Tnfsf11

What is TNFSF11 Protein?

TNFSF11 gene (TNF superfamily member 11) is a protein coding gene which situated on the long arm of chromosome 13 at locus 13q14. This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. The TNFSF11 protein is consisted of 317 amino acids and TNFSF11 molecular weight is approximately 35.5 kDa.

What is the Function of TNFSF11 Protein?

TNFSF11, also known as RANKL, is mainly involved in the differentiation and activation of osteoclasts as a key factor, and is an important regulator in the process of bone resorption. RANKL binds to its receptor RANK and activates a variety of signaling pathways, leading to osteoclast-specific gene transcription, thereby promoting osteoclast maturation and functional performance. In addition, RANKL enhances the ability of dendritic cells to stimulate naive T cell proliferation and may play an important role in the regulation of T-cell-dependent immune responses. In addition, RANKL expression is regulated by cell type-specific distal enhancers, and in T cells, this regulation is achieved by multiple distal elements

Fig1. B cells and T cells are primary RANKL expression cells in periodontal bone resorption. (Bin Chen, 2014)

TNFSF11 Related Signaling Pathway

RANKL binds to its receptor RANK and activates the NF-κB signaling pathway. This pathway mainly controls the processes of cell proliferation, differentiation and immune response. RANKL can also influence cell survival and death by activating mitogen-activated protein kinase (MAPK) signaling pathways, such as inducing apoptosis or necrosis. RANKL is a key factor in osteoclast formation. By binding with RANK, it promotes the differentiation and maturation of osteoclasts, thus affecting bone resorption. RANKL-RANK signaling is essential for maintaining bone health and function. RANKL can also promote apoptosis and necrosis of cells, typically through the formation of cytoplasmic complex II, which involves dissociation of TRADD from complex I, and recruitment of FADD and procaspase-8, leading to caspase-8 activation and apoptosis induction.

TNFSF11 Related Diseases

Abnormal functioning of TNFSF11 (RANKL) is associated with a variety of diseases, especially bone-related diseases such as osteoporosis, which lead to increased bone resorption by affecting osteoclast differentiation and activity; Osteosclerosis, reduced bone formation due to loss of RANKL function; As well as some autoimmune diseases, in which RANKL is involved in regulating the activity of immune cells, dysregulation of which can lead to inflammatory responses and tissue damage. In addition, abnormal activation of RANKL signaling pathway is also associated with the occurrence and development of some cancers.

Bioapplications of TNFSF11

TNFSF11 (RANKL), as a key signaling molecule, has a wide range of applications in medicine and biotechnology, especially in the treatment of osteoporosis, where the use of RANKL inhibitors such as Denosumab can effectively slow bone resorption, increase bone mineral density and reduce the risk of fracture. At the same time, RANKL's role in promoting osteoblast differentiation and bone formation also makes it a potential application value in fracture healing, bone defect repair and tissue engineering. In addition, RANKL's function in immune regulation also allows it to play a role in the treatment of certain autoimmune diseases, by regulating the RANKL-RANK signaling pathway, it can control the inflammatory response and the activity of immune cells.