YKL-40 (cartilage gp-39) induces proliferative events in cultured chondrocytes and synoviocytes and increases glycosaminoglycan synthesis in chondrocytes

YKL-40 (cartilage gp-39), is a mammalian glycoprotein related in sequence t o chitinases. Its function is unknown, but it is thought to be involved in tissue remodeling. Immunocytochemical staining of YKL-40 in guinea pig chon drocytes (GPC), rabbit chondrocytes (RC), and rabbit synoviocytes (RS) was higher in dividing cells than in confluent cells, suggesting a participatio n of YKL-40 in cell cycle events. As assessed by the MITT assay, YKL-40 at 1.9-7.6 nM had dose-dependent mitogenic activity toward the three cell type s. At 7.6 nM, YKL-40 increased the number of cells of 42% in GPC, 75% in RC , and 86% in RS after 72 h. YKL-40 also stimulated total proteoglycan synth esis by chondrocytes in a dose-dependent manner as assessed by Na[(SO4)-S-3 5] incorporation and cetylpyridinium chloride precipitation. At 9.4 nM, YKL -40 increased proteoglycan synthesis of 42% in GPC and 58% in RC after 24 h . The growth factor properties of YKL-40 may explain the increased tissue r emodeling associated with high levels of YKL-40 in joint diseases, and poss ibly, in malignant pathologies such as breast cancer or colorectal cancer. (C) 2001 Academic Press.