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The Effects of Receptor Activator of NF-κB Ligand-Binding Peptides on Bone Resorption and Bone Formation

Authors
  • Rashed, Fatma1, 2
  • Kamijyo, Shingo1
  • Shimizu, Yuri1
  • Hirohashi, Yuna1
  • Khan, Masud1
  • Sugamori, Yasutaka3
  • Murali, Ramachandran4
  • Aoki, Kazuhiro1
  • 1 Graduate School of Medical and Dental Sciences, Institute X, Department of Basic Oral Health Engineering, Tokyo Medical and Dental University, Tokyo , (Japan)
  • 2 Department of Oral Biology, Faculty of Dentistry, Damanhour University, El Behera , (Egypt)
  • 3 Department of Dentistry and Oral Surgery, Saitama Medical University, Saitama , (Japan)
  • 4 Biomedical Sciences, Research Division of Immunology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA , (United States)
Type
Published Article
Journal
Frontiers in Cell and Developmental Biology
Publisher
Frontiers Media SA
Publication Date
Jul 06, 2021
Volume
9
Identifiers
DOI: 10.3389/fcell.2021.648084
Source
Frontiers
Keywords
Disciplines
  • Cell and Developmental Biology
  • Mini Review
License
Green

Abstract

Receptor activator of NF-κB ligand (RANKL)-binding peptides inhibit bone resorption and were recently shown to activate bone formation. The stimulatory mechanism underlying bone formation associated with these peptides was explained as RANKL-reverse signaling, wherein RANKL molecules on osteoblasts work as receptors to stimulate osteoblast differentiation. However, why RANKL-binding peptides stimulate osteoblast differentiation while osteoprotegerin (OPG), which is well known to bind to RANKL, cannot activate osteoblast differentiation has remained unclear. In this mini-review, we introduce three main issues: (1) The inhibitory effects of two RANKL-binding peptides (W9 and OP3-4) on bone resorption; (2) The stimulatory effects of the RANKL-binding peptides on osteoblast differentiation; and (3) The accumulation and membrane clustering of RANKL molecules at the cell surface of osteoblasts as a potential molecular switch stimulating osteoblast differentiation by RANKL-binding peptides.

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