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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Vav1 inhibits RANKL-induced osteoclast differentiation and bone resorption

  • Jang, Jin Sun (Laboratory for Leukocyte Signaling Research, Department of Pharmacology, Inha University School of Medicine) ;
  • Kang, In Soon (Laboratory for Leukocyte Signaling Research, Department of Pharmacology, Inha University School of Medicine) ;
  • Cha, Young-Nam (Laboratory for Leukocyte Signaling Research, Department of Pharmacology, Inha University School of Medicine) ;
  • Lee, Zang Hee (Department of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University) ;
  • Dinauer, Mary C (Department of Pediatrics, Washington University School of Medicine) ;
  • Kim, Young-June (Department of Microbiology and Immunology, Indiana University School of Medicine) ;
  • Kim, Chaekyun (Laboratory for Leukocyte Signaling Research, Department of Pharmacology, Inha University School of Medicine)
  • Received : 2019.01.07
  • Accepted : 2019.04.24
  • Published : 2019.11.30
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Abstract

Vav1 is a Rho/Rac guanine nucleotide exchange factor primarily expressed in hematopoietic cells. In this study, we investigated the potential role of Vav1 in osteoclast (OC) differentiation by comparing the ability of bone marrow mononuclear cells (BMMCs) obtained from Vav1-deficient ($Vav1^{-/-}$) and wild-type (WT) mice to differentiate into mature OCs upon stimulation with macrophage colony stimulating factor and receptor activator of nuclear kappa B ligand in vitro. Our results suggested that Vav1 deficiency promoted the differentiation of BMMCs into OCs, as indicated by the increased expression of tartrate-resistant acid phosphatase, cathepsin K, and calcitonin receptor. Therefore, Vav1 may play a negative role in OC differentiation. This hypothesis was supported by the observation of more OCs in the femurs of $Vav1^{-/-}$ mice than in WT mice. Furthermore, the bone status of $Vav1^{-/-}$ mice was analyzed in situ and the femurs of $Vav1^{-/-}$ mice appeared abnormal, with poor bone density and fewer number of trabeculae. In addition, Vav1-deficient OCs showed stronger adhesion to vitronectin, an ${\alpha}_v{\beta}_3$ integrin ligand important in bone resorption. Thus, Vav1 may inhibit OC differentiation and protect against bone resorption.

Keywords

References

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