A type I collagen defect leads to rapidly progressive osteoarthritis in a mouse model
A type I collagen defect leads to rapidly progressive osteoarthritis in a mouse model
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DOI：
10.1002/art.23277
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发表时间：
2008-04-01
影响因子：
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通讯作者：
Lipsky, P. E.
中科院分区：
文献类型：
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作者：
Blair-Levy, J. M.;Watts, C. E.;Lipsky, P. E.
Objective.本研究旨在验证软骨下骨异常可导致骨关节炎（OA）的假设。我们使用了一个敲入模型的人成骨细胞，脆性IV（Brtl）小鼠，其中有缺陷的I型胶原蛋白在骨中表达。通过显微磁共振成像（micro-MRI）和显微计算机断层扫描（micro-CT）记录了个体小鼠的OA。通过组织病理学和免疫组织化学分析证实膝关节的改变。应用原子力显微镜（AFM）观察关节软骨和软骨下骨基质的超微结构。Brtl小鼠骨完整性降低，但最初关节软骨正常。然而，到出生后第二个月，Brt 1小鼠出现了OA特征性的软骨改变，如通过显微CT、显微MRI和组织学评价所记录的。此外，使用AFM证实了残余软骨中的软骨细胞损失和胶原基质的破坏。Brtl小鼠模型表明，OA特征性关节软骨的进行性破坏可能继发于底层软骨下骨的结构改变。
Objective. This study was undertaken to test the hypothesis that abnormalities of the subchondral bone can result in osteoarthritis (OA).Methods. We used a knockin model of human osteogenesis imperfecta, the Brittle IV (Brtl) mouse, in which defective type I collagen is expressed in bone. OA in individual mice was documented by micro-magnetic resonance imaging (micro-MRI) and micro-computed tomography (micro-CT). Alterations in the knee joints were confirmed by histopathologic and immunohistochemical analysis. In addition, atomic force microscopy (AFM) was used to assess the ultrastructure of the articular cartilage and subchondral bone matrix.Results. Brtl mice had decreased integrity of bone but initially normal articular cartilage. However, by the second month of life, Brtl mice developed alterations of the cartilage that were characteristic of OA, as documented by micro-CT, micro-MRI, and histologic evaluation. In addition, chondrocyte loss and breakdown of the collagen matrix in the residual cartilage were demonstrated using AFM.Conclusion. The Brtl mouse model demonstrates that progressive destruction of articular cartilage characteristic of OA may be secondary to altered architecture of the underlying subchondral bone.