Molecules and Cells

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Fig. 3.

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Fig. 3. Amplified NFATc1 induces its target genes to regulate osteoclast differentiation, cell fusion, and function. NFATc1 represses negative regulators such as MafB, IRF-8, and Bcl6 during osteoclast differentiation by inducing Blimp1 and Sirt6, which act as transcription repressors. In addition, NFATc1 cooperates with other transcription factors such as MITF, c-Fos, and PU.1 to regulate osteoclast fusion by inducing DC-STAMP, Atp6v0d2, and Tks5. The αVβ3 integrin signal activates c-Src by binding to vitronectin. Next, c-Src phosphorylates Syk, which recruits DAP12 and SLP-76 to form a complex with Vav3. This complex activates Rac1 or Cdc42 and regulates the cytoskeleton organization that is important for regulating bone resorption. MafB, v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B; IRF-8, interferon regulatory factor-8; Bcl6, B cell lymphoma 6; Blimp1, B-lymphocyte-induced maturation protein 1; Sirt6, sirtuin 6; MITF, microphthalmia-associated transcription factor; DC-STAMP, dendritic-cell-specific transmembrane protein; TRAP, tartrate-resistant acid phosphatase; Cdc42, cell division cycle 42.
Mol. Cells 2017;40:706~713
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