title: Regulatory mechanism of osteoclastogenesis by RANKL and Wnt signals.
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.
authors.affiliation: Institute for Oral Science, Matsumoto Dental University, 1780 Gobara, Hiro-oka, Shiojiri, Nagano 399-0781, Japan. takahashinao@po.mdu.ac.jp
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Maeda
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishihara
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Uehara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology; D002454:Cell Differentiation; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology; D050778:NFATC Transcription Factors / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D053245:RANK Ligand / Q000502:physiology*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501589:DCSTAMP protein, human; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D053245:RANK Ligand; D051153:Wnt Proteins; D016173:Macrophage Colony-Stimulating Factor