論文 - 詳細
| RRC ID | 39639 |
|---|---|
| 著者 | Clohisy DR, Ramnaraine ML, Scully S, Qi M, Van G, Tan HL, Lacey DL. |
| タイトル | Osteoprotegerin inhibits tumor-induced osteoclastogenesis and bone tumor growth in osteopetrotic mice. |
| ジャーナル | J Orthop Res |
| Abstract |
Osteoprotegerin and osteoprotegerin ligand have recently been identified as novel proteins that inhibit and stimulate, respectively, osteoclast formation. 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 osteoclastogenesis and grow in femora of osteoclast-deficient mice (op/op). Osteoprotegerin treatment decreased the number of osteoclasts by 90% (p < 0.0007) at sites of tumor in a dose-dependent manner and decreased bone tumor area by greater than 90% (p < 0.003). The mechanisms through which osteoprotegerin decreased osteoclast formation in tumor-bearing animals included (a) an osteoprotegerin-mediated, systemic reduction in the number of splenic and bone marrow-residing osteoclast precursor cells, (b) a decrease in the number of osteoclast precursor cells at sites of tumor as detected by cathepsin K and receptor activator of NFkappaB mRNA expression, and (c) a decrease in osteoprotegerin ligand mRNA at sites of tumor. These findings suggest that osteoprotegerin treatment, in addition to having direct antagonistic effects on endogenous osteoprotegerin ligand, decreases the number of osteoclast precursors and reduces production of osteoprotegerin ligand at sites of osteolytic tumor. |
| 巻・号 | 18(6) |
| ページ | 967-76 |
| 公開日 | 2000-11-1 |
| DOI | 10.1002/jor.1100180617 |
| PMID | 11192258 |
| MeSH | Animals Bone Neoplasms / complications Bone Neoplasms / drug therapy* Bone Neoplasms / physiopathology Carrier Proteins / genetics Disease Models, Animal Dose-Response Relationship, Drug Femur / drug effects Femur / pathology Femur / surgery Gene Expression Regulation, Neoplastic / drug effects Gene Expression Regulation, Neoplastic / physiology Glycoproteins / pharmacology* Macrophage Colony-Stimulating Factor / genetics Membrane Glycoproteins / genetics Mice Mice, Inbred Strains Osteoclasts / cytology Osteoclasts / drug effects* Osteoclasts / metabolism Osteolysis / drug therapy* Osteolysis / etiology Osteolysis / physiopathology Osteopetrosis / pathology Osteopetrosis / physiopathology Osteoprotegerin Parathyroid Hormone-Related Protein Proteins / genetics RANK Ligand RNA, Messenger / drug effects RNA, Messenger / metabolism Receptor Activator of Nuclear Factor-kappa B Receptors, Cytoplasmic and Nuclear Receptors, Tumor Necrosis Factor Stem Cells / cytology Stem Cells / drug effects Stem Cells / metabolism Stromal Cells / cytology Stromal Cells / drug effects Stromal Cells / metabolism Tumor Cells, Cultured / drug effects Tumor Cells, Cultured / pathology Tumor Cells, Cultured / transplantation |
| IF | 2.728 |
| 引用数 | 36 |
| WOS 分野 | ORTHOPEDICS |
| リソース情報 | |
| ヒト・動物細胞 | |