title: Pax6 expressed in osteocytes inhibits canonical Wnt signaling.
abstract: 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.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Ajita
authors.initials: A
authors.lastname: Jami
authors.forename: Jogeswar
authors.initials: J
authors.lastname: Gadi
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Kim
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Lee
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Jung
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
authors.forename: Sung-Kil
authors.initials: SK
authors.lastname: Lim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D051153:Wnt Proteins