osteoclastogenesis

Osteoprotegerin (OPG, Tnfrsf11b) is a secreted protein that regulates bone density. OPG is widely expressed and constitutively released as a homodimer by mesenchymal stem cells, fibroblasts and endothelial cells. Regulation of its expression by estrogen, parathyroid hormone and cytokines is complex and changes with age. OPG acts as decoy receptor for TNFSF11 RANKL and thereby neutralizes its function in osteoclastogenesis. TRAIL decreases the release of OPG from cells that express it, while OPG inhibits TRAIL-induced apoptosis. Expression of RANK L on the cell surface, and thus its ability to stimulate osteoclastogenesis, is regulated by OPG by intracellular and extracellular mechanisms. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. It may also play a role in preventing arterial calcification.

TNFRSF11B is a secreted protein, containing 2 death domains and 4 TNFR-Cys repeats. TNFRSF11B is a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL). By binding RANKL, TNFRSF11B inhibits nuclear kappa B (NF-κB) which is a central and rapid acting transcription factor for immune-related genes, and a key regulator of inflammation, innate immunity, and cell survival and differentiation. TNFRSF11B levels are influenced by voltage-dependent calcium channelsCav1.2. TNFRSF11B can reduce the production of osteoclasts by inhibiting the differentiation of osteoclast precursors (osteoclasts are related to monocytes macrophages and are derived from granulocyte macrophage-forming colony units (CFU-GM)) into osteoclasts and also regulates the resorption of osteoclasts in vitroand in vivo. TNFRSF11B binding to RANKL on osteoblast stromal cells, blocks the RANKL-RANK ligand interaction between osteoblast stromal cells and osteoclast precursors. This has the effect of inhibiting the differentiation of the osteoclast precursor into a mature osteoclast.

Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione. Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B. Required for normal osteoclastogenesis.

Osteoclast-associated receptor (OSCAR) is a co-stimulatory receptor in osteoclastogenesis. Synovial tissues from active rheumatoid arthritis (RA) patients express higher levels of OSCAR compared with osteoarthritic and normal patients. OSCAR and tartrate-resistant acid phosphatase (TRAP) expression levels did not differ between the cartilage pannus junction (CPJ) and non-CPJ regions in active RA. OSCAR Protein, Mouse, Recombinant (hFc) is expressed in HEK293 mammalian cells with C-hFc tag. The predicted molecular weight is 49.7 kDa and the accession number is Q8VBT3-1.

Osteoclast-associated receptor (OSCAR) is a co-stimulatory receptor in osteoclastogenesis. Synovial tissues from active rheumatoid arthritis (RA) patients express higher levels of OSCAR compared with osteoarthritic and normal patients. OSCAR and tartrate-resistant acid phosphatase (TRAP) expression levels did not differ between the cartilage pannus junction (CPJ) and non-CPJ regions in active RA. OSCAR Protein, Human, Recombinant (hFc) is expressed in HEK293 mammalian cells with C-hFc tag. The predicted molecular weight is 49.8 kDa and the accession number is Q8IYS5-1.

Cytokine that binds to TNFRSF11B OPG and to TNFRSF11A RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy. Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation.