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 to chitinases. Its function is unknown, but it is thought to be involved in tissue remodeling. Immunocytochemical staining of YKL-40 in guinea pig chondrocytes (GPC), rabbit chondrocytes (RC), and rabbit synoviocytes (RS) was higher in dividing cells than in confluent cells, suggesting a participation of YKL-40 in cell cycle events. As assessed by the MTT assay, YKL-40 at 1.9-7.6 nM had dose-dependent mitogenic activity toward the three cell types. 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 synthesis by chondrocytes in a dose-dependent manner as assessed by Na[35SO4] 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 remodeling associated with high levels of YKL-40 in joint diseases, and possibly, in malignant pathologies such as breast cancer or colorectal cancer.
De Ceuninck
F
F
Division of Rheumatology, Institut de Recherches Servier, 11 rue des Moulineaux, Suresnes, 92150, France. frderic.deceuninck@fr.netgrs.com
Gaufillier
S
S
Bonnaud
A
A
Sabatini
M
M
Lesur
C
C
Pastoureau
P
P
D054392:Adipokines; D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D000071451:Chitinase-3-Like Protein 1; D019902:Chondrocytes / Q000187:drug effects*; D005269:Femur / Q000166:cytology; D006023:Glycoproteins / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006133:Growth Substances / Q000494:pharmacology*; D006168:Guinea Pigs; D037102:Lectins; D011817:Rabbits; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*; D013977:Tibia / Q000166:cytology
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D006025:Glycosaminoglycans; D006133:Growth Substances; D037102:Lectins