[Osteoprotegerin--a neutralizing receptor, protector of bones and a potential antiresorptive agent].
BACKGROUND
The receptor activator of NF-B ligand (RANKL), expressed on the surface of osteoblasts and stromal cells in the bone marrow, plays an essential role in the formation and differentiation of osteoclasts and bone resorption. RANKL binds to its functional receptor, receptor activator of NF-B (RANK), expressed as a transmembrane heterotrimer on the surface of hematopoietic osteoclasts progenitors and mature osteoclasts. RANKL-RANK interaction is inhibited by soluble receptor-osteoprotegerin.
Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor superfamily, acts as a natural decoy receptor that blocks the interaction between RANKL and RANK. The balance between RANKL and osteoprotegerin is of major importance in bone homeostasis. Osteoprotegerin inhibits differentiation and formation of osteoclasts and induces apoptosis of osteoclasts. OPG knock-out mice develop severe osteoporosis. In contrast, overexpression of OPG in transgenic mice causes osteopetrosis.
Antiresorptive activity of osteoprotegerin is proved in numerous experimental models. Osteoprotective effect of osteoprotegerin has recently been proved in postmenopausal women with osteoporosis as well as in patients with multiple myeloma and osteolytic metastases of breast cancer.


CONCLUSIONS
Osteoprotegerin is a potent antiosteoclast agent that may prove useful in the treatment of bone disorders with net bone loss, such as postmenopausal osteoporosis and cancer metastases.
Andelković
Zlatibor
Z
Institut za histologiju i embriologiju, Medicinski fakultet Pristina, Kosovska Mitrovica. zlatibor@bankerinter.net
Katić
Vuka
V
Mihajlović
Dragan
D
Zivković
Vesna
V
Petrović
Aleksandar
A
Lalosević
Dusan
D
D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology; D002352:Carrier Proteins / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology; D010024:Osteoporosis / Q000188:drug therapy; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology* / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology* / Q000627:therapeutic use
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human