De Ceuninck Frederic, Sabatini Massimo, Renoux Veronique, de Nanteuil Guillaume, Pastoureau Philippe
Department of Rheumatology, Institut de Recherches Servier, Suresnes, France.
J Rheumatol. 2003 Jul;30(7):1561-4.
To assess the relevance of collagen type II C-telopeptide fragments (CTX-II) as markers of cartilage degradation during adjuvant-induced arthritis in rats.
Rats were injected with Freund's adjuvant on day 0 and treated orally for 21 days twice a day with vehicle or 10 or 20 mg/kg of a newly designed matrix metalloproteinase inhibitor (MMP-Inh). Urine samples were collected for 24 h between days 19 and 20 and the concentration of the cartilage-derived CTX-II was measured with a 2-site, sandwich-type ELISA. To assess arthritis, inflammatory scores were determined, and changes in paw volumes were measured by plethysmography.
On day 21, the inflammation was generalized in rats injected with Freund's adjuvant. The urinary concentration of CTX-II was significantly higher in arthritic rats than in control non-injected rats. Oral treatment of arthritic rats with MMP-Inh dramatically decreased the concentration of CTX-II in urine, with values returning to those of controls. Treatment simultaneously reduced the clinical variables of the disease.
These results demonstrate that fragments of type II collagen in urine can be used as a measure of cartilage degradation in arthritic rats as well as potent non-invasive markers of the efficacy of chondroprotective treatments.
评估II型胶原C末端肽片段（CTX-II）作为佐剂诱导的大鼠关节炎中软骨降解标志物的相关性。
在第0天给大鼠注射弗氏佐剂，并于第19天至第20天期间每天两次口服给予赋形剂或10或20mg/kg新设计的基质金属蛋白酶抑制剂（MMP-Inh），持续21天。收集第19天至第20天期间24小时的尿液样本，并用双位点夹心型酶联免疫吸附测定法（ELISA）测量软骨来源的CTX-II浓度。为评估关节炎，测定炎症评分，并用体积描记法测量爪体积的变化。
在第21天，注射弗氏佐剂的大鼠出现全身性炎症。关节炎大鼠尿液中CTX-II的浓度显著高于未注射的对照大鼠。用MMP-Inh对关节炎大鼠进行口服治疗可显著降低尿液中CTX-II的浓度，使其值恢复到对照水平。治疗同时降低了疾病的临床变量。
这些结果表明，尿液中的II型胶原片段可作为关节炎大鼠软骨降解的指标，以及软骨保护治疗效果的有效非侵入性标志物。
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