期刊
BIOCHEMICAL PHARMACOLOGY
卷 82, 期 12, 页码 1919-1929出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2011.09.009
关键词
IL-1 beta; TGF beta 1; Micromasses; Anti-inflammatory drugs; Naproxen; Prednisolone
资金
- UCB (Slough, United Kingdom)
- William Harvey Research Foundation (London, United Kingdom)
- National Institutes of Health [R01-AG022021]
Osteoarthritis is a highly prevalent and disabling disease for which we do not have a cure. The identification of suitable molecular targets is hindered by the lack of standardized, reproducible and convenient screening assays. Following extensive comparisons of a number of chondrocytic cell lines, culture conditions, and readouts, we have optimized an assay utilizing C-28/I2, a chondrocytic cell line cultured in high-density micromasses. Utilizing molecules with known effects on cartilage (e.g. IL-1 beta, TGF beta 1, BMP-2), we have exploited this improved protocol to (i) evoke responses characteristic of primary chondrocytes; (ii) assess the pharmacodynamics of gene over-expression using non-viral expression vectors; (iii) establish the response profiles of known pharmacological treatments; and (iv) investigate their mechanisms of action. These data indicate that we have established a medium-throughput methodology for studying chondrocyte-specific cellular and molecular responses (from gene expression to rapid quantitative measurement of sulfated glycosaminoglycans by Alcian blue staining) that may enable the discovery of novel therapeutics for pharmacological modulation of chondrocyte activation in osteoarthritis. (C) 2011 Elsevier Inc. All rights reserved.
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