Acid attack and cathepsin K in bone resorption around total hip replacement prosthesis
Acid attack and cathepsin K in bone resorption around total hip replacement prosthesis
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DOI：
10.1359/jbmr.2001.16.10.1780
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发表时间：
2001-10-01
影响因子：
6.2
通讯作者：
Santavirta, S
中科院分区：
文献类型：
--
作者：
Konttinen, YT;Takagi, M;Santavirta, S
正常的骨重建和病理性的骨破坏被认为是破骨细胞驱动的。破骨细胞能够附着在裸露的骨表面，并产生酸性的亚细胞空间。这会导致羟基磷灰石的酸性溶解，使组织蛋白酶K在Howship Lacunae普遍存在的酸性条件下降解富含I型胶原的有机类骨基质。使用刺状pH电极，发现松动的全髋关节假体周围的界面膜是酸性的。激光共聚焦扫描发现与酸性界面接触的骨表面有不规则的脱矿现象。组织蛋白酶K是一种酸性胶原酶，存在于巨噬细胞/巨细胞界面组织和假性滑膜积液中。组织提取液中含有较高水平的组织蛋白酶K信使RNA和蛋白质。这些观察结果表明，存在一种由酸和组织蛋白酶K驱动的骨吸收病理机制，这种机制不是由破骨细胞介导的，而是由细胞外空间巨噬细胞的不受控制的活动介导的。
Normal bone remodeling and pathological bone destruction have been considered to be osteoclast-driven. Osteoclasts are able to attach to bare bone surface and produce an acidic subcellular space. This leads to acid dissolution of hydroxyapatite, allowing cathepsin K to degrade the organic type I collagen-rich osteoid matrix under the acidic condition prevailing in Howship lacunae. Using a sting pH electrode, the interface membrane around a loosened total hip replacement prosthesis was found to be acidic. Confocal laser scanning disclosed irregular demineralization of the bone surface in contact with the acidic interface. Cathepsin K, an acidic collagenolytic enzyme, was found in interface tissue macrophages/giant cells and pseudosynovial fluid. Tissue extracts contained high levels of cathepsin K messenger RNA (mRNA) and protein. These observations suggest the presence of an acid- and cathepsin K-driven pathological mechanism of bone resorption, mediated not by osteoclasts in subosteoclastic space, but rather by the uncontrolled activity of macrophages in extracellular space.