Fibronectin-fragment-induced cartilage chondrolysis is associated with release of catabolic cytokines
Fibronectin-fragment-induced cartilage chondrolysis is associated with release of catabolic cytokines
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DOI：
10.1042/bj3210751
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发表时间：
1997-02-01
影响因子：
4.1
通讯作者：
Harris, A
中科院分区：
文献类型：
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作者：
Homandberg, GA;Hui, F;Harris, A
纤维连接蛋白片段对体外培养的关节软骨组织具有分解代谢和合成代谢作用。而1 nM浓度的N-末端29 kDa纤连蛋白片段（Fn-f）增加软骨的蛋白聚糖（PG）含量而不诱导基质金属蛋白酶（MMP），0.1-1 μ M Fn-f暂时抑制PG合成并增强MMP释放。较高的浓度导致在培养的第一周期间最初快速的PG消耗，随后是慢得多的PG损失和逐渐增加的PG合成速率。为了测试介质的参与，人关节软骨与Fn-f一起培养，并测定条件培养基中选择的细胞因子和因子。使用1 nM Fn-f，在整个28天的培养期间，从培养的软骨中释放的合成代谢因子胰岛素生长因子-I和转化生长因子β 1增加了50- 100%，这与PG合成和PG含量的超常速率有关。然而，较高浓度的Fn-f另外增加了细胞因子的释放，增加了至少10倍，肿瘤坏死因子α、白细胞介素-1 β和白细胞介素-6的释放在最大PG消耗期间或之后的第2、3和9天达到峰值，并分别在第7、7和21天降至对照水平。而白细胞介素6的释放在整个培养期间增强。分解代谢细胞因子的中和抗体减少了Fn-f介导的MMP-3释放和PG合成的抑制。分解代谢和合成代谢因子之间的这种相互作用的时间方面与Fn-f介导的软骨损伤和尝试修复的动力学一致，并且可能与体内软骨损伤和修复相关。
Fibronectin fragments have both catabolic and anabolic activities toward articular cartilage explants in vitro. Whereas a 1 nM concentration of an N-terminal 29 kDa fibronectin fragment (Fn-f) increases the proteoglycan (PG) content of cartilage without induction of matrix metalloproteinases (MMPs), 0.1-1 mu M Fn-f temporarily suppresses PG synthesis and enhances MMP release. The higher concentrations cause an initially rapid PG depletion during the first week of culture, followed by much slower PG loss and gradually increasing rates of PG synthesis. To test for the involvement of mediators, human articular cartilage was cultured with Fn-f, and conditioned media were assayed for selected cytokines and factors. With 1 nM Fn-f, the release of the anabolic factors, insulin growth factor-I and transforming growth factor beta 1, from cultured cartilage was enhanced by 50-100 % during the entire 28-day culture period and this was associated with both supernormal rates of PG synthesis and PG content However, the higher concentrations of Fn-f additionally enhanced release, by at least 10-fold, of the cytokines, tumour necrosis factor alpha, interIeukin-1 alpha, interleukin-1 beta and interleukin-6 while causing depletion of cartilage PG. Release of tumour necrosis factor alpha, interIeukin 1 beta and interleukin la peaked at days 2, 3 and 9 during or slightly after the period of maximal PG depletion and decreased to control levels by days 7, 7 and 21 respectively, whereas release of interleukin 6 was enhanced throughout the culture period. Neutralizing antibodies to the catabolic cytokines reduced Fn-f-mediated MMP-3 release and suppression of PG synthesis. The temporal aspects of this interplay between catabolic and anabolic factors are consistent with the kinetics of Fn-f-mediated cartilage damage and attempted repair and may be relevant to cartilage damage and repair in vivo.