A Third-Generation Bisphosphonate, YM175, Inhibits Osteoclast Formation in Murine Cocultures by Inhibiting Proliferation of Precursor Cells via Supporting Cell-Dependent Mechanisms
| Autor: | Miyuki Nishikawa, Michiko Yamamoto, Takehiko Murakami, Naokazu Nagata, Takuhiko Akatsu, Nobuo Kugai |
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| Rok vydání: | 1998 |
| Předmět: |
musculoskeletal diseases
Stromal cell Endocrinology Diabetes and Metabolism medicine.medical_treatment Anti-Inflammatory Agents Osteoclasts Bone Marrow Cells Spleen Methylcellulose Biology Giant Cells Dexamethasone Cell Fusion Mice Multinucleate Osteoclast Precursor cell medicine Animals Orthopedics and Sports Medicine Osteoblasts Diphosphonates Dose-Response Relationship Drug Bisphosphonate Coculture Techniques Third generation Culture Media Cell biology medicine.anatomical_structure Biochemistry Bone marrow Stromal Cells Cell Division |
| Zdroj: | Journal of Bone and Mineral Research. 13:986-995 |
| ISSN: | 0884-0431 |
| DOI: | 10.1359/jbmr.1998.13.6.986 |
| Popis: | The theory that bisphosphonates inhibit osteoclast formation through their effects on osteoblastic cells remains controversial. To confirm the inhibitory effect of bisphosphonates on osteoclast formation and gain some insights into the underlying mechanisms, we examined the effect of disodium dihydrogen (cycloheptylamino)-methylene-bisphosphonate monohydrate (YM175) on osteoclast-like multinucleated cell (OCL) formation in various mouse coculture systems. When different origins of osteoclast precursors (bone marrow, spleen, or nonspecific esterase-positive cells) were cocultured with the same supporting cells (calvarial osteoblasts), YM175 inhibited OCL formation similarly in all cultures. When the same osteoclast precursors (spleen cells) were cocultured with supporting cells of different origin, the results were variable. YM175 inhibited OCL formation almost completely in cocultures with calvarial osteoblasts or osteoblastic cell line KS4, while it did not, or only slightly, inhibit OCL formation in cocultures with stromal cell lines, ST2 or MC3T3-G2/PA6. Temporal addition of YM175 in cocultures of spleen cells with osteoblastic cells revealed that YM175 was effective when it was present at an early phase of the culture period. Consistent with this observation, YM175 in the presence of osteoblastic cells inhibited proliferation of preosteoclastic cells, but did not inhibit the fusion of mononuclear prefusion osteoclasts. In conclusion, the inhibitory effect of YM175 on OCL formation was confirmed in various murine coculture systems, but the effect was dependent on the types of bone-derived cells supporting osteoclastogenesis. The findings suggest that YM175 inhibits osteoclastogenesis by inhibiting the proliferation of osteoclast precursors through its action on supporting cells of osteoblast lineage rather than acting directly on osteoclast precursors. |
| Databáze: | OpenAIRE |
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