Regulatory mechanism of osteoclastogenesis by Wnt signaling

• Kobayashi Yasuhiro

  Institute for Oral Science, Matsumoto Dental University, Nagano, Japan

• Maeda Kazuhiro

  Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan

• Uehara Shunsuke

  Department of Biochemistry, Matsumoto Dental University, Nagano, Japan

• Yamashita Teruhito

  Institute for Oral Science, Matsumoto Dental University, Nagano, Japan

• Takahashi Naoyuki

  Institute for Oral Science, Matsumoto Dental University, Nagano, Japan

Abstract

Bone-resorbing osteoclasts develop from monocyte-macrophage lineage cells under the regulation of bone-forming osteoblasts. Osteoblasts express two cytokines essential for osteoclastogenesis, macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). Osteoblasts also produce osteoprotegerin (OPG), a decoy receptor for RANKL, which inhibits the interaction between RANKL and RANK, a receptor of RANKL. Wnt proteins (Wnts) play a central role in the development of organs and tissues. There are two pathways of Wnt signaling. β-catenin-dependent canonical and β-catenin-independent noncanonical pathways. The discovery that loss-of-function mutations in low density lipoprotein receptor-related protein 5 (LRP5), a Wnt co-receptor, led to low bone mass in humans revealed the possible role of Wnt signaling in bone formation: Wnts act on osteoblast precursor cells and promote their differentiation into osteoblasts through the β-catenin-dependent canonical pathway. In addition, Wnts suppress bone resorption by the up-regulation of OPG expression and the down-regulation of RANKL expression in osteoblasts through the same pathway. In contrast, the activation of the β-catenin-independent noncanonical pathway enhances the RANKL-induced osteoclastogenesis. Recent studies have shown that the β-catenin independent noncanonical pathway is also involved in bone resorption induced by arthritis. This review summarizes the regulatory mechanism of bone resorption by Wnt signals.

Journal

• Inflammation and Regeneration

  Inflammation and Regeneration 31 (5), 413-419, 2011

  The Japanese Society of Inflammation and Regeneration

Keywords

• Osteoclast
• osteoblast
• Wnt
• Ror
• LRP5/6

Details

• CRID: 1390001205257828480
• NII Article ID: 130004943807
• DOI: 10.2492/inflammregen.31.413
• ISSN: 18808190
• ISSN: 18809693
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed