Adenoviral down-regulation of osteopontin inhibits human osteoclast differentiation in vitro
| Autor: | Geoffrey C. Nicholson, Jason M. Hodge, C. J. Aitken |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
musculoskeletal diseases
Sialoglycoproteins Genetic Vectors Down-Regulation Osteoclasts Biochemistry Adenoviridae Mice stomatognathic system Downregulation and upregulation In vivo Osteoclast medicine Animals Humans Secretion Osteopontin Molecular Biology Cells Cultured Membrane Glycoproteins biology Receptor Activator of Nuclear Factor-kappa B Chemistry RANK Ligand Gene Transfer Techniques Cell Differentiation Cell Biology Oligonucleotides Antisense In vitro Resorption medicine.anatomical_structure RANKL Immunology Cancer research biology.protein Carrier Proteins |
| Zdroj: | Journal of cellular biochemistry. 93(5) |
| ISSN: | 0730-2312 |
| Popis: | Although osteopontin (OPN) is highly expressed in osteoclasts, OPN-deficient mice have a near-normal bone phenotype and its role in osteoclast differentiation and function remains uncertain. We used an adenoviral OPN-antisense vector (AdOPN-AS) to down-regulate OPN expression in a human in vitro osteoclastogenesis model employing CFU-GM precursors treated with RANKL and M-CSF. Cultures infected with AdOPN-AS showed reduced secretion of OPN compared to cultures infected with a control adenoviral vector expressing beta-galactosidase. Infection with AdOPN-AS co-incident with exposure to RANKL was associated with substantial (approximately 50%) inhibition of osteoclast formation with a concomitant reduction in dentine resorption. There was also a small reduction in the size of generated osteoclasts but no significant effect on the size of resorption pits/tracks nor on the amount of resorption per osteoclast. When the cultures were infected with AdOPN-AS after 4 days exposure to RANKL only minor effects on osteoclastogenesis were seen. Our data demonstrate that early down-regulation of OPN in vitro inhibits human osteoclastogenesis. Since mice totally lacking OPN do not have reduced osteoclast numbers our results imply the existence in vivo of an alternative molecular pathway(s). |
| Databáze: | OpenAIRE |
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