Inflammatory cytokines, which induce articular chondrocytes to undergo hypertrophic transformation and apoptotic death, mediate osteoarthritis (OA) progression. L-Lysine (Lys) are involved in multiple biological processes including inflammatory regulation. However, rare research has addressed the effects of Lys on human chondrocytes. In this study, chondrocytes were isolated from articular cartilage of OA patients, stimulated with interleukin-1 beta (IL-1 beta) and subsequently supplied with Lys. Lys improved hypertrophic transformation of chondrocytes. However, the proliferation of IL-1 beta-stimulated chondrocytes was still faster than that of unstimulated cells even under providing Lys supplement. The mRNA levels of tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-9 (MMP-9) decreased when normal chondrocytes treated with Lys. IL-1 beta stimulation upregulated type I collagen, type X collagen, IL-1 beta, TNF-alpha, MMP-3, MMP-9 and downregulated aggrecan, type II collagen mRNA levels. On the contrary, Lys downregulated TNF-alpha, MMP-3 levels, restored aggrecan and collagens expressions, and further increased the aggrecan/type I collagen and type II collagen/type I collagen rations in 1L-1 beta-stimulated chondrocytes. In addition, Lys treatment decreased the protein productions of TNF-alpha and MMP-3 in stimulated cells. Our results suggest that Lys may modulate matrix proteins, inflammatory and catabolic cytokines in OA chondrocytes. (C) 2016 Elsevier Ltd. All rights reserved.