Pax6 expressed in osteocytes inhibits canonical Wnt signaling

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• 作者：Ajita Jami (12310)
  Jogeswar Gadi (12310)
  Min Jung Lee (22310)
  Eun Jin Kim (32310)
  Mi Jeong Lee (12310)
  Han-Sung Jung (22310)
  Hong-Hee Kim (42310)
  Sung-Kil Lim (12310) (32310)
  
• 关键词：canonical Wnt/尾 ; catenin signaling ; osteocytes ; Pax6 ; Sost ; Wnt3a
• 刊名：Molecules and Cells
• 出版年：2013
• 出版时间：April 2013
• 年：2013
• 卷：35
• 期：4
• 页码：305-312
• 全文大小：869KB
• 参考文献：1. Bai, S.W., Li, B., Zhang, H., Jonas, J.B., Zhao, B.W., Shen, L., and Wang, Y.C. (2011). Pax6 regulates proliferation and apoptosis of human retinoblastoma cells. Invest. Ophthalmol. Vis. Sci. / 52, 4560鈥?570. CrossRef
  2. Barrett, T., Troup, D.B., Wilhite, S.E., Ledoux, P., Rudnev, D., Evangelista, C., Kim, I.F., Soboleva, A., Tomashevsky, M., and Edgar, R. (2007). NCBI GEO: mining tens of millions of expression profiles database and tools update. Nucleic Acids Res. / 35, D760鈥揇765. CrossRef
  3. Berger, J., Berger, S., Tuoc, T.C., D鈥橝melio, M., Cecconi, F., Gorski, J.A., Jones, K.R., Gruss, P., and Stoykova, A. (2007). Conditional activation of Pax6 in the developing cortex of transgenic mice causes progenitor apoptosis. Development / 134, 1311鈥?322. CrossRef
  4. Carriere, C., Plaza, S., Caboche, J., Dozier, C., Bailly, M., Martin, P., and Saule, S. (1995). Nuclear localization signals, DNA binding, and transactivation properties of quail Pax6 (Pax-QNR) isoforms. Cell Growth Differ. / 6, 1531鈥?540.
  5. Cillo, C., Faiella, A., Cantile, M., and Boncinelli, E. (1999). Homeobox genes and cancer. Exp. Cell Res. / 248, 1鈥?. CrossRef
  6. Dallas, S.L., and Bonewald, L.F. (2010). Dynamics of the transition from osteoblast to osteocyte. Ann. N. Y. Acad. Sci. / 1192, 437鈥?43. CrossRef
  7. Franz-Odendaal, T.A., Hall, B.K., and Witten, P.E. (2006). Buried alive: How osteoblasts become osteocytes. Dev. Dyn. / 235, 176鈥?90. CrossRef
  8. Gotz, M., Stoykova, A., and Gruss, P. (1998). Pax6 controls radial glia differentiation in the cerebral cortex. Neuron / 21, 1031鈥?044. CrossRef
  9. Gunhaga, L., Marklund, M., Sjodal, M., Hsieh, J.C., Jessell, T.M., and Edlund, T. (2003). Specification of dorsal telencephalic character by sequential Wnt and FGF signaling. Nat. Neurosci. / 6, 701鈥?07. CrossRef
  10. Haubst, N., Berger, J., Radjendirane, V., Graw, J., Favor, J., Saunders, G.F., Stoykova, A., and Gotz, M. (2004). Molecular dissection of Pax6 function: the specific roles of the paired domain and homeodomain in brain development. Development / 131, 6131鈥?140. CrossRef
  11. Hodgson, S.V., and Saunders, K.E. (1980). A probable case of homozygous condition of the aniridia gene. J. Med. Genet. / 17, 478鈥?80. CrossRef
  12. Hogan, B.L., Hirst, E.M., Horsburgh, G., and Hetherington, C.M. (1988). Small eye (Sey): a mouse model for the genetic analysis of craniofacial abnormalities. Development / 103, 115鈥?19.
  13. Hsieh, Y.W., and Yang, X.J. (2009). Dynamic Pax6 expression during the neurogenic cell cycle influences proliferation and cell fate choices of retinal progenitors. Neural Dev. / 4, 32 CrossRef
  14. Jaworski, C., Sperbeck, S., Graham, C., and Wistow, G. (1997). Alternative splicing of Pax6 in bovine eye and evolutionary conservation of intron sequences. Biochem. Biophys. Res. Commun. / 240, 196鈥?02. CrossRef
  15. Johnson, M.L., Harnish, K., Nusse, R., and Van Hul, W. (2004). LRP5 and Wnt signaling: a union made for bone. J. Bone Miner. Res. / 19, 1749鈥?757. CrossRef
  16. Kato, Y., Windle, J.J., Koop, B.A., Mundy, G.R., and Bonewald, L.F. (1997). Establishment of an osteocyte -like cell line, MLOY4. J. Bone Miner. Res. / 12, 2014鈥?023. CrossRef
  17. Kaufman, M.H., Chang, H.H., and Shaw, J.P. (1995). Craniofacial abnormalities in homozygous Small eye (Sey/Sey) embryos and newborn mice. J. Anat. / 186, 607鈥?17.
  18. Kim, J., and Lauderdale, J.D. (2006). Analysis of Pax6 expression using a BAC transgene reveals the presence of a paired-less isoform of Pax6 in the eye and olfactory bulb. Dev. Biol. / 292, 486鈥?05. CrossRef
  19. Knothe Tate, M.L., Adamson, J.R., Tami, A.E., and Bauer, T.W. (2004). The osteocyte. Int. J. Biochem. Cell Biol. / 36, 1鈥?. CrossRef
  20. Krishnan, V., Bryant, H.U., and Macdougald, O.A. (2006). Regulation of bone mass by Wnt signaling. J. Clin. Invest. / 116, 1202鈥?209. CrossRef
  21. Lanyon, L.E. (1993). Osteocytes, strain detection, bone modeling and remodeling. Calcif. Tissue Int. / 53, 102鈥?07. CrossRef
  22. Lauderdale, J.D., Wilensky, J.S., Oliver, E.R., Walton, D.S., and Glaser, T. (2000). 3鈥?deletions cause aniridia by preventing Pax6 gene expression. Proc. Natl. Acad. Sci. USA / 97, 13755鈥?3759. CrossRef
  23. Li, X., Zhang, Y., Kang, H., Liu, W., Liu, P., Zhang, J., Harris, S.E., and Wu, D. (2005). Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J. Biol. Chem. / 280, 19883鈥?9887. CrossRef
  24. Ma, Y., Wu, X., Li, X., Fu, J., Shen, J., Li, X., and Wang, H. (2012). Corticosterone regulates the expression of neuropeptide Y and reelin in MLOY4 cells. Mol. Cells / 33, 611鈥?16. CrossRef
  25. Machon, O., Kreslova, J., Ruzickova, J., Vacik, T., Klimova, L., Fujimura, N., Lachova, J., and Kozmik, Z. (2010). Lens morphogenesis is dependent on Pax6 mediated inhibition of the Canonical Wnt/beta-Catenin signaling in the lens surface ectoderm. Genesis / 48, 86鈥?5.
  26. Manolagas, S.C. (2000). Birth and death of bone cells: basic regulatory mechanisms for the pathogenesis and treatment of osteoporosis. Endocr. Rev. / 21, 115鈥?37. CrossRef
  27. Park, S.J., Kim, S.J., Rhee, Y., Byun, J.H., Kim, S.H., Kim, M.H., Lee, E.J., and Lim, S.K. (2007). Fidgetin-like1 gene inhibited by basic fibroblast growth factor regulates the proliferation and differentiation of osteoblasts. J. Bone Miner. Res. / 22, 889鈥?96. CrossRef
  28. Poole, K.E., van Bezooijen, R.L., Loveridge, N., Hamersma, H., Papapoulos, S.E., Lowik, C.W., and Reeve, J. (2005). Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J. / 19, 1842鈥?844.
  29. Semenov, M., Tamai, K., and He, X. (2005). SOST is a ligand for LRP5/LRP6 and a WNT signaling inhibitor. J. Biol. Chem. / 280, 26770鈥?6775. CrossRef
  30. Shaham, O., Smith, A.N., Robinson, M.L., Taketo, M.M., Lang, R.A., and Ashery-Padan, R. (2009). Pax6 is essential for lens fiber cell differentiation. Development / 136, 2567鈥?578. CrossRef
  31. Stoykova, A., Fritsch, R., Walther, C., and Gruss, P. (1996). Forebrain patterning defects in small eye mutant mice. Development / 122, 3453鈥?465.
  32. Tang, H.K., Singh, S., and Saunders, G.F. (1998). Dissection of the transactivation function of the transcription factor encoded by the eye developmental gene Pax6. J. Biol. Chem. / 273, 7210鈥?221. CrossRef
  33. Theiler, K., Varnum, D.S., and Stevens, L.C. (1978). Development of Dickie鈥檚 small eye, a mutation in the house mouse. Anat. Embryol. (Berl) / 155, 81鈥?6. CrossRef
  34. van Bezooijen, R.L., Roelen, B.A., Visser, A., van der Wee-Pals, L., de Wilt, E., Karperien, M., Hamersma, H., Papapoulos, S.E., ten Dijke, P., and Lowik, C.W. (2004). Sclerostin is an osteocyte expressed negative regulator of bone formation, but not a classical BMP antagonist. J. Exp. Med. / 199, 805鈥?14. CrossRef
  35. van Bezooijen, R.L., Bronckers, A.L., Gortzak, R.A., Hogendoorn, P.C., van der Wee-Pals, L., Balemans, W., Oostenbroek, H.J., Van Hul, W., Hamersma, H., Dikkers, F.G., et al. (2009). Sclerostin in mineralized matrices and van buchem disease. J. Dent. Res. / 88, 569鈥?74. CrossRef
  36. Walther, C., and Gruss, P. (1991). Pax6, a murine paired box gene, is expressed in the developing CNS. Development / 113, 1435鈥?449.
  37. Weidauer, S.E., Schmieder, P., Beerbaum, M., Schmitz, W., Oschkinat, H., and Mueller, T.D. (2009). NMR structure of the Wnt modulator protein sclerostin. Biochem. Biophys. Res. Commun. / 380, 160鈥?65. CrossRef
  38. Wodarz, A., and Nusse, R. (1998). Mechanisms of Wnt signaling in development. Annu. Rev. Cell Dev. Biol. / 14, 59鈥?8. CrossRef
  39. Zhang, W., Cveklova, K., Oppermann, B., Kantorow, M., and Cvekl, A. (2001). Quantitation of Pax6 and Pax6(5a) transcript levels in adult human lens, cornea, and monkey retina. Mol. Vis. / 7, 1鈥?.
  
• 作者单位：Ajita Jami (12310)
  Jogeswar Gadi (12310)
  Min Jung Lee (22310)
  Eun Jin Kim (32310)
  Mi Jeong Lee (12310)
  Han-Sung Jung (22310)
  Hong-Hee Kim (42310)
  Sung-Kil Lim (12310) (32310)
  
  12310. Division of Endocrinology, Department of Internal Medicine, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 120-752, Korea
  22310. Division of Anatomy and Developmental Biology, Department of Oral Biology, Brain Korea 21 Project, Oral Science Research Center, College of Dentistry, Yonsei Center of Biotechnology, Yonsei University, Seoul, 120-752, Korea
  32310. Institute of Bio-Medical Sciences, Yonsei University, Seoul, 120-752, Korea
  42310. Department of Cell and Developmental Biology, Brain Korea 21 Program and Dental Research Institute, Seoul National University, Seoul, 110-749, Korea
  
• ISSN：0219-1032

文摘

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.