RANK

The nuclear factor kappa B (NFkB) is a ubiquitous transcription factor essential for the activation of immune and inflammatory responses. NFkB activity is inhibited when it is associated with IkB proteins in the cell cytoplasm. IkB proteins are phosphorylated by the IkB kinase complex. The IKK serine protein kinase consists of alpha and beta subunits (IKK alpha and IKK beta). These subunits interact with each other and together, are essential for NFkB activation. IKK alpha is expressed in variety of human tissues.

Osteoprotegerin (OPG) is a secretory glycoprotein that is a family member of the TNF receptor (TNFR) superfamily. Osteoprotegerin protects bone by blocking osteoclastogenesis and increasing bone density. Unlike other TNFRs, osteoprotegerin lacks a transmembrane domain as well as any apparent cell-associated signals. High levels of osteoprotegerin mRNA are found in specialized tissues such as lung, heart, kidney, and placenta. There is evidence that osteoprotegerin plays a role in degenerative arterial disease.

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.

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.