03 March 2020 : Animal Research
Promotion of G1/S Transition and Inhibition of Inflammatory Cytokine Production by Hydroxypyridinone-Coumarin in Osteoarthritis Rats
Kai Yang1BCD, Gang Chen2BCD, Xiongxun Wang3ADEF*DOI: 10.12659/MSM.920784
Med Sci Monit 2020; 26:e920784
Abstract
BACKGROUND: Osteoarthritis is a joint disorder characterized by articular cartilage degradation leading to joint stiffness and pain. The present study investigated the effect of hydroxypyridinone-coumarin on proliferation of chondrocytes.
MATERIAL AND METHODS: Chondrocyte proliferation was assessed by MTT assay, and distribution of cells in various phases of the cell cycle was determined using flow cytometry. RT-PCR and Western blot assays were used for assessment of mRNA and protein levels, respectively. Osteoarthritis was induced in the rats by injecting monosodium iodoacetate (5 mg/kg) by the intra-articular route. The rats in the treatment groups were intraperitoneally injected with 5, 10, or 15 mg/kg doses of hydroxypyridinone-coumarin alternately for 1 month.
RESULTS: The proliferation of chondrocytes was increased significantly (P<0.05) by treatment with hydroxypyridinone-coumarin in a concentration-based manner. The increase in chondrocyte proliferation by hydroxypyridinone-coumarin was maximum at 50 µM. Treatment with hydroxypyridinone-coumarin markedly increased chondrocyte population in S and G2/M phases, with subsequent reduction in G0/G1 phase. The cyclin D1, CDK4, and CDK6 levels in the chondrocytes were increased by treatment with hydroxypyridinone-coumarin. The production of IL-6, TNF-α, and IL-1β in the osteoarthritis rats was markedly suppressed by hydroxypyridinone-coumarin. Treatment of the OA rats with hydroxypyridinone-coumarin markedly reduced the expression of IκB-α and NF-κB p65.
CONCLUSIONS: The present study revealed that the proliferative potential of chondrocytes is increased by hydroxypyridinone-coumarin through acceleration of G1/S transition. Moreover, hydroxypyridinone-coumarin treatment reduced inflammatory cytokine production in the osteoarthritis rats. Therefore, hydroxypyridinone-coumarin should be evaluated further for possible use in the treatment of osteoarthritis.
Keywords: Anti-Inflammatory Agents, Chondrocytes, Cytokines, Cartilage, Articular, Coumarins, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, G1 Phase Cell Cycle Checkpoints, Interleukins, NF-KappaB Inhibitor alpha, Osteoarthritis
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
06 Mar 2024 : Clinical Research
Comparison of Outcomes between Single-Level and Double-Level Corpectomy in Thoracolumbar Reconstruction: A ...Med Sci Monit In Press; DOI: 10.12659/MSM.943797
21 Mar 2024 : Meta-Analysis
Economic Evaluation of COVID-19 Screening Tests and Surveillance Strategies in Low-Income, Middle-Income, a...Med Sci Monit In Press; DOI: 10.12659/MSM.943863
10 Apr 2024 : Clinical Research
Predicting Acute Cardiovascular Complications in COVID-19: Insights from a Specialized Cardiac Referral Dep...Med Sci Monit In Press; DOI: 10.12659/MSM.942612
06 Mar 2024 : Clinical Research
Enhanced Surgical Outcomes of Popliteal Cyst Excision: A Retrospective Study Comparing Arthroscopic Debride...Med Sci Monit In Press; DOI: 10.12659/MSM.941102
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952