Melatonin Attenuates the Progression of Osteoarthritis in Rats by Inhibiting Inflammation and Related Oxidative Stress on the Surface of Knee Cartilage

Abstract

Objective To investigate the correlation between melatonin and osteoarthritis (OA) in rats. To explore the relevant mechanisms in the occurrence and development of osteoarthritis in rats, and to further understand the disease of osteoarthritis. Methods Forty healthy 6‐month‐old male SD rats were randomly divided into two groups: sham and drug intervention groups. Pre‐OA modeling, enzyme‐linked immunosorbent assay was employed to detect the levels of IL‐1β, IL‐6, COX‐2, and melatonin in the serum of the rats in each group. For OA modeling, we administered an injection of papain into the knee cavity of all rats. The levels of IL‐1β, IL‐6, and COX‐2 in the serum of rats in each group were detected 2 weeks after the modeling. Additionally, 2 weeks after the modeling, the rats in the drug intervention group were intraperitoneally injected with melatonin antagonists. The rats in the sham group were intraperitoneally injected with normal saline for 2 weeks. The levels of IL‐1β, IL‐6, and COX‐2 in the serum of each group were measured at the second, third, and fourth weeks after the drug intervention, and the levels of melatonin in the serum were measured at the second week after the drug intervention. Finally, the rats were euthanized by cervical dislocation, and pathological sections were collected from the knee joint to observe the pathological tissue changes under a microscope, and Mankin score was determined. The independent samples t‐test method was used for analysis. Results The imaging examination after the drug intervention showed that the modeling of knee osteoarthritis in rats was successful. In the pathological findings, HE staining showed a legible cartilage structure of each layer, with cartilage proliferation and partial cartilage tearing to the radial layer. The tide line was intact; toluidine blue staining revealed more obvious changes. The differences among the mean values of IL‐6, IL‐1β, and COX‐2 measured in each period were statistically significant (t = 5.50, p < 0.05). The measured mean values of IL‐6, IL‐1β, and COX‐2 revealed statistically significant differences among the groups (t = 2.01, p < 0.05). The intergroup comparison of the Mankin scores in each period showed statistically significant differences. Conclusion Melatonin may inhibit inflammation and associated oxidative stress on the surface of knee cartilage. It may be related to the repair and regeneration of articular surface cartilage during the development of OA in the rat knee joint.

Mechanistic study of Huangqi Guizhi Wuwu decoction in the treatment of osteoarthritis using a weighted gene co-expression network and molecular docking techniques

“…IL-6 is closely related to cartilage matrix degeneration and synovial in ammation in OA development; through receptor binding, it can promote the formation of osteoclasts, and serum IL-6 level is positively correlated with the degree of cartilage damage. Studies have shown that IL-6 messenger RNA (mRNA) expression in synovial cells of patients with early knee OA is increased, which is consistent with the results of this study [12]. JUN is composed of c-Fos, c-Jun and other factors and can regulate the release of in ammatory substances, such as IL-8 and TNF, through the MAPK and PI3K/Akt signalling pathways, thus aggravating cartilage degeneration [13,14].…”

Three‐dimensional printed biomimetic multilayer scaffolds coordinated with sleep‐related small extracellular vesicles: A strategy for extracellular matrix homeostasis and macrophage polarization to enhance osteochondral regeneration

“…In addition, MT preserves the proliferation and differentiation properties of BMSCs, enhancing their therapeutic effect. 64 In our previous study, we found that MT increased the expression of circRNA3503 and isolated circRNA3503-loaded sEV, which alleviated apoptosis and maintained the balance between synthesis and degradation of ECM. 30 Herein, we obtained sleep-related sEV by combining MT with sEV, and demonstrated that they simulate endogenous tissue repair mechanisms.…”

“…MT may inhibit inflammation and oxidative stress in cartilage to retard osteoarthritis progression and stimulate cartilage regeneration. In addition, MT preserves the proliferation and differentiation properties of BMSCs, enhancing their therapeutic effect 64 . In our previous study, we found that MT increased the expression of circRNA3503 and isolated circRNA3503‐loaded sEV, which alleviated apoptosis and maintained the balance between synthesis and degradation of ECM 30 .…”

Cannabidiol‐Loaded Poly Lactic‐Co‐Glycolic Acid Nanoparticles with Improved Bioavailability as a Potential for Osteoarthritis Therapeutic

“…Study has revealed that CBD can stimulate matrix synthesis by restoring glycosaminoglycan synthesis [46] . Histological examination using Mankin scoring showed that intra‐articular injection of LPS in rat knee joints induced cartilage structural changes, matrix degradation, and chondrocyte disorganization [47,48] . What's more, MMP‐13, a key enzyme of cartilage matrix degradation in osteoarthritis, expression was also inhibited.…”