Minireview: The OPG/RANKL/RANK System
2001/12/01 by Sundeep Khosla · 1,414 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Activator (genetics) #Biology #Bone Metabolism and Diseases #Bone health and osteoporosis research #Bone health and treatments #Bone remodeling #Bone resorption #Cell biology #Chemistry #Endocrinology #Internal medicine #Mediator #Medicine #Osteoclast #Osteoporosis #Osteoprotegerin #RANK Ligand #RANKL #Receptor #Stromal cell
paper · pdf · doi:10.1210/endo.142.12.8536
published in Endocrinology 142(12), 5050-5055 (Oxford University Press)
openalex publication_date 2001/12/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04
Abstract
The identification of the OPG/RANKL/RANK system as the dominant, final mediator of osteoclastogenesis represents a major advance in bone biology. It ended a long-standing search for the specific factor produced by preosteoblastic/stromal cells that was both necessary and sufficient for osteoclast development. The initial cloning and characterization of OPG as a soluble, decoy receptor belonging to the TNF receptor superfamily was the first step that eventually led to an unraveling of this system. Soon thereafter, the molecule blocked by OPG, initially called OPG-ligand/osteoclast differentiating factor (ODF) and subsequently RANKL, was identified as the key mediator of osteoclastogenesis in both a membrane-bound form expressed on preosteoblastic/stromal cells as well as a soluble form. RANKL, in turn, was shown to bind its receptor, RANK, on osteoclast lineage cells. The decisive role played by these factors in regulating bone metabolism was demonstrated by the findings of extremes of skeletal phenotypes (osteoporosis vs. osteopetrosis) in mice with altered expression of these molecules. Over the past several years, work has focused on identifying the factors regulating this system, the signaling mechanisms involved in the RANKL/RANK pathway, and finally, potential alterations in this system in metabolic bone disorders, from the extremely common (i.e. postmenopausal osteoporosis) to the rare (i.e. familial expansile osteolysis).
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