c-myc Is Required for Osteoclast Differentiation
| Autor: | Fu Xy, Ricardo A. Battaglino, Fu J, Philip Stashenko, Vaage B, Dae Hyun Kim |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty Endocrinology Diabetes and Metabolism Cellular differentiation Genes myc Gene Expression Osteoclasts Biology Transfection Monocytes Cell Line Proto-Oncogene Proteins c-myc Mice Osteogenesis Osteoclast Internal medicine Gene expression medicine Animals Orthopedics and Sports Medicine Northern blot Transcription factor TNF Receptor-Associated Factor 6 Cathepsin Membrane Glycoproteins Receptor Activator of Nuclear Factor-kappa B Basic Helix-Loop-Helix Leucine Zipper Transcription Factors RANK Ligand Proteins Cell Differentiation Cell biology DNA-Binding Proteins Repressor Proteins Basic-Leucine Zipper Transcription Factors Endocrinology medicine.anatomical_structure RANKL biology.protein Carrier Proteins Transcription Factors |
| Zdroj: | Journal of Bone and Mineral Research. 17:763-773 |
| ISSN: | 0884-0431 |
| Popis: | The role of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL)-a tumor necrosis factor (TNF)-related cytokine-in osteoclast formation has been established clearly. However, the downstream signaling pathways activated by this cytokine remain largely unknown. To identify genes that play a role in osteoclastogenesis, we used RAW 264.7 mouse monocytes as a model system for the differentiation of multinucleated osteoclasts from mononucleated precursors. RAW 264.7 cells were induced with RANKL to form multinucleated giant osteoclast-like cells (OCLs) that expressed a number of osteoclast-specific markers and were able to form resorption pits on both calcium phosphate films and bone slices. This system was used to identify genes that are regulated by RANKL and may play a role in osteoclast differentiation. The proto-oncogene c-myc was strongly up-regulated in RANKL-induced OCLs but was absent in undifferentiated cells. Expression of Myc partners Max and Mad, on the other hand, was constant during OCL differentiation. We expressed a dominant negative Myc in RAW 264.7 cells and were able to block RANKL-induced OCL formation. Northern Blot analysis revealed a delay and a significant reduction in the level of messenger RNA (mRNA) for tartrate-resistant acid phosphatase (TRAP) and cathepsin K. We conclude that c-myc is a downstream target of RANKL and its expression is required for RANKL-induced osteoclastogenesis. |
| Databáze: | OpenAIRE |
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