The intricate processes of osteoclastogenesis are highly dependent on the dynamic regulation of the actin cytoskeleton. Adseverin, a member of the gelsolin superfamily of actin binding proteins, regulates actin remodeling by severing and capping actin filaments in a calcium dependent manner. The objective of this project was to characterize the role(s) of adseverin during osteoclastogenesis, by assessing adseverin expression throughout osteoclastogenesis and through differentiation assays using a knockdown strategy. Methods: qRT-PCR and immunoblot analyses were used to examine adseverin expression during osteoclastogenesis. A stable adseverin knockdown macrophage cell line was generated using a retroviral shRNA construct. Results: Adseverin expression increased significantly in response to RANKL during the early phases of osteoclastogenesis, and adseverin was highly expressed in mature osteoclasts. Adseverin knockdown macrophages experienced a major osteoclastogenesis defect, most likely caused by a defect in pre-osteoclast fusion. Conclusion: Adseverin is a RANKL induced early and pro-fusion marker of osteoclastogenesis.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/25614 |
| Date | 01 January 2011 |
| Creators | Hassanpour, Siavash |
| Contributors | Glogauer, Michael |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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