TNF-family member Receptor Activator of NF-$B (RANK) and RANK-Ligand (RANKL) in bone remodelling

WJ Quax, AHG van Assen, Yizhou Wang

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Abstract

Receptor Activator of NF-κB (RANK) and RANK-Ligand (RANKL) are members of the Tumour Necrosis Factor (TNF)-superfamily involved in bone homeostasis. In a tightly controlled interplay of this receptor and ligand, bone is continuously being remodelled. Several pathological conditions resulting from a misbalance between bone resorption and bone formation have been documented. Most frequently resorption gets the overhand resulting in a lower Bone Mineral Density (BMD), increased fracture risk and reduced mobility of patients. RANKL is expressed on bone producing osteoblasts whereas RANK is expressed on preosteoclasts, which can develop in bone resorbing osteoclasts. The binding of RANKL to RANK functions as a trigger for the formation of these bone resorbing osteoclasts. With the development of a monoclonal antibody directed against RANKL a new therapeutic strategy to interfere with bone remodelling has become available some years ago. In this manuscript we discuss the prospective of interfering with the RANK/RANKL pathway as a therapeutic target for bone diseases. We discuss the role of the soluble receptor osteoprotegerin (OPG) as a therapeutic in bone diseases. Then we focus on the possibility to develop antagonistic and agonistic variants of RANKL based on computational protein design and we discuss the development of antagonistic RANKL variants by changing the stoichiometry of the RANKL molecule.
Original languageEnglish
Title of host publicationIOP Conference Series: Earth and Environmental Science
PublisherIOP PUBLISHING LTD
Number of pages9
DOIs
Publication statusPublished - 2018

Publication series

Name IOP Conference Series: Earth and Environmental Science Paper • The following article is OPEN ACCESS TNF-family member Receptor Activator of NF-κB (RANK) and RANK-Ligand (RANKL) in bone remodelling W J Quax, A H G van Assen and Y Z Wang Published under licence by IOP Publishing Ltd IOP Conference Series: Earth and Environmental Science, Volume 185, conference 1
PublisherIOP Publishing
Number1
Volume185
ISSN (Print)1755-1307
ISSN (Electronic)1755-1315

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