OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis

Abstract

The tumour-necrosis-factor-family molecule osteoprotegerin ligand (OPGL; also known as TRANCE, RANKL and ODF) has been identified as a potential osteoclast differentiation factor and regulator of interactions between T cells and dendritic cells in vitro. Mice with a disrupted opgl gene show severe osteopetrosis and a defect in tooth eruption, and completely lack osteoclasts as a result of an inability of osteoblasts to support osteoclastogenesis. Although dendritic cells appear normal, opgl-deficient mice exhibit defects in early differentiation of T and B lymphocytes. Surprisingly, opgl-deficient mice lack all lymph nodes but have normal splenic structure and Peyer's patches. Thus OPGL is a new regulator of lymph-node organogenesis and lymphocyte development and is an essential osteoclast differentiation factor in vivo.

The pathogenesis of the bone disease of multiple myeloma

“…The interaction between RANKL and RANK is critical in the formation and activation of osteoclasts, and inhibition by OPG results in inhibition of bone resorption. The critical role of these TNF family members is highlighted by in vivo studies where mice deficient in RANK or RANKL have extensive osteopetrosis due to a lack of functional osteoclasts (17,18), whereas OPG knock out mice have severe osteoporosis (19).…”

The RANK/RANKL/osteoprotegerin system in rheumatoid arthritis: New insights from animal models

“…RANKL-or RANKdeficient mice show abnormal development of B cells and thymocytes, as well as inappropriate responsiveness of T cells stimulated by DCs (16,36). A study in healthy human volunteers revealed that activated T cells express RANKL and thereby induce the formation of osteoclastlike cells from peripheral blood mononuclear cells (37).…”

“…RANKL (also known as OPG ligand or osteoclast differentiation factor) is a membranespanning 38-kd protein that consists of 316 amino acids and belongs to the TNF superfamily. Three RANKL subunits form the functional molecule, which is anchored to the cell membrane and can be released from the cell after cleavage by the metalloproteinase disintegrin TNF␣ convertase (15,16). RANKL is highly expressed by osteoblasts, osteoclasts, endothelial cells, stromal cells, primitive mesenchymal cells surrounding the cartilage, and chondrocytes (8).…”

“…RANKL binds specifically and with high affinity to OPG. Therefore, OPG effectively inhibits osteoclast maturation and osteoclast activation by inhibiting RANK-RANKL interactions (16,30).…”

RANKL acts directly on RANK‐expressing prostate tumor cells and mediates migration and expression of tumor metastasis genes

“…The TNF ligand superfamily member RANKL is critical for formation, function, and survival of osteoclasts [10,11] and exerts its action through binding and activation of its receptor RANK [12,13], which is expressed on the surface of myeloid osteoclast precursors [14]. Osteprotegerin (OPG) is a soluble member of the TNF receptor super family secreted by osteoblasts which, by competing with RANK for RANKL, acts as a decoy receptor of RANKL, thereby inhibiting osteoclastogenesis.…”