Abstracts of poster presentations

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 190 KB
• Volume: 88
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/1097-0142(20000615)88:12+<3089::aid-cncr28>3.0.co;2-2

✦ Synopsis

Osteoprotegerin (OPG) and OPG ligand (L) have recently been identified as novel proteins that inhibit and stimulate, respectively, osteoclast formation. In this investigation, the authors examined the possibility that OPG would inhibit cancerinduced osteoclastogenesis and cancer growth in bone. An experimental model was used in which osteolytic tumors were known to stimulate osteoclastogenesis and grow in the femora of osteoclast-deficient mice (op/op) (J Ortho Res 1995;13: 892). Mice were treated with either OPG (0.1-5 mg/kg/day) or saline and sacrificed 14 days after intrafemoral injection of the osteolytic tumor cell line. Femora, bone marrow, and spleen cells were then evaluated. OPG treatment decreased the osteoclast number by 90% (P Ͻ 0.05) at sites of tumor in a dose-dependent manner and decreased bone tumor area by greater than 90% (P Ͻ 0.003) The mechanisms through which OPG decreased osteoclast formation in tumor-bearing animals included 1) an OPG-mediated, systemic reduction (70% decrease, P Ͻ 0.002) in the number of splenic and bone marrow-residing osteoclast precursor cells, 2) a decrease in the number of osteoclast precursor cells at sites of tumor as detected by cathepsin K expression and in situ hybridization (ISH) for receptor activator of NF-kB (RANK) mRNA, and 3) a decrease in OPGL at sites of tumor as determined by ISH for OPGL mRNA. These findings suggest that OPG treatment, in addition to having direct antagonistic effects on endogenous OPGL, decreases the number of osteoclast precursors and reduces production of OPGL at sites of osteolytic tumor.