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- Title
The Shisa3 knockout mouse exhibits normal bone phenotype.
- Authors
Murakami, Kohei; Zhifeng, He; Suzuki, Takako; Kobayashi, Yasuhiro; Nakamura, Yukio
- Abstract
Wnt signaling is important for both skeletal development and bone disease, with Wnt inhibitory factors playing critical roles in bone metabolism. SHISA3 blocks the maturation and transportation of Frizzled receptors to the cell surface, thereby inhibiting the Wnt/β-catenin signaling pathway in lung cancer. However, the function of Shisa3 in bone biology remains uninvestigated. This study found that Shisa3 was strongly expressed in the calvarial bones of mice, especially in osteoblasts. In addition, adenovirus-mediated gene transfer of murine Shisa3 significantly inhibited Wnt3a-induced nuclear translocation of β-catenin and mRNA expression of the Wnt target gene Axin2. In bone phenotype assessments of Shisa3 knockout (Shisa3 KO) mice, micro-computed tomography, mRNA expressions of osteoblast markers, and skeletal preparations all displayed no significant differences compared with Shisa3 wild-type mice. mRNA expression analysis of canonical Wnt signaling target genes (Axin2, Lef1, Dkk1, and Tnfrsf11b) in calvarial bones at P0.5 also revealed no significant findings. In Axin2Cre/ERT2 knock-in mice, the number of Axin2-expressing cells in the calvariae of Shisa3 KO and control mice were comparable. Thus, there appears to be a redundancy in the function of Shisa3 in bone development, likely with other Shisa family members.
- Subjects
WNT signal transduction; OSTEOBLASTS; BONE diseases; BONE metabolism; CELL membranes
- Publication
Journal of Bone & Mineral Metabolism, 2019, Vol 37, Issue 6, p967
- ISSN
0914-8779
- Publication type
journal article
- DOI
10.1007/s00774-019-01014-y