FIBRONECTIN FRAGMENTS ALTER MATRIX PROTEIN-SYNTHESIS IN CARTILAGE TISSUE-CULTURED IN-VITRO

被引:64
作者
XIE, DL [1 ]
HUI, F [1 ]
HOMANDBERG, GA [1 ]
机构
[1] RUSH PRESBYTERIAN ST LUKES MED CTR,RUSH MED COLL,DEPT BIOCHEM,1653 W CONGRESS PKWY,CHICAGO,IL 60612
关键词
D O I
10.1006/abbi.1993.1568
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We reported earlier that fibronectin fragments (Fn-f) added to bovine articular cartilage cultured in serum-free culture causes marked protease expression with resultant proteoglycan (PG) degradation and release into the culture media. We have further characterized the effects of Fn-f by studies of the effects on proteoglycan, collagen, general protein, and DNA synthesis and reversibility of the cartilage damage. We report here that the most active Fn-f, a 29-kDa amino-terminal Fn-f, when added to a 1 μM concentration, depressed PG and general protein synthesis in cartilage by over 50% within 24 h, as measured by sulfate and methionine/cysteine incorporation, respectively. This same Fn-f decreased PG synthesis throughout the full thickness cartilage section as shown by autoradiography. PG and general protein synthesis were significantly depressed within 24 h by 29-kDa Fn-f concentrations as low as 10 nM. Synthesis rates were effected by 100-fold lower Fn-f concentrations than was induction of proteinases. Removal of the 29-kDa Fn-f allowed a gain to supernormal levels of PG and protein synthesis. Cartilage damaged to the extent of removal of over 50% of the total PG did not replace PG after over 4 weeks in 10% serum-Dulbecco's modified Eagle minimum with or without added TGF-b1 and rIGF-a. These data show that while the effects of Fn-f on elevating protease expression and depressing PG synthesis are reversible, the resultant cartilage damage is apparently irreversible in vitro. Therefore, if Fn-f-mediated cartilage damage occurs as part of cartilage disease processes, the pathologic effects would be quite significant. © 1993 Academic Press, Inc.
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页码:110 / 118
页数:9
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