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Expression and function of RANK in human monocyte chemotaxis
Birgit A Mosheimer1, Nicole C Kaneider, Clemes Feistritzer
1University of Innsbruck, Innsbruck, Austria.
Arthritis and Rheumatism
|July 13, 2004
Summary
Receptor activator of nuclear factor-kappa B ligand (RANKL) stimulates monocyte migration by activating RANK. This process involves key signaling enzymes, indicating a novel role for RANKL in monocyte chemotaxis.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Receptor activator of nuclear factor-kappa B ligand (RANKL) is crucial for osteoclast function.
- The role of RANKL in monocyte migration and its underlying signaling pathways are not fully understood.
Purpose of the Study:
- To investigate the effect of RANKL on monocyte locomotion in vitro.
- To identify the specific signaling pathways involved in RANKL-mediated monocyte migration.
Main Methods:
- Monocytes were isolated from healthy donors.
- Cell migration was assessed using micropore filter assays.
- Signaling pathways were analyzed using enzyme inhibitors and Western blot; RANK expression was confirmed via RT-PCR and flow cytometry.
Main Results:
- RANKL significantly enhanced monocyte chemotaxis.
- This migration was dependent on the activation of phosphatidylinositol 3-kinase, phosphodiesterase, and Src kinase.
- Osteoprotegerin effectively inhibited RANKL-induced migration, and RANK expression was confirmed on monocyte surfaces.
Conclusions:
- Monocytes express the RANK receptor.
- RANKL activation of monocytes stimulates directed migration.
- The migration involves the phosphatidylinositol 3-kinase, phosphodiesterase, and Src kinase signaling pathways.