PMID- 36235621 OWN - NLM STAT- MEDLINE DCOM- 20221017 LR - 20221019 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 14 IP - 19 DP - 2022 Sep 24 TI - Melatonin Prevents Chondrocyte Matrix Degradation in Rats with Experimentally Induced Osteoarthritis by Inhibiting Nuclear Factor-kappaB via SIRT1. LID - 10.3390/nu14193966 [doi] LID - 3966 AB - Osteoarthritis (OA) is a common degenerative joint disease characterized by an imbalance of cartilage extracellular matrix (ECM) breakdown and anabolism. Melatonin (MT) is one of the hormones secreted by the pineal gland of the brain and has anti-inflammatory, antioxidant, and anti-aging functions. To explore the role of MT in rats, we established an OA model in rats by anterior cruciate ligament transection (ACLT). Safranin O-fast green staining showed that intraperitoneal injection of MT (30 mg/kg) could alleviate the degeneration of articular cartilage in ACLT rats. Immunohistochemical (IHC) analysis found that MT could up-regulate the expression levels of collagen type II and Aggrecan and inhibit the expression levels of matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), and ADAM metallopeptidase with thrombospondin type 1 motif 4 (ADAMTS-4) in ACLT rats. To elucidate the mechanism of MT in protecting the ECM in inflammatory factor-induced rat chondrocytes, we conducted in vitro experiments by co-culturing MT with a culture medium. Western blot (WB) showed that MT could promote the expression levels of transforming growth factor-beta 1 (TGF-beta1)/SMAD family member 2 (Smad2) and sirtuin 2-related enzyme 1 (SIRT1) and inhibit the expression of levels of phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibi-tor (p-p65) and phosphorylated IkappaB kinase-alpha (p-IkappaBalpha). In addition, WB and real-time PCR (qRT-PCR) results showed that MT could inhibit the expression levels of MMP-3, MMP-13, ADAMTS-4, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in chondrocytes induced by interleukin-1beta (IL-1beta), and up-regulate the expression of chondroprotective protein type II collagen. We found that in vivo, MT treatment protected articular cartilage in the rat ACLT model. In IL-1beta-induced rat chondrocytes, MT could reduce chondrocyte matrix degradation by up-regulating nuclear factor-kB (NF-kappaB) signaling pathway-dependent expression of SIRT1 and protecting chondrocyte by activating the TGF-beta1/Smad2 pathway. FAU - Zhao, Mingchao AU - Zhao M AD - Heilongjiang Key Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. FAU - Song, Xiaopeng AU - Song X AD - Heilongjiang Key Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. FAU - Chen, Hong AU - Chen H AD - Heilongjiang Key Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. FAU - Ma, Tianwen AU - Ma T AD - Heilongjiang Key Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. FAU - Tang, Jilang AU - Tang J AD - Heilongjiang Key Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. FAU - Wang, Xinyu AU - Wang X AD - Heilongjiang Key Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. FAU - Yu, Yue AU - Yu Y AD - Heilongjiang Key Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. FAU - Lv, Liangyu AU - Lv L AD - Heilongjiang Key Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. FAU - Jia, Lina AU - Jia L AD - Heilongjiang Key Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. FAU - Gao, Li AU - Gao L AD - Heilongjiang Key Laboratory Animals and Comparative Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. LA - eng GR - Project No.2017YFD0502200/The National Key Research and Development Program of China/ GR - GA18B203/Applied Technology Research and Development Plan of Heilongjiang/ PT - Journal Article DEP - 20220924 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Aggrecans) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Collagen Type II) RN - 0 (Interleukin-1beta) RN - 0 (NF-kappa B) RN - 0 (Thrombospondins) RN - 0 (Transforming Growth Factor beta1) RN - 139874-52-5 (NF-KappaB Inhibitor alpha) RN - 76057-06-2 (Transforming Growth Factors) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 2.7.11.10 (I-kappa B Kinase) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.5.1.- (Sirt1 protein, rat) RN - EC 3.5.1.- (Sirtuin 1) RN - EC 3.5.1.- (Sirtuin 2) RN - JL5DK93RCL (Melatonin) SB - IM MH - Aggrecans/metabolism MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Antioxidants/metabolism MH - *Cartilage, Articular/metabolism MH - Chondrocytes/metabolism MH - Collagen Type II/metabolism MH - Cyclooxygenase 2/metabolism MH - I-kappa B Kinase/metabolism MH - Interleukin-1beta/metabolism MH - Matrix Metalloproteinase 13/genetics/metabolism MH - Matrix Metalloproteinase 3/metabolism MH - *Melatonin/metabolism MH - NF-KappaB Inhibitor alpha/metabolism MH - NF-kappa B/metabolism MH - Nitric Oxide Synthase Type II/metabolism MH - *Osteoarthritis/drug therapy/metabolism MH - Rats MH - Sirtuin 1/genetics/metabolism MH - Sirtuin 2/metabolism MH - Thrombospondins/metabolism/therapeutic use MH - Transforming Growth Factor beta1/metabolism MH - Transforming Growth Factors/metabolism/therapeutic use PMC - PMC9571821 OTO - NOTNLM OT - NF-kappaB pathway OT - SIRT1 OT - TGF-beta1/Smad2 pathway OT - chondrocytes OT - melatonin COIS- The authors declare no conflict of interest. EDAT- 2022/10/15 06:00 MHDA- 2022/10/18 06:00 PMCR- 2022/09/24 CRDT- 2022/10/14 02:31 PHST- 2022/07/17 00:00 [received] PHST- 2022/09/19 00:00 [revised] PHST- 2022/09/19 00:00 [accepted] PHST- 2022/10/14 02:31 [entrez] PHST- 2022/10/15 06:00 [pubmed] PHST- 2022/10/18 06:00 [medline] PHST- 2022/09/24 00:00 [pmc-release] AID - nu14193966 [pii] AID - nutrients-14-03966 [pii] AID - 10.3390/nu14193966 [doi] PST - epublish SO - Nutrients. 2022 Sep 24;14(19):3966. doi: 10.3390/nu14193966.