Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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ST5 Positively Regulates Osteoclastogenesis via Src/Syk/Calcium Signaling Pathways

  • Kim, Min Kyung (Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute (DRI), School of Dentistry, Seoul National University) ;
  • Kim, Bongjun (Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute (DRI), School of Dentistry, Seoul National University) ;
  • Kwon, Jun-Oh (Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute (DRI), School of Dentistry, Seoul National University) ;
  • Song, Min-Kyoung (Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute (DRI), School of Dentistry, Seoul National University) ;
  • Jung, Suhan (Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute (DRI), School of Dentistry, Seoul National University) ;
  • Lee, Zang Hee (Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute (DRI), School of Dentistry, Seoul National University) ;
  • Kim, Hong-Hee (Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute (DRI), School of Dentistry, Seoul National University)
  • Received : 2019.08.23
  • Accepted : 2019.09.25
  • Published : 2019.11.30
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Abstract

For physiological or pathological understanding of bone disease caused by abnormal behavior of osteoclasts (OCs), functional studies of molecules that regulate the generation and action of OCs are required. In a microarray approach, we found the suppression of tumorigenicity 5 (ST5) gene is upregulated by receptor activator of nuclear $factor-{\kappa}B$ ligand (RANKL), the OC differentiation factor. Although the roles of ST5 in cancer and ${\beta}-cells$ have been reported, the function of ST5 in bone cells has not yet been investigated. Knockdown of ST5 by siRNA reduced OC differentiation from primary precursors. Moreover, ST5 downregulation decreased expression of NFATc1, a key transcription factor for osteoclastogenesis. In contrast, overexpression of ST5 resulted in the opposite phenotype of ST5 knockdown. In immunocytochemistry experiments, the ST5 protein is colocalized with Src in RANKL-committed cells. In addition, ST5 enhanced activation of Src and Syk, a Src substrate, in response to RANKL. ST5 reduction caused a decrease in RANKL-evoked calcium oscillation and inhibited translocation of NFATc1 into the nucleus. Taken together, these findings provide the first evidence of ST5 involvement in positive regulation of osteoclastogenesis via Src/Syk/calcium signaling.

Keywords

References

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