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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Dikkopf-1 promotes matrix mineralization of osteoblasts by regulating Ca+-CAMK2A- CREB1 pathway

  • Hyosun, Park (Hanyang University Institute for Rheumatology Research) ;
  • Sungsin, Jo (Hanyang University Institute for Rheumatology Research) ;
  • Mi-Ae, Jang (Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine) ;
  • Sung Hoon, Choi (Department of Orthopedic Surgery, Hanyang University Seoul Hospital) ;
  • Tae-Hwan, Kim (Hanyang University Institute for Rheumatology Research)
  • Received : 2022.06.23
  • Accepted : 2022.10.07
  • Published : 2022.12.31
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Abstract

Dickkopf-1 (DKK1) is a secreted protein that acts as an antagonist of the canonical WNT/β-catenin pathway, which regulates osteoblast differentiation. However, the role of DKK1 on osteoblast differentiation has not yet been fully clarified. Here, we investigate the functional role of DKK1 on osteoblast differentiation. Primary osteoprogenitor cells were isolated from human spinal bone tissues. To examine the role of DKK1 in osteoblast differentiation, we manipulated the expression of DKK1, and the cells were differentiated into mature osteoblasts. DKK1 overexpression in osteoprogenitor cells promoted matrix mineralization of osteoblast differentiation but did not promote matrix maturation. DKK1 increased Ca+ influx and activation of the Ca+/calmodulin-dependent protein kinase II Alpha (CAMK2A)-cAMP response element-binding protein 1 (CREB1) and increased translocation of p-CREB1 into the nucleus. In contrast, stable DKK1 knockdown in human osteosarcoma cell line SaOS2 exhibited reduced nuclear translocation of p-CREB1 and matrix mineralization. Overall, we suggest that manipulating DKK1 regulates the matrix mineralization of osteoblasts by Ca+-CAMK2A-CREB1, and DKK1 is a crucial gene for bone mineralization of osteoblasts.

Keywords

Acknowledgement

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (2019 R1A2C2004214, 2020R1A2C1102386, and 2021R1A6A1A03038899).

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