Matrix homeostasis in aging normal human ankle cartilage
Matrix homeostasis in aging normal human ankle cartilage
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DOI：
10.1002/art.10611
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发表时间：
2002-11-01
影响因子：
--
通讯作者：
Cole, AA
中科院分区：
文献类型：
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作者：
Aurich, M;Poole, AR;Cole, AA
目标。研究与年龄相关(而不是关节炎相关)的胶原蛋白和蛋白多糖转换的变化。取30例年龄16~75岁的大体非退行性正常踝关节软骨进行原位杂交检测IIB型胶原(CIIB)的信使RNA(信使RNA)，并用11型胶原C-前肽(CPII)、II型胶原(CII)胶原酶裂解新表位(简称CO12-3/4C)和CII变性产物(CO12-3/4M)的抗体进行免疫组织化学分析和免疫分析。免疫印迹法检测4种胶原酶。检测糖胺多聚糖(GAG)含量和Aggrecan的846表位。CII、GAG和846表位的含量在30年后无明显变化。CIIB和CPII的信使核糖核酸在各带均有表达，CPII含量随年龄变化不明显。胶原酶裂解的CII有随年龄增长而增加的趋势，而变性的胶原则不随年龄增加而增加。但裂解胶原与变性胶原的摩尔比与年龄呈正相关。4种胶原酶在踝关节软骨中均可检测到，但随着年龄的增长，胶原酶的含量没有明显变化。CII的合成和降解与细胞周围基质有关，并在整个生命过程中保持稳定状态。CII和蛋白多糖含量无明显变化。与胶原酶介导的切割相比，随着年龄的增长，CII的变性程度显著降低。这些观察表明，在完整的踝关节软骨老化过程中，没有证据表明存在骨关节炎中观察到的那种分子退行性变化，从而将衰老与骨关节炎过程区分开来。
Objective. To study age-related (as opposed to arthritis-related) changes in collagen and proteoglycan turnover.Methods. Macroscopically nondegenerate normal ankle cartilage obtained from 30 donors (ages 16-75 years) was processed for in situ hybridization to detect messenger RNA (mRNA) of type IIB collagen (CIIB); antibodies to the C-propeptide of type 11 collagen (CPII), to the type II collagen (CII) collagenase-generated cleavage neoepitope (Co12-3/4C(short)), and to the CII denaturation product (Co12-3/4m) were used for immunohistochemistry analysis and immunoassay. In addition, immunoblotting was used to detect the 4 collagenases. Assays were also performed to detect glycosaminoglycan (GAG) content and the 846 epitope of aggrecan.Results. There were no significant changes in CII, GAG, and the content of the 846 epitope after the age of 30 years. Both mRNA for CIIB and the CPII were present in all-zones, and CPII content did not change significantly with age. While the collagenase-cleaved CII showed a trend to increase with age, the denatured collagen did not. However, the molar ratio of cleaved versus denatured collagen was positively correlated with age. All 4 collagenases were detectable in the ankle cartilage but showed no identifiable changes in content with age.Conclusion. Synthesis and degradation of CII is associated with the pericellular matrix and is maintained at a steady state throughout life. The contents of CII and proteoglycan did not change. There was a significant reduction in the denaturation of CII with age, relative to collagenase-mediated cleavage. These observations reveal that, in aging of the intact ankle articular cartilage, there is no evidence of molecular degenerative changes of the kind observed in osteoarthritis, thereby distinguishing aging from the osteoarthritis process.