The effect of taurine on death pathways causing chondrocyte degeneration in osteoarthritis

Osteoarthritis (OA) is a chronic, progressive joint disease that affects over 250 million people worldwide and is particularly prevalent among the elderly population. Due to its significant contribution to morbidity and reduced quality of life, OA leads to healthcare expenditures exceeding 2% of the gross national product in developed countries. Consequently, research into new and effective approaches for OA treatment has garnered considerable interest. Recent studies indicate that the degeneration of joint cartilage and chronic inflammation are key factors in OA pathogenesis. Joint cartilage is composed of the extracellular matrix (ECM) and chondrocytes. Chondrocytes, the only cell type in joint cartilage, are considered target cells in OA treatment because they are responsible for maintaining healthy cartilage structure and joint mobility. Cell death is morphologically categorized into three main types: apoptosis, autophagic cell death, and necrosis/necroptosis. A clear understanding of the interplay between these three cell death pathways could be a significant step in OA treatment. Taurine, a semi-essential β-amino acid, is found in high concentrations in excitable tissues and has various physiological functions in mammals. Its most notable feature, which has attracted researchers' attention, is its cytoprotective effects. However, there are limited studies on the effects of taurine on OA. The aim of this study is to demonstrate the effects of taurine on OA pathogenesis and its relationship with autophagy/apoptosis/necroptosis. Healthy and osteoarthritic chondrocytes were cultured from patients diagnosed with stage 3 OA according to the Kellgren-Lawrence Classification and who underwent total knee replacement surgery. Experimental groups were established using taurine, the apoptosis inhibitor Z-vAD, and the necroptosis inhibitor necrostatin-1 (Nec-1), with appropriate doses and durations determined. Reverse transcription quantitative real-time PCR (RT-qPCR) was used to detect the expression of autophagy markers Bcl-2 interacting protein 1 (Beclin 1) and p62 (SQSTM1, Sequestosome-1), necroptosis marker Receptor-interacting serine/threonine-protein kinase 3 (RIP3), apoptosis markers Bcl-2-associated X protein (Bax) and B-cell leukemia/lymphoma 2 protein (Bcl-2), and the chondrocyte structural gene aggrecan. Western blot analysis was performed to assess the expression of chondrocyte marker Collagen 2, autophagy markers Light chain 3 I/II (LC3I/II), p62, and Bcl-2 interacting protein 1 (Beclin 1), as well as apoptosis markers Caspase 3 and Poly [ADP-ribose] polymerase 1 (Parp1). When taurine was combined with necrostatin-1, it showed cell viability-enhancing effects. RT-qPCR analyses revealed that this group had higher levels of aggrecan. Collagen 2 measurements also indicated the highest levels in this group. These findings suggest that necroptosis inhibition may have potential protective effects on cartilage metabolism. Overall, these results suggest that the combination of taurine and necrostatin-1 could be a promising approach in OA treatment.