Pax6 expressed in osteocytes inhibits canonical Wnt signaling

• Published in: Molecules and cells Vol. 35; no. 4; pp. 305 - 312
• Main Authors: Jami, A., Yonsei University College of Medicine, Seoul, Republic of korea, Gadi, J., Yonsei University College of Medicine, Seoul, Republic of korea, Lee, M.J., Yonsei University, Seoul, Republic of korea, Kim, E.J., Yonsei University, Seoul, Republic of korea, Lee, M.J., Yonsei University College of Medicine, Seoul, Republic of korea, Jung, H.S., Yonsei University, Seoul, Republic of korea, Kim, H.H., Seoul National University, Seoul, Republic of korea, Lim, S.K., Yonsei University College of Medicine, Seoul, Republic of korea
• Format: Journal Article
• Language: English
• Published: Springer Korean Society for Molecular and Cellular Biology 01.04.2013; Korea Society for Molecular and Cellular Biology; 한국분자세포생물학회
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; canonical Wnt/beta-catenin signaling, osteocytes, Pax6, Sost, Wnt3a; Cell Biology; 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; Life Sciences; Mice; Osteocytes - cytology; Osteocytes - metabolism; Paired Box Transcription Factors - biosynthesis; Paired Box Transcription Factors - genetics; Paired Box Transcription Factors - metabolism; PAX6 Transcription Factor; Repressor Proteins - biosynthesis; Repressor Proteins - genetics; Repressor Proteins - metabolism; Research Article; TRANSCRIPCION; TRANSCRIPTION; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt Signaling Pathway - physiology; 생물학; Pax6; Sost; osteocytes; canonical Wnt/β-catenin signaling; Wnt3a
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-013-2310-0

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.