Fibromodulin-null murine knee joints display increased incidences of osteoarthritis and alterations in tissue biochemistry
Fibromodulin-null murine knee joints display increased incidences of osteoarthritis and alterations in tissue biochemistry
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DOI：
10.1053/joca.2002.0527
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发表时间：
2002-10-01
影响因子：
7
通讯作者：
Reinholt, FP
中科院分区：
文献类型：
--
作者：
Gill, MR;Oldberg, Å;Reinholt, FP
目的：探讨纤维调素(FM)基因缺失小鼠和野生型(WT)小鼠的组织超微结构和病理发生率的差异。设计：比较不同年龄段FM基因缺失和野生型(WT)小鼠的组织超微结构和病理发生率。石蜡包埋全膝连续切片，进行组织学观察。结果：组织学结果显示，随着年龄的增长，WT和FM缺失型动物膝关节的组织退行性变之间的差异越来越明显。在36周时，明显的差异是明显的。大约在80周前后，这些差异变得深刻起来。然而，定性的超微结构检查没有发现任何异常的组织超微结构或在FM缺失的关节软骨中有任何异常的胶原纤维形成。Fm缺失关节软骨的生化和免疫组织化学研究显示，Lum的组织水平显著增加。相反，膝关节十字韧带显示出Lum含量的增加和相当大的结构异常，包括断裂的倾向。结论：本报告首次表明FM基因缺失的小鼠比可比的WT动物具有更高的膝关节退行性变化的倾向。有趣的是，关节软骨中没有潜在的超微结构或纤维异常可以解释为什么FM缺失的软骨比野生型组织更容易发生病理变化。我们得出结论，韧带的改变，可能还有膝关节内其他组织的改变，在观察到的关节软骨退变的发病机制中具有相当重要的作用。(C)2002年国际骨性关节炎研究会。爱思唯尔科学有限公司出版。版权所有。
Objective: To elucidate variations in tissue ultrastructure and incidence of pathology between fibromodulin (FM)-null mice and wild-type (WT) animals.Design: FM-null and WT siblings from different age groups were compared. Serial sections were made through paraffin-embedded whole knees and investigated histologically. Additionally, medial femoral condyle peaks from sibling pairs were investigated ultrastructurally using transmission electron microscopy.Results: Histological findings demonstrated a clear and increasing disparity between tissue degeneration in WT and FM-null animal knees with progressing age. Distinct differences were apparent by 36 weeks. Around the 80 week period and onward these differences became profound. However, qualitative ultrastructural investigation did not indicate either any aberrant tissue ultrastructure or any abnormal collagen fibril forms in FM-null articular cartilage compared with WT. Biochemical and immunohistochemical investigation of FM-null articular cartilage showed a significant increase in tissue levels of lumican (LUM). Conversely, the cruciate ligaments of the knee showed both an increase in LUM content and considerable structural abnormalities including the tendency towards rupture.Conclusion: This report indicates for the first time that FM-null mice have a higher propensity towards degenerative changes in their knee joints than comparable WT animals. Interestingly, no underlying ultrastructural or fibril abnormalities within the articular cartilage could be identified to explain why FM-null cartilage is more prone to pathological changes than wild-type tissue. We conclude that alterations in ligaments, and possibly other tissues within the knee, are of considerable importance in the pathogenesis of the observed articular cartilage degeneration. (C) 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.