on the efficacy and mechanism of Jintiange Capsules in the tre atment of osteoarthritis in rats

“…IL-1β is also the main reason for the induction of OA 15,16 . Research data show that TGF-β1 participates in the synthesis of type II collagen and downregulates MMP 17 . The results showed that JTG can achieve an anti-in ammatory effect and reduce in ammatory response by promoting the expression of TGF-β1 in serum and inhibiting the expression of IL-1β.…”

Targeting Cartilage miR-195/497 Cluster for Osteoarthritis Treatment Regulates the Circadian Clock

“…Hence, we validated the expression of Per2. To further investigate the downstream and upstream targets that miR-195/497-5p affects through the ERK/CREB pathway, we focus on the pathogenesis mechanism of the circadian rhythm of OA cartilage based on our previous study and the results of meta-analysis [31]. Subsequently, target genes and downstream pathways regulated by miR-195-5p and miR-497-5p were identified using the ENCORI database [32].…”