Type IX collagen deficiency enhances the binding of cartilage-specific antibodies and arthritis severity.
Type IX collagen deficiency enhances the binding of cartilage-specific antibodies and arthritis severity.
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DOI：
10.1186/ar1989
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发表时间：
2006
影响因子：
4.9
通讯作者：
Holmdahl R
中科院分区：
文献类型：
--
作者：
Carlsen S;Nandakumar KS;Holmdahl R
关节软骨在自身免疫性炎症和骨关节炎过程中都受到攻击。IX型胶原(CIX)是一种对软骨的完整性和稳定性非常重要的蛋白质。在这项研究中，我们将col9a1基因的转基因中断(导致CIX缺失)回交到两个不同的近交系小鼠DBA/1和B10.Q中。CIX缺陷小鼠都没有出现可观察到的临床或微观骨关节炎，但DBA/1雄性小鼠有更明显的最终病理性关节炎，即所谓的应激性关节炎。DBA/1和B10.Q株都对胶原诱导的关节炎敏感，两株CIX缺乏都会导致比对照组更严重的关节炎。用抗II型胶原(CII)的单抗诱导关节炎，会导致早期的脚掌关节炎，也累及膝关节。所使用的抗体是针对CII的J1和C1I表位的，通过与软骨结合来启动它们的关节炎攻击。C1I特异性抗体在CIX基因缺陷的小鼠中比在野生型动物中更好地与软骨结合，表明软骨中CIX的缺乏导致抗体结合结构的可及性增加，从而使关节更容易受到炎症攻击。这些发现强调了软骨稳定性的重要性；由于遗传疾病造成的软骨破坏可能更容易获得，也更容易受到致病抗体的自身免疫攻击。
Joint cartilage is attacked in both autoimmune inflammatory and osteoarthritic processes. Type IX collagen (CIX) is a protein of importance for cartilage integrity and stability. In this study we have backcrossed a transgenic disruption of the col9a1 gene, which leads to an absence of CIX, into two different inbred mouse strains, DBA/1 and B10.Q. None of the CIX-deficient mice developed observable clinical or microscopic osteoarthritis, but DBA/1 male mice had more pronounced enthesopathic arthritis, the so-called stress-induced arthritis. Both DBA/1 and B10.Q strains are susceptible to the induction of collagen-induced arthritis, and CIX deficiency in both strains led to the development of a more severe arthritis than in the controls. Induction of arthritis with monoclonal antibodies against type II collagen (CII) led to an earlier arthritis in the paws that also involved the knee joints. The antibodies used, which were specific for the J1 and the C1I epitopes of CII, initiate their arthritogenic attack by binding to cartilage. The C1I-specific antibodies bound to cartilage better in CIX-deficient mice than in wild-type animals, demonstrating that the lack of CIX in cartilage leads to an increased accessibility of structures for antibody binding and thus making the joints more vulnerable to inflammatory attack. These findings accentuate the importance of cartilage stability; cartilage disrupted as a result of genetic disorders could be more accessible and vulnerable to an autoimmune attack by pathogenic antibodies.
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影响因子：
14.9
作者：
LAIRD, PW;ZIJDERVELD, A;BERNS, A
通讯作者：
BERNS, A
影响因子：
--
作者：
HOLMDAHL, R;RUBIN, K;WIGZELL, H
通讯作者：
WIGZELL, H
影响因子：
4.1
作者：
Diab, M;Wu, JJ;Eyre, DR
通讯作者：
Eyre, DR
影响因子：
4.4
作者：
Corthay, A;Johansson, Å;Holmdahl, R
通讯作者：
Holmdahl, R
影响因子：
4.6
作者：
HOLMDAHL, R;JANSSON, L;JONSSON, R
通讯作者：
JONSSON, R