Osteoprotegerin inhibits tumor-induced osteoclastogenesis and bone tumor growth in osteopetrotic mice

Citation
Dr. Clohisy et al., Osteoprotegerin inhibits tumor-induced osteoclastogenesis and bone tumor growth in osteopetrotic mice, J ORTHOP R, 18(6), 2000, pp. 967-976
Citations number
21
Categorie Soggetti
da verificare
Journal title
JOURNAL OF ORTHOPAEDIC RESEARCH
ISSN journal
07360266 → ACNP
Volume
18
Issue
6
Year of publication
2000
Pages
967 - 976
Database
ISI
SICI code
0736-0266(200011)18:6<967:OITOAB>2.0.ZU;2-E
Abstract
Osteoprotegerin and osteoprotegerin ligand have recently been identified as novel proteins that inhibit and stimulate, respectively, osteoclast format ion. We examined the possibility that osteoprotegerin would inhibit cancer- induced osteoclastogenesis and cancer growth in bone. An experimental model was used in which osteolytic tumors are known to stimulate osteoclastogene sis and grow in femora of osteoclast-deficient mice (op/op). Osteoprotegeri n treatment decreased the number of osteoclasts by 90% (p < 0.0007) at site s of tumor in a dose-dependent manner and decreased bone tumor area by grea ter than 90% (p < 0.003). The mechanisms through which osteoprotegerin decr eased osteoclast formation in tumor-bearing animals included (a) an osteopr otegerin-mediated, systemic reduction in the number of splenic and bone mar row-residing osteoclast precursor cells, (b) a decrease in the number of os teoclast precursor cells at sites of tumor as detected by cathepsin K and r eceptor activator of NF kappaB mRNA expression, and (c) a decrease in osteo protegerin ligand mRNA at sites of tumor. These findings suggest that osteo protegerin treatment, in addition to having direct antagonistic effects on endogenous osteoprotegerin ligand, decreases the number of osteoclast precu rsors and reduces production of osteoprotegerin ligand at sites of osteolyt ic tumor.