Luo Yunyun, He Yi, Karsdal Morten, Bay-Jensen Anne-Christine
Dept. of ImmunoScience, Biomarkers & Research, Nordic Bioscience A/S, Herlev, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Osteoarthr Cartil Open. 2020 Jun 8;2(3):100082. doi: 10.1016/j.ocarto.2020.100082. eCollection 2020 Sep.
Type II collagen is the most abundant protein of articular cartilage. The urinary cross-linked C-terminal telopeptide of type II collagen (uCTX-II) is a matrix metalloproteinase (MMP) cleaved fragment and may be the most well-validated biomarker in osteoarthritis. The aim was to develop a serological immunoassay of CTX-II (sCTX-II) and evaluated both sCTX-II and uCTX-II levels in a cross-sectional osteoarthritis cohort.
The biological relevance of sCTX-II was validated in bovine cartilage explants cultured in the presence of Oncostatin M and tumor necrosis factor alpha (OT) or OT supplemented with GM6001 for 3 weeks. Serum and urine samples from an osteoarthritis cohort were assayed using sCTX-II and uCTX-II, respectively. Spearman's correlation was performed to evaluate the correlation between sCTX-II and uCTX-II. The association between the level of biomarkers and clinical variables was also investigated.
The supernatant analyzed in sCTX-II showed significant higher CTX-II levels in the end phases of explant culture compared to the vehicle group. The release of CTX-II was completely suppressed by GM6001. The sCTX-II levels in serum were not associated with uCTX-II in urine although sCTX-II levels in urine were significantly correlated with uCTX-II. uCTX-II correlated with age and gender while sCTX-II did not. sCTX-II cannot demonstrate any clinical relevance in a cross-sectional OA cohort as uCTX-II did.
The sCTX-II assay can reflect the MMP-mediated type II collagen degradation in bovine cartilage explants. However, sCTX-II and uCTX-II assays show different patterns suggesting the presence of CTX-II in blood may be different from that of urine.
II型胶原蛋白是关节软骨中含量最丰富的蛋白质。II型胶原蛋白的尿交联C末端肽段（uCTX-II）是一种基质金属蛋白酶（MMP）裂解片段，可能是骨关节炎中最经充分验证的生物标志物。本研究旨在开发一种CTX-II的血清免疫测定法（sCTX-II），并在一个横断面骨关节炎队列中评估sCTX-II和uCTX-II水平。
在存在制瘤素M和肿瘤坏死因子α（OT）或添加GM6001的OT的情况下培养3周的牛软骨外植体中验证sCTX-II的生物学相关性。分别使用sCTX-II和uCTX-II检测骨关节炎队列的血清和尿液样本。采用Spearman相关性分析评估sCTX-II与uCTX-II之间的相关性。还研究了生物标志物水平与临床变量之间的关联。
与空白组相比，sCTX-II分析的上清液在培养末期显示出显著更高的CTX-II水平。GM6001完全抑制了CTX-II的释放。血清中的sCTX-II水平与尿液中的uCTX-II无关，尽管尿液中的sCTX-II水平与uCTX-II显著相关。uCTX-II与年龄和性别相关，而sCTX-II则不然。与uCTX-II不同，sCTX-II在横断面OA队列中未显示出任何临床相关性。
sCTX-II检测可反映牛软骨外植体中MMP介导的II型胶原蛋白降解。然而，sCTX-II和uCTX-II检测显示出不同的模式，提示血液中CTX-II的存在可能与尿液中的不同。
