Inhibition of osteoclast differentiation and bone resorption by cathepsin K antisense oligonucleotides.

Abstract:

:We confirmed the expression of cathepsin K, the most abundant and specific cysteine protease found in osteoclasts, at the mRNA level in most of our cases of breast cancer, and even at the protein level in bone metastatic lesions. Therefore, we investigated the functions of cathepsin K in osteoclasts with special attention to bone metastasis from breast cancer. Mouse osteoclast-like cells (OCLs) were established by coculture of mouse bone marrow cells and osteoblastic cells. Rodent cathepsin K antisense (AS) or random control (CL) oligonucleotides were added on day 0, 3, or 6 of culture. Tartrate-resistant acid phosphatase staining confirmed the formation of OCLs after 9 d of incubation. AS treatment significantly reduced both the number of TRAP-positive cells and the percentage of multinuclear cells. For the pit-forming assay, after 9 d of incubation, mature OCLs were collected and incubated on ivory slices with AS or CL for 48 h. The antisense oligonucleotides also inhibited the bone-resorbing activity of OCLs. CL treatment did not affect either the number of TRAP-positive cells or pit formation. Cathepsin K may play important roles in bone resorption as well as in differentiation of osteoclasts. These findings indicate that the inhibition of this enzyme may prevent the development of bone metastasis from breast cancer.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Ishikawa T,Kamiyama M,Tani-Ishii N,Suzuki H,Ichikawa Y,Hamaguchi Y,Momiyama N,Shimada H

doi

10.1002/mc.1067

subject

Has Abstract

pub_date

2001-10-01 00:00:00

pages

84-91

issue

2

eissn

0899-1987

issn

1098-2744

pii

10.1002/mc.1067

journal_volume

32

pub_type

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