Guo D, Ding L, Homandberg G A
Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, 58202, USA.
Inflamm Res. 2009 Mar;58(3):161-9. doi: 10.1007/s00011-009-8090-5.
We hypothesize that N-telopeptide (NT) and C-telopeptides (CT) of type II collagen can enhance proteinases and cause cartilage damage and have compared damaging activities to an extensively characterized potent fibronectin fragment (Fn-f).
NT and CT peptides were synthesized.
Interaction of labeled peptides with chondrocytes was studied by fluorescence microscopy. Effects on the metalloproteinases (MMPs) MMP-3 and MMP-13 and on ADAMTS-5 were analyzed by western blotting. Cartilage damage was assayed by loss of proteoglycan (PG) from cultured explants.
NT and CT peptides penetrated cartilage, bound to chondrocytes and enhanced proteinase release and cartilage PG depletion. Peptides had detectable activity at 0.3 microM (1 microg/ml) and were comparable at 30 microM (100 microg/ml) to 1 microM Fn-f (29 microg/ml). However, while the Fn-f enhanced IL-1beta and TNF-alpha, the NT and CT peptides did not.
Collagen peptides containing NT and CT regions were less active on a molar basis than Fn-fs but were still potent damaging agents. Since collagen fragments are found in OA cartilage at microg/ml, they have the potential to play a role in physiologic cartilage damage.
我们推测II型胶原蛋白的N - 末端肽（NT）和C - 末端肽（CT）可增强蛋白酶活性并导致软骨损伤，并将其损伤活性与一种已被广泛表征的强效纤连蛋白片段（Fn - f）进行了比较。
合成了NT和CT肽。
通过荧光显微镜研究标记肽与软骨细胞的相互作用。采用蛋白质印迹法分析对金属蛋白酶（MMPs）MMP - 3和MMP - 13以及对ADAMTS - 5的影响。通过测定培养外植体中蛋白聚糖（PG）的损失来检测软骨损伤情况。
NT和CT肽可穿透软骨，与软骨细胞结合，并增强蛋白酶释放和软骨PG消耗。肽在0.3微摩尔（1微克/毫升）时具有可检测到的活性，在30微摩尔（100微克/毫升）时与1微摩尔Fn - f（29微克/毫升）相当。然而，虽然Fn - f可增强IL - 1β和TNF - α，但NT和CT肽则不然。
含有NT和CT区域的胶原蛋白肽在摩尔基础上的活性低于Fn - f，但仍是强效损伤剂。由于在骨关节炎软骨中发现胶原蛋白片段的浓度为微克/毫升级别，它们有可能在生理性软骨损伤中发挥作用。
