Calvarial osteoclasts express a higher level of tartrate-resistant acid phosphatase than long bone osteoclasts and activation does not depend on cathepsin K or L activity
Calvarial osteoclasts express a higher level of tartrate-resistant acid phosphatase than long bone osteoclasts and activation does not depend on cathepsin K or L activity
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DOI：
10.1007/s00223-005-0289-z
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发表时间：
2006-10-01
影响因子：
4.2
通讯作者：
Everts, V.
中科院分区：
文献类型：
--
作者：
Perez-Amodio, S.;Jansen, D. C.;Everts, V.
破骨细胞的骨吸收取决于各种蛋白水解酶的活性，特别是那些属于半胱氨酸蛋白酶组的酶。在这些酶旁边，抗酒石酸酸性磷酸酶（TRAP）被认为参与了这一过程。TRAP是作为一种无活性的前酶合成的，体外研究表明它可以被半胱氨酸蛋白酶激活。在本研究中，研究人员利用组织蛋白酶K和/或L缺乏的小鼠以及表达高（长骨）或低（颅骨）半胱氨酸蛋白酶活性的骨骼，研究了后一类酶可能参与TRAP的体内调节。结果表明，在缺乏组织蛋白酶K的小鼠中，而在缺乏组织蛋白酶L的小鼠中，长骨中的TRAP活性水平显著升高。这种较高的活性是由于破骨细胞的数量较多。接下来，我们发现颅骨和长骨之间TRAP活性存在相当大的差异。颅骨的活动水平是长骨的25倍。无论基因型如何，这种差异在所有小鼠中都可以看到。从两种类型的骨中分离的破骨细胞显示，颅骨破骨细胞表达更高的酶活性以及更高水平的酶mRNA。对trap缺陷小鼠的分析显示，与长骨破骨细胞相比，颅骨破骨细胞内和周围的未消化骨基质成分水平更高。最后，特定抑制剂抑制半胱氨酸蛋白酶活性导致TRAP活性增加。我们的数据表明组织蛋白酶K和L都不是激活TRAP所必需的。研究结果还指出，在TRAP参与骨基质降解方面，来自不同骨部位的破骨细胞的功能差异。我们认为，与长骨细胞相比，颅骨破骨细胞中较高水平的TRAP活性可能部分补偿了颅骨破骨细胞中较低的半胱氨酸蛋白酶活性，并且TRAP可能有助于在这种类型的骨消化过程中非胶原蛋白的降解。
Bone resorption by osteoclasts depends on the activity of various proteolytic enzymes, in particular those belonging to the group of cysteine proteinases. Next to these enzymes, tartrate-resistant acid phosphatase (TRAP) is considered to participate in this process. TRAP is synthesized as an inactive proenzyme, and in vitro studies have shown its activation by cysteine proteinases. In the present study, the possible involvement of the latter enzyme class in the in vivo modulation of TRAP was investigated using mice deficient for cathepsin K and/or L and in bones that express a high (long bone) or low (calvaria) level of cysteine proteinase activity. The results demonstrated, in mice lacking cathepsin K but not in those deficient for cathepsin L, significantly higher levels of TRAP activity in long bone. This higher activity was due to a higher number of osteoclasts. Next, we found considerable differences in TRAP activity between calvarial and long bones. Calvarial bones contained a 25-fold higher level of activity than long bones. This difference was seen in all mice, irrespective of genotype. Osteoclasts isolated from the two types of bone revealed that calvarial osteoclasts expressed higher enzyme activity as well as a higher level of mRNA for the enzyme. Analysis of TRAP-deficient mice revealed higher levels of nondigested bone matrix components in and around calvarial osteoclasts than in long bone osteoclasts. Finally, inhibition of cysteine proteinase activity by specific inhibitors resulted in increased TRAP activity. Our data suggest that neither cathepsin K nor L is essential in activating TRAP. The findings also point to functional differences between osteoclasts from different bone sites in terms of participation of TRAP in degradation of bone matrix. We propose that the higher level of TRAP activity in calvarial osteoclasts compared to that in long bone cells may partially compensate for the lower cysteine proteinase activity found in calvarial osteoclasts and TRAP may contribute to the degradation of noncollagenous proteins during the digestion of this type of bone.