RANK ligand
| RANK ligand | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 317 amino acids (receptor); 178 amino acids (soluble form) | |
| Secondary to quaternary structure | Homotrimer | |
| Isoforms | 3 | |
| Identifier | ||
| Gene name | TNFSF11 | |
| External IDs | ||
| Occurrence | ||
| Parent taxon | Terrestrial vertebrates | |
RANKL (short for " R preceptor A ctivator of N F κ B L igand") is a 1997 discovered protein from the family of tumor necrosis factor (TNF), which essentially on the regulation of bone remodeling is involved. The protein is also known under the names TRANCE (TNF-related activation-induced cytokine), CD254, OPGL and ODF. RANKL will u. a. secreted by osteoblasts (cells that build up bone substance) and binds to the "matching" receptor RANK of monocytic osteoclast precursor cells, which causes their differentiation into osteoclasts (cells that break down bone substance again). The RANK / RANKL system is a biochemical control circuit that ensures that bone loss and bone structure remain in a healthy balance, which is a prerequisite for the dynamic architecture of the bone system. This system can be disturbed in various diseases and is therefore of practical interest for medicine. The monoclonal antibody denosumab is an antibody against RANKL and can be used in diseases associated with overactive osteoclasts (e.g. osteoporosis or rheumatoid arthritis ).
regulation
RANKL can be antagonized by osteoprotegerin (OPG), which is also secreted by osteoblasts . OPG works as a so-called capture receptor for RANKL, which thus does not come into contact with the special receptor RANK on the osteoclast progenitor cell surface. The osteoblasts themselves counteract osteoclast differentiation via the RANKL path through the production of osteoprotegerin. This balance is regulated as follows:
- 1.25 (OH) 2 VitD 3 : The 1.25 (OH) 2 D 3 - VDR complex in the osteoblasts increases the formation of RANKL and suppresses the formation of OPG and thus promotes bone resorption. Under conditions of the (often present) vitamin D deficiency, this effect is not relevant, as vitamin D also suppresses the parathyroid hormone and ensures a good supply of calcium and phosphate to the body , i.e. it has an indirect bone strengthening effect. The bone-degrading effect of the 1,25 (OH) 2 D 3 - VDR complex can be suppressed by vitamin K 2 , so that osteoporosis therapy with vitamin D can be supported by vitamin K 2 .
- Estrogens are described as another natural suppressor from RANKL . This explains the frequency of osteoporosis in postmenopausal women, as the natural suppressor of osteoclast differentiation (estrogen) is no longer available in sufficient quantities.
- RANKL can be secreted in an unregulated manner by tumor cells, which causes increased bone loss due to the tumor.
- In many cases, synthetic progesterones are responsible for the development of breast cancer. Research from 2010 showed that RANKL is a crucial factor in this chain. Studies in mice have shown that inactivating the RANKL gene leads to a significant reduction in breast cancer.
Individual evidence
- ↑ Homologues at OMA
- ↑ Keck AV, Pecherstorfer M: Bone metabolism in malignant diseases . Journal for Mineral Metabolism (2003) 10: 6-11. online (PDF; 1.9 MB) , accessed on May 1, 2007.
- ↑ Dusso, AS et al. (2005): Vitamin D ( Memento of the original from May 15, 2007 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. . Am J Physiol Renal Physiol 289: F8-F28.
- ↑ SM Plaza, DW Lamson: Vitamin K2 in bone metabolism and osteoporosis. In: Alternative medicine review: a journal of clinical therapeutic. Volume 10, Number 1, March 2005, pp. 24-35, PMID 15771560 (review).
- ↑ How hormones can trigger breast cancer Medical University of Vienna
