RANKL (also known as TNF-related activation-induced cytokine), or receptor activator of nuclear factor-κB ligand, was first discovered as a key player in the RANKL/RANK/OPG osteoclast formation pathway. Osteoclasts are large multinucleate cells that absorb bone tissue throughout growth and healing cycles. Osteoclasts express RANKL, which in turn binds to the RANK receptor to regulate osteoclast differentiation. In healthy bone formation, dynamics shift between new bone formation and existing bone reabsorption, resulting in an important equilibrium that results in osteoporosis or other bone pathologies if disrupted. Specifically, overstimulation of RANKL activity has been linked to osteoporosis, osteopetrosis, arthritis and additional bone malignancies.
In the presence of Recombinant Mouse M-CSF (20 ng/mL, Catalog # 416-ML), Recombinant Mouse TRANCE/TNFSF11/RANK L (Catalog # 462-TR) induces osteoclast-like cell formation in mouse splenocytes in a dose-dependent manner (orange line), as measured by TRAP (tartrate-resistant acid phosphatase) solution assay. Under these conditions, osteoclast-like cell formation elicited by Recombinant Mouse TRANCE/TNFSF11/RANK L (30 ng/mL) is neutralized (green line) by increasing concentrations of Goat Anti-Mouse TRANCE/TNFSF11/RANK L Antigen Affinity-purified Polyclonal Antibody (Catalog # AF462). The ND50 is typically 0.02-0.06 µg/mL.
While RANKL is primarily known for its role in osteoclast regeneration and formation, it has also been implicated in both innate immune response and mammary gland structure. Schramek et al used a RANKL antibody (Cat# AF462) to show that RANKL controls the development of progestin-driven mammary cancer. This group first used the RANKL antibody to establish that the progesterone derivative MPA induced RANKL expression in mammary epithelial cells. Leibbrandt et al set out to establish novel functions of RANKL in the immune system. Their group used primary antibodies and knockout mice to show that the RANKL-RANK-OPG pathway is involved in processes outside of bone growth, specifically in controlling immune response in the skin. Interestingly enough, their work highlighted the ability for immune cells and bone to crosstalk, and strengthened predetermine studies that observed bone loss in patients with overly activated immune responses. To continue to elucidate function of RANKL in bone and immune response, Lubberts et al used a RANKL antibody (Cat# AF462) in immunohistochemistry to show that the t-cell derived inflammatory pro cytokine IL-17 promotes bone erosion in arthritis through a loss of RANKL/OPG balance. Specifically, over activation of IL-17 in turn threw off the balance of the RANKL/OPG system, in turn resulting in collagen-induced arthritis.
Through analysis of all of these different research topics, there is a clear diverse function of RANKL in immune response, mammary gland formation and bone disease. Using RANKL and associated antibodies help to further elucidate the role of this protein in each section of research, whether it is used as a baseline control or a method of discovering new key players in these pathways.
Novus Biologicals offers TRANCE/TNFSF11/RANK L reagents for your research needs including:
