Peptide Inhibitor May Prevent Bone Loss In Osteoporosis

Two molecules known as RANK and TNFR promote the differentiation of osteoclasts - cells that are responsible for the breakdown of bone. This process occurs in healthy individuals - as part of the constant renewal of the bone that makes up our skeleton, and it occurs at an increased rate in individuals with diseases such as osteoporosis, rheumatoid arthritis, and periodontal disease. A site on TNFR that is critical for the binding of activating molecules is also conserved, in part, on RANK. In a study appearing online in May, in advance of print publication in the June issue of the Journal of Clinical Investigation, Roland Baron and colleagues from Yale University School of Medicine show that mimicking a critical loop of TNFR and RANK with a small cyclic peptide allows the inhibition of RANK ligandвЂ"induced bone breakdown and resorption in mouse models of osteoporosis. The authors used molecular modeling to demonstrate the exact region where the peptide binds and interferes with RANK signaling. These findings pave the way for the development of new strategies for designing peptide as well as nonpeptide inhibitors of RANK ligand-induced osteoclast-mediated bone loss, which is a key pathway in the mechanisms at work in many bone and joint diseases.



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TITLE: A TNF receptor loop peptide mimic blocks RANK ligandвЂ"induced signaling, bone resorption, and bone loss



Highlights from the Journal of Clinical Investigation



AUTHOR CONTACT:

Roland Baron

Yale University School of Medicine, New Haven, Connecticut, USA.



View the PDF of this article at: https://the-jci/article.php?id=22513



Contact: Brooke Grindlinger

Journal of Clinical Investigation