Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 518, Issue 2, Pages 233-238Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.08.038
Keywords
FGF23; Notch; Bone; Osteocyte; Transgenic mouse
Categories
Funding
- MEXT
- Tokyo Dental College (Branding Project for Multidisciplinary Research Center for Jaw Disease: MRCJD)
Ask authors/readers for more resources
Fgf23 acts as a phosphaturic factor secreted from osteocytes in bone, but the mechanism regulating Fgf23 is not fully understood. Here, we showed the colocalization of Fgf23, Notch, and Hes1, a downstream target of Notch signaling, in numerous osteocytes in cortical bone of femur in wild-type mice. We generated NICD (Notch intracellular domain)-transgenic mice driven by a 2.3 kb collagena alpha 1 (I) (Col1a1) promoter fragment. Western blot and RT-PCR analyses revealed upregulation of Notch protein and mRNA levels in the bones of transgenic mice compared with those in wild-type mice. In the transgenic mice, immunohistochemical studies demonstrated that numerous osteocytes and osteoblasts express Notch in the rib, whereas only osteoblasts exhibit Notch in the femur. NICD-transgenic mice were characterized by upregulation of Fgf23 mRNA levels in the rib but not in the femur compared with that in wild type mice. These mice exhibited dwarfism associated with an osteomalacia phenotype. The expression of Alpl, Cal1a1, and Bglap decreased in NICD-transgenic mice compared with wild-type mice. UMR-106 cells cultured on Jagged1-immobilized wells significantly increased Fgf23 expressions associating with upregulation of Hes1 and Hey1. These results imply that Notch signaling is a positive regulator for Fgf23 expression in osteocytes. (C) 2019 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available