期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 283, 期 5, 页码 1118-1123出版社
ACADEMIC PRESS INC
DOI: 10.1006/bbrc.2001.4911
关键词
cholecyctokinin-B/gastrin receptor antagonist; chondrocyte; articular cartilage; proliferation; chondroitin sulfate; collagen gel culture
A newly synthesized compound, AG-041R, 3R-1-(2,2Diethoxyethyl)-3- ((4methylphenyl) amino-carbonylmethyl)-3-( (4methylphenyl)ureido-indoline-2-one), is a cholecyctokinin-B/gastrin receptor antagonist, but unexpectedly magnified cartilage formation in vivo, Indeed, AG-041R is a potentially effective reagent for the repair of articular cartilage defects. To clarify its effects on chondrocytes, we studied the proliferation, matrix formation, and gene expression of rabbit primary chondrocytes cultured in type I collagen gel composites with AG-041R, Both proliferation and glycosaminoglycan synthesis were stimulated with 1 muM AG-041R, but suppressed with 10 muM. The ratio of the amounts of two chondroitin sulfate isomers, chondroitin-6-sulfate to chondroitin-4-sulfate tan indicator of cartilage maturation), increased with 1 muM but decreased with 10 muM AG-041R, Gene expression analysis showed there was no change in the relative expression levels of chondrocyte markers, Type II collagen and Aggrecan, and osteoblast and adipocyte markers, Type I collagen and PPAR gamma, respectively. These findings suggest that adequate concentrations of AG-041R stimulate proliferation of chondrocytes in the matrix, without changing their differentiated characteristics. (C) 2001 Academic Press.
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