Abstract
The etiology of osteoarthritis (OA) is multifactorial, with no effective disease-modifying-drugs. L-theanine has been reported to inhibit inflammatory responses in some diseases and this study aimed to investigate the effect of L-theanine on Interleukin-1(IL-1)β-stimulated chondrocytes, and in an injury-induced OA rat model. Primary chondrocytes were stimulated by IL-1β (10 ng/mL) for 24 h and then co-cultured with L-theanine for 24 h. The effects of L-theanine on IL-1β-stimulated expression of pro-inflammatory cytokines and hydrolytic enzyme were analyzed using Western blotting, quantitative polymerase chain reaction (q-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. An immunofluorescence assay was used to detect nuclear factor kappa B (NF-κB) phosphorylation. OA was induced by anterior cruciate ligament transection (ACLT) surgery in rats and celecoxib was used as a positive control. OA severity was measured using the Osteoarthritis Research Society International (OARSI) grading system to describe histological changes. The results showed that L-theanine decreased the expression of pro-inflammatory mediators, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), both in vivo and in vitro. L-theanine treatment inhibited IL-1β-induced upregulation of matrix metalloproteinases (MMP)-3 and MMP-13, as well as inhibited NF-κB p65 activation. In vivo animal model showed that L-theanine administration (200 mg/kg) significantly alleviated OA lesions and decreased OARSI score. Our data indicated that L-theanine decreased inflammatory cytokines and protected extracellular matrix degradation through inhibition of the NF-κB pathway, and L-theanine may be considered a promising therapeutic strategy in OA prevention.
Highlights
Low-grade inflammation plays an important role in osteoarthritis (OA) [1,2], and pre-clinical and clinical trials support therapeutic targets for inflammation in OA treatment
L-theanine treatment alone resulted in no demonstrable adverse effects on cell viability, which was in accordance with the results of the cell counting kit (CCK)-8 assay
The results showed that significantly increased serum levels of COX-2 and PGE-2, and highly increased levels of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) were observed in rats that underwent anterior cruciate ligament transection (ACLT) surgery without L-theanine treatment
Summary
Low-grade inflammation plays an important role in osteoarthritis (OA) [1,2], and pre-clinical and clinical trials support therapeutic targets for inflammation in OA treatment. Inflammation cytokines such as cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE-2) that cause an increase in OA pain. The dysfunction and metabolic disorders of chondrocytes and ECM may cause pathological changes to articular cartilage [8]. These factors are locally secreted by chondrocytes, synovial cells, and macrophagocytes, and aggravate cartilage damage through receptors on the cell surface and crosstalk between signaling pathway
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have