Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation

Abstract

The ligand for osteoprotegerin has been identified, and it is a TNF-related cytokine that replaces the requirement for stromal cells, vitamin D3, and glucocorticoids in the coculture model of in vitro osteoclastogenesis. OPG ligand (OPGL) binds to a unique hematopoeitic progenitor cell that is committed to the osteoclast lineage and stimulates the rapid induction of genes that typify osteoclast development. OPGL directly activates isolated mature osteoclasts in vitro, and short-term administration into normal adult mice results in osteoclast activation associated with systemic hypercalcemia. These data suggest that OPGL is an osteoclast differentiation and activation factor. The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGL and OPG are key extracellular regulators of osteoclast development.

Graphene‐Based MicroRNA Transfection Blocks Preosteoclast Fusion to Increase Bone Formation and Vascularization

“…Mature osteoclasts are bone‐specific polykaryons derived from multipotent hematopoietic stem cells and differentiated from monocyte/macrophage precursor cells near the bone surface 1. Two important regulating factors, receptor activator of nuclear factor κB ligand (RANKL) and macrophage‐colony stimulating factor (M‐CSF) are necessary for OC differentiation and survival 2. Dysregulation of osteoclastogenesis can lead to various bone disorders and the most common one is osteoporosis 3, 4.…”

The pathogenesis of the bone disease of multiple myeloma

“…RANKL is expressed on the surface of osteoblasts and bone marrow stromal cells and the interaction between RANKL and its signalling receptor RANK, found on the surface of osteoclast precursor cells, stimulates osteoclast formation and bone resorption (14,15) (15). OPG is a soluble decoy receptor which is secreted by bone marrow stromal cells and osteoblasts, and binds to RANKL, preventing its interaction with its cognate receptor RANK (16).…”

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

“…Osteoblasts differentiate from mesenchymal stem cells, while osteoclasts originate from hematopoietic monocyte/ macrophage precursors (4-7). The receptor activator of NF-B (RANK)/RANKL system has been identified as an important factor in osteoclast cell differentiation and bone resorption (8)(9)(10). In addition, osteoprotegerin (OPG) functions as a high-affinity soluble decoy receptor for RANKL and competes with RANK for RANKL binding.…”