RANKL (receptor activator of NF-κ B ligand) is a member of the tumor necrosis factor (TNF) superfamily. It is also called also known as TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and ODF (osteoclast differentiation factor).
RANKL is a cell membrane-bound ligand on osteoblasts and activated T cells. It binds RANK on osteblasts precursors, which causes the osteoblast to differentiate and become activated. Osteoprotegrin (OPG) is a soluble, secreted member of the TNF receptor family that competitively binds RANKL and prevents its binding to RANK, thus inhibiting osteoclastogenesis.
Expression of RANKL on osteoblasts is stimulated through
- Vitamin D receptor (1,25 OH vitamin D3)
- Protein kinase A (PGE2, parathyroid hormone)
- gp 130 (IL-11)
The periarticular osteoporosis seen on radiographs of individuals with inflammatory arthritis may be through local production of PGE2 and interleukins (TNFα, Il-1), causing up regulation of RANKL on osteoblasts and T cells leading to osteoclast activation.
