Littlewood-Evans A, Kokubo T, Ishibashi O, Inaoka T, Wlodarski B, Gallagher J A, Bilbe G
Pharma Research, Ciba-Geigy Ltd., Basel, Switzerland.
Bone. 1997 Feb;20(2):81-6. doi: 10.1016/s8756-3282(96)00351-1.
We have recently cloned cathepsin K from a human bone cDNA library. Since cathepsins are proposed to be involved in the degradation of mineralized bone matrix, we have investigated, by in situ hybridization and immunocytochemistry, the expression of the cathepsin K mRNA transcripts and protein in sections of bone and giant cell tumor to determine which cells express this enzyme. Within all tissues studied, cathepsin K was highly expressed in osteoclasts. Furthermore, the expression of cathepsin K mRNA in giant cell tumor tissue appeared to be confined to the periphery of the osteoclast indicating a compartmentalization of the mRNA. Immunohistochemistry confirmed the specific localization of cathepsin K to the osteoclast. In actively resorbing osteoclasts, the immunostaining was localized at the ruffled border, whereas in osteoclasts in sections of giant cell tumor, staining was observed in lysosomal vacuoles, which in some cases were seen to fuse with the cell membrane. Other cells within the bone, such as osteoblasts and osteocytes, did not express either the cathepsin K transcript or protein. However, there were very low levels of cathepsin K detected in a population of mononuclear cells, possibly representing osteoclast progenitor cells, within the marrow/stromal layer. The specific localization of cathepsin K within osteoclasts would therefore indicate the potential role of this enzyme in the bone resorptive process.
我们最近从人骨cDNA文库中克隆了组织蛋白酶K。由于组织蛋白酶被认为参与矿化骨基质的降解，我们通过原位杂交和免疫细胞化学方法，研究了组织蛋白酶K mRNA转录本和蛋白在骨组织切片及骨巨细胞瘤中的表达情况，以确定哪些细胞表达这种酶。在所有研究的组织中，组织蛋白酶K在破骨细胞中高表达。此外，在骨巨细胞瘤组织中，组织蛋白酶K mRNA的表达似乎局限于破骨细胞的周边，这表明mRNA存在区域化分布。免疫组织化学证实了组织蛋白酶K在破骨细胞中的特异性定位。在活跃进行骨吸收的破骨细胞中，免疫染色定位于皱褶缘，而在骨巨细胞瘤切片中的破骨细胞中，染色则见于溶酶体空泡，在某些情况下可见这些空泡与细胞膜融合。骨内的其他细胞，如成骨细胞和骨细胞，既不表达组织蛋白酶K转录本也不表达其蛋白。然而，在骨髓/基质层内的一群单核细胞中检测到了非常低水平的组织蛋白酶K，这些单核细胞可能代表破骨细胞前体细胞。因此，组织蛋白酶K在破骨细胞内的特异性定位表明该酶在骨吸收过程中可能发挥作用。
