Lady Davis Institute for Medical Research, SMBD-Jewish General Hospital, Montreal, QC, Canada.
Tissue Eng Part A. 2011 Apr;17(7-8):899-904. doi: 10.1089/ten.TEA.2010.0494. Epub 2010 Dec 31.
Intervertebral disc (IVD) degeneration is associated with proteolytic degradation of proteoglycan aggregates present within the extracellular matrix of the disc. Link N peptide (DHLSDNYTLDHDRAIH) is the N-terminal peptide of link protein, which stabilizes the proteoglycan aggregates. It is generated in vivo by proteolytic degradation during tissue turnover. It has been previously shown that this peptide can stimulate the synthesis of collagens by articular cartilage and bovine IVD cells in vitro. Being a synthetic peptide, Link N has considerable financial benefits for clinical use over recombinant growth factors because it is extremely cheap to produce. The purpose of the present study was to determine the effect of Link N on the expression of types I and II collagen and investigate the cellular mechanisms of Link N signal transduction in human IVD cells. The present results suggest that Link N stimulates the expression of types I and II collagen in human IVD cells. More specifically, Link N stimulated the expression of type I in nucleus pulposus (NP) cells, but not in annulus fibrosus cells. As Link N also decreased the phosphorylation of p38 in NP cells only, results suggest that p38 is a mediator of the effect of Link N on type I collagen expression. p38 is a member of the mitogen-activated protein kinase family highlighted by three major cascades: p38, c-Jun amino-terminal kinase, and extracellular signal-regulated kinase pathways. Link N showed no effect on the latter two pathways, suggesting a specific effect of Link N on the p38 cascade. On the other hand, Link N stimulated the expression of type II collagen in both NP and annulus fibrosus, suggesting that other mechanisms are implicated in the control of type II collagen expression in disc cells, without excluding p38 for the NP. In conclusion, the present study showed that Link N can modulate the expression of collagen in human IVD cells.
椎间盘（IVD）退变与存在于椎间盘细胞外基质中的蛋白聚糖聚集体的蛋白水解降解有关。连接 N 肽（DHLSDNYTLDHDRAIH）是连接蛋白的 N 端肽，可稳定蛋白聚糖聚集体。它是在组织更新过程中通过蛋白水解降解在体内产生的。先前已经表明，该肽可以刺激关节软骨和牛 IVD 细胞体外合成胶原蛋白。作为一种合成肽，与重组生长因子相比，Link N 具有相当大的临床应用经济优势，因为它的生产成本非常低廉。本研究的目的是确定 Link N 对 I 型和 II 型胶原蛋白表达的影响，并研究 Link N 在人 IVD 细胞中的信号转导的细胞机制。本研究结果表明 Link N 可刺激人 IVD 细胞中 I 型和 II 型胶原蛋白的表达。更具体地说，Link N 刺激 NP 细胞中 I 型胶原蛋白的表达，但不刺激纤维环细胞中 I 型胶原蛋白的表达。由于 Link N 还仅降低 NP 细胞中 p38 的磷酸化，结果表明 p38 是 Link N 对 I 型胶原蛋白表达影响的介质。p38 是丝裂原激活蛋白激酶家族的成员，该家族突出了三个主要的级联：p38、c-Jun 氨基末端激酶和细胞外信号调节激酶途径。Link N 对后两个途径没有影响，表明 Link N 对 p38 级联有特异性作用。另一方面，Link N 刺激 NP 和纤维环中 II 型胶原蛋白的表达，这表明在椎间盘细胞中控制 II 型胶原蛋白表达涉及其他机制，而不排除 p38 对 NP 的影响。总之，本研究表明 Link N 可以调节人 IVD 细胞中胶原蛋白的表达。
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