RANK and RANKL: Climbing the Ranks of Bone Metabolism

Thu, 03/13/2014 - 10:40

Apoptosis, or programmed cell death, is a normal component of cellular differentiation and the development of multicellular organisms. Receptor activator of NF-kB (RANK) lacks significant homology with the other family members of the tumor necrosis factor receptor (TNFR) superfamily. The cytoplasmic domain of RANK interacts with the tumor necrosis factor receptor associated factors, adaptor proteins such as TRAF2, TRAF5 and TRAF6. Overexpression of RANK activates NF-kB and c-Jun-terminal kinase (JNK) pathways. RANK and RANKL signaling is well characterized in the bone remodeling system and both are key players in osteoclast activity and induction. Riegel’s group used the RANK antibody to characterize the expression and localization patterns of RANK in polymorphonuclear neutrophils (PMNs) in response to inflammation1.  Additionally, RANK antibody was employed in bone remodeling studies in the same polymorphonuclear neutrophil (PMNs) model to provide evidence for their model that elevated circulating follicle-stimulating hormone (FSH) levels contribute to increased bone loss through the development of osteoclast precursors 2.

Western Blot: RANK Antibody Western Blot: RANK Antibody

Studies in Fiumara‘s lab with the RANK antibody showed functional similarities between dendritic cells (DCs) and Hodgkin Reed-Sternberg cells (H/RS cells) of Hodgkin’s Disease3. They believe that RANK and RANKL regulate cytokine and chemokine production in H/RS cells in an autocrine manner. The structure-function characterization of various RANK signal peptide mutants was performed in HEK293 cells with the RANK antibody, with results indicating that, as anticipated, the lack of signal peptide cleavage results in intracellular deposition of RANK to the endoplasmic reticulum, thus blocking the RANKL activation pathway4.  Huang et al used immunoblotting with the RANK antibody to validate a novel and reliable cloning method from templates containing high-GC content-rich areas5. The RANK gene was chosen as a hallmark system of such a difficult template, and subjected to cloning using a splicing by overlapping extension-PCR (SOE-PCR) method that was ultimately proven to be both feasible and universally applicable.

  1. 22531921
  2. 21159522
  3. 11675352
  4. 21472776
  5. 21660576

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