TGF beta 1 and biglycan, decorin, and fibromodulin metabolism in canine cartilage

TGF beta 1 and biglycan, decorin, and fibromodulin metabolism in canine cartilage
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DOI:
10.1053/s1063-4584(02)00349-7
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发表时间:
2003-03-01
影响因子:
7
通讯作者:
Roughley, PJ
Roughley, PJ
中科院分区:
医学2区
文献类型:
--
作者:
Burton-Wurster, N;Liu, W;Roughley, PJ

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目的:小分子蛋白多糖(PGs)在晚期骨关节炎中可能积聚,即使蛋白多糖丢失也是如此。目前尚不清楚转化生长因子(TGF)β在这种积累中起什么作用。我们的目标是研究转化生长因子β1对软骨外植体中核心蛋白聚糖、双聚糖和纤维调素的合成和积累的调控能力。设计:关节软骨在含或不含转化生长因子β1的条件下培养16天。结果:培养16d后,(SO4)-S-35-小PGs的合成增加,而对照组的合成减少。16天后,转化生长因子β1组和对照组的(SO4)-S-35-核心蛋白聚糖的差异达到9倍,而内源性核心蛋白聚糖总量的差异不到1.5倍。(SO_4)-S-35-核心蛋白聚糖在经转化生长因子β1处理的培养物中具有相同的核心蛋白,但糖胺多糖链比对照细胞中的核心蛋白的糖胺聚糖链更长。在内源性双聚糖中没有检测到明显的差异,但转化生长因子β1外植体中纤维调制蛋白的积累平均是对照组的3.8倍。结论:转化生长因子β1对三种小前列腺素的堆积有不同程度的影响,其中以纤维调素含量增加最为迅速。(C)2003国际骨性关节炎研究会。爱思唯尔科学有限公司出版。版权所有。
Objective: Small proteoglycans (PGs) may accumulate in late stage osteoarthritis even as aggrecan is lost. It is not clear what role transforming growth factor (TGF) beta has in this accumulation. Our goal was to investigate the ability of TGF beta 1 to modulate the synthesis and accumulation of decorin, biglycan, and fibromodulin in cartilage explants cultured under conditions in which aggrecan synthesis remains relatively constant.Design: Articular cartilage was cultured in the presence or absence of 4 ng/ml TGF beta 1 for up to 16 days. Material extracted from cartilage was assayed for (SO4)-S-35-large and small PGs and for total endogenous decorin, biglycan and fibromodulin.Results: The synthesis of (SO4)-S-35 small PGs increased during the 16 days in culture in response to TGF beta 1, but declined in control cultures. The difference in (SO4)-S-35-decorin between TGF beta 1 and control samples reached nine-fold after 16 days, while the difference in total endogenous decorin was less than 1.5-fold. (SO4)-S-35-decorin, which was present in TGF beta 1-treated cultures had an identical core protein, but a longer glycosaminoglycan chain than that of decorin in control cultures. No significant differences in endogenous biglycan were detected, but accumulation of fibromodulin in TGF beta 1 explants exceeded fibromodulin in controls, on average, by 3.8-fold. Fibromodulin was present in cartilage in both keratan sulfate- and non-sulfated oligosaccharide-substituted forms.Conclusions: The accumulation of each of the three small PGs was affected to a different extent in response to TGF beta 1. Of the three, fibromodulin content was most rapidly augmented in response to TGF beta 1. (C) 2003 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.