Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts

被引:606
作者
Drake, FH
Dodds, RA
James, IE
Connor, JR
Debouck, C
Richardson, S
LeeRykaczewski, E
Coleman, L
Rieman, D
Barthlow, R
Hastings, G
Gowen, M
机构
[1] SMITHKLINE BEECHAM PHARMACEUT,DEPT MOLEC GENET,KING OF PRUSSIA,PA 19406
[2] HUMAN GENOME SCI INC,ROCKVILLE,MD 20850
关键词
D O I
10.1074/jbc.271.21.12511
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Random high throughput sequencing of a human osteoclast cDNA library was employed to identify novel osteoclast-expressed genes. Of the 5475 ESTs obtained, approximately 4% encoded cathepsin K, a novel cysteine protease homologous to cathepsins S and L; ESTs for other cathepsins were rare. In addition, ESTs for cathepsin K were absent or at low frequency in cDNA libraries from numerous other tissues and cells. In situ hybridization in osteoclastoma and osteophyte confirmed that cathepsin K mRNA was highly expressed selectively in osteoclasts; cathepsins S, L, and B were not detectable. Cathepsin K was not detected by in situ hybridization in a panel of other tissues. Western blot of human osteoclastoma or fetal rat humerus demonstrated bands of 38 and 27 kDa, consistent with sizes predicted for pro- and mature cathepsin K. Immunolocalization in osteoclastoma and osteophyte showed intense punctate staining of cathepsin K exclusively in osteoclasts, with a polar distribution that was more intense at the bone surface. The abundant expression of cathepsin K selectively in osteoclasts strongly suggests that it plays a specialized role in bone resorption. Furthermore, the data suggest that random sequencing of ESTs from cDNA libraries is a valuable approach for identifying novel cell-selective genes.
引用
收藏
页码:12511 / 12516
页数:6
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