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Osteoclastogenesis: Roles of Filamin A and SBDS, and their Regulation of Rho GTPases during Pre-osteoclast Migration

Osteoclasts are multinucleated, bone resorbing cells that carry out their function using specialized actin-based structures called actin rings and podosomes. Rho GTPases function as molecular switches that regulate the actin cytoskeleton in osteoclasts and many other cell types. Filamin A (FLNa) and SBDS are two proteins that have the potential to interact with both F-actin and Rho GTPases, and thus regulate osteoclast formation, differentiation, or function. We found that in FLNa-null pre-osteoclasts, activation of RhoA, Rac1, and Cdc42 was perturbed, leading to defective pre-osteoclast migration prior to fusion. Ablation of SBDS resulted in the blockage of osteoclast differentiation downstream of RANK and defective RANKL-mediated upregulation of Rac2 that is required for pre-osteoclast migration. Therefore, both FLNa and SBDS are required to coordinate Rho GTPase activation during osteoclastogenesis, in addition to a role for SBDS in osteoclast differentiation downstream of RANK.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/34782
Date17 December 2012
CreatorsLeung, Roland
ContributorsGlogauer, Michael
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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