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Pax6 Expressed in Osteocytes Inhibits Canonical Wnt Signaling

 Ajita Jami  ;  Jogeswar Gadi  ;  Min Jung Lee  ;  Eun Jin Kim  ;  Mi Jeong Lee  ;  Han-Sung Jung  ;  Hong-Hee Kim  ;  Sung-Kil Lim 
 MOLECULES AND CELLS, Vol.35(4) : 305-312, 2013 
Journal Title
Issue Date
Animals ; Cell Differentiation/physiology ; Cell Growth Processes/physiology ; Eye Proteins/biosynthesis* ; Eye Proteins/genetics ; Eye Proteins/metabolism ; Homeodomain Proteins/biosynthesis* ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; Immunohistochemistry ; Mice ; Osteocytes/cytology ; Osteocytes/metabolism* ; PAX6 Transcription Factor ; Paired Box Transcription Factors/biosynthesis* ; Paired Box Transcription Factors/genetics ; Paired Box Transcription Factors/metabolism ; Repressor Proteins/biosynthesis* ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Wnt Proteins/genetics ; Wnt Proteins/metabolism ; Wnt Signaling Pathway/physiology*
canonical Wnt/β-catenin signaling ; osteocytes ; Pax6 ; Sost ; Wnt3a
The transcription factor Pax6, which belongs to the paired box-containing gene family, regulates developmental processes, especially in the eyes, central nervous tissues and craniofacial structures. However, the role of Pax6 in bone has never been studied exclusively. Here we report that Pax6 is expressed at both the mRNA and protein level in the calvaria and long bones of adult mice as well as osteocyte-like MLOY4 cells and suppresses the canonical Wnt signaling pathway. Moreover, the expression levels of Pax6 were much higher in the calvaria than the long bones, and Pax6 was also expressed at E16 to E18 in both the calvaria and long bones. Knockdown of Pax6 in MLOY4 cells did not affect cell proliferation or survival; however, the expression of Sost, an osteocyte marker gene, was significantly decreased. In addition, the overexpression of Pax6 suppressed the canonical Wnt signaling pathway by enhancing the expression of Sost. Furthermore, we also demonstrated that Pax6 binds to the Sost promoter and that stimulation of Sost transcription by Pax6 was dependent on a specific Pax6-binding sequence within the promoter. In conclusion, the results of the present study suggest that Pax6 is expressed in bone and may play an important role in osteocyte differentiation by controlling canonical Wnt signaling.
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1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Gadi, Jogeswar(가디죠게스)
Kim, Eun Jin(김은진)
Ajita, Jami(아지타자미)
Lee, Mi Jeong(이미정)
Lee, Min Jung(이민정)
Lim, Sung Kil(임승길)
Jung, Han Sung(정한성) ORCID logo https://orcid.org/0000-0003-2795-531X
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