IMR Press / FBL / Volume 16 / Issue 1 / DOI: 10.2741/3673

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Regulatory mechanism of osteoclastogenesis by RANKL and Wnt signals
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1 Institute for Oral Science, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano 399-0781, Japan. takahashinao@po.mdu.ac.jp
2 Department of Periodontology, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano 399-0781, Japan
3 Department of Biochemistry, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano 399-0781, Japan
4 Department of Orthopaedic Surgery, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan
Academic Editor:Masato Tamura
Front. Biosci. (Landmark Ed) 2011, 16(1), 21–30; https://doi.org/10.2741/3673
Published: 1 January 2011
(This article belongs to the Special Issue Molecular mechanism in bone cells)
Abstract

Osteoclasts develop from monocyte-macrophage lineage cells under the regulation of osteoblasts. Osteoblasts express two cytokines essential for osteoclastogenesis, macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-KappaB ligand (RANKL). Osteoblasts also produce osteoprotegerin (OPG), a decoy receptor for RANKL, which inhibits the interaction between RANKL and RANK, a receptor of RANKL. Bone resorption-stimulating factors act on osteoblasts to regulate RANKL and OPG expression. Nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) is a master transcription factor for osteoclast differentiation. The immunoreceptor tyrosine-based activation motif (ITAM)-mediated signal was discovered as a co-stimulatory signal in RANKL-induced osteoclastogenesis. Wnt proteins activate two pathways: beta-catenin-dependent canonical and beta-catenin-independent noncanonical pathways. Wnt proteins promote differentiation of osteoblasts through the canonical pathway. The canonical pathway in osteoblasts also suppresses osteoclastogenesis through up-regulation of OPG expression and down-regulation of RANKL expression. In contrast, activation of the noncanonical pathway in osteoclast precursors enhances RANKL-induced osteoclastic differentiation. Thus, Wnt signals in osteoblasts and osteoclast precursors play important roles in osteoclastogenesis. This review summarizes the regulatory mechanism of osteoclastogenesis by RANKL and Wnt signals.

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