Pulling RANK: Immune Response and Osteoclast Activation by RANKL

Fri, 02/21/2014 - 11:00

RANKL is the ligand for the receptor activator of NFkB (RANK) that belongs to the tumor necrosis factor receptor (TNFR) superfamily. RANK overexpression induces the NFkB and c-Jun-terminal kinase (JNK) downstream pathways. This pathway has been studied in detail in the bone remodeling system with regards to osteoclast activity and induction. The RANK antibody was used to characterize the expression and localization patterns of RANK in polymorphonuclear neutrophils (PMNs) upon inflammation (1).  Additionally, RANKL antibody was employed in bone remodeling studies on a mouse osteoblast model to investigate the role of osteoclast differentiation factor (ODF) in lipopolysaccharide (LPS)-mediated bone diseases such as periodontitis (2). Those researchers used RANKL antibody to demonstrate that LPS directly induces ODF mRNA via Toll-like receptors (TLRs). In RANK antibody immunoblots, Fiumara‘s lab used dendritic cells (DCs) and Hodgkin Reed-Sternberg cells (H/RS cells) of Hodgkin’s Disease to probe for functional similarities between the two cell populations (3).

Immunohistochemistry-Paraffin: RANKL Antibody Immunohistochemistry-Paraffin: RANKL Antibody

Their data suggests that RANK and RANKL regulation of both cytokine and chemokine production in the H/RS cells is through an autocrine mechanism. Hsu, et al. characterized the signal components downstream of osteoprotegerin ligand (OPGL) in transgenic mice with the RANK antibody, and found that the resulting osteoclastogenesis in osteoclast progenitor cells is RANK-mediated (4).  Some recent prostate cancer studies from Rubin’s group suggest that tumor-secreted insulin growth factor 1(IGF1) synergizes with the co-existing endogenous pool to allow progression to a metastatic phenotype in prostate cancer (5). The RANK antibody allowed them to validate their prostate cancer progression model comprised of three genetically related human cell lines.

  1. PMID: 22531921
  2. PMID: 11207318
  3. PMID: 11675352
  4. PMID: 14673951

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