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Article

Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo

  • Authors:
    • Feng-Ning F. Yuan
    • Jayasanker Valiyaparambil
    • Michael C. Woods
    • Huy Tran
    • Rima Pant
    • John S. Adams
    • Sanjay M. Mallya
  • View Affiliations / Copyright

    Affiliations: Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, CA 90095, USA, University of Connecticut Health Center, School of Dental Medicine, Farmington, CT 06032, USA, Orthopaedic Hospital Research Center and Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA 90095, USA
  • Pages: 1625-1633
    |
    Published online on: March 12, 2014
       https://doi.org/10.3892/ijo.2014.2338
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Abstract

The secosteroidal hormone 1,25-dihyroxyvitamin D [1,25(OH)2D3] and its receptor, the vitamin D receptor (VDR), are crucial regulators of epidermal proliferation and differentiation. However, the effects of 1,25(OH)2D3-directed signaling on oral keratinocyte pathophysiology have not been well studied. We examined the role of 1,25(OH)2D3 in regulating proliferation and differentiation in cultured oral keratinocytes and on the oral epithelium in vivo. Using lentiviral-mediated shRNA to silence VDR, we generated an oral keratinocyte cell line with stable knockdown of VDR expression. VDR knockdown significantly enhanced proliferation and disrupted calcium- and 1,25(OH)2D3-induced oral keratinocyte differentiation, emphasizing the anti-proliferative and pro-differentiation effects of 1,25(OH)2D3 in oral keratinocytes. Using vitamin D3-deficient diets, we induced chronic vitamin D deficiency in mice as evidenced by decreased serum 25-hydroxyvitamin D (25OHD) concentrations. The vitamin D-deficient mice manifested increased proliferation of the tongue epithelium, but did not develop any morphological or histological abnormalities in the oral epithelium, suggesting that vitamin D deficiency alone is insufficient to alter oral epithelial homeostasis and provoke carcinogenesis. Immunohistochemical analyses of human and murine oral squamous cell carcinomas showed increased VDR expression. Overall, our results provide strong support for a crucial role for vitamin D signaling in oral keratinocyte pathophysiology.
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Copy and paste a formatted citation
Spandidos Publications style
Yuan FF, Valiyaparambil J, Woods MC, Tran H, Pant R, Adams JS and Mallya SM: Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo. Int J Oncol 44: 1625-1633, 2014.
APA
Yuan, F.F., Valiyaparambil, J., Woods, M.C., Tran, H., Pant, R., Adams, J.S., & Mallya, S.M. (2014). Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo. International Journal of Oncology, 44, 1625-1633. https://doi.org/10.3892/ijo.2014.2338
MLA
Yuan, F. F., Valiyaparambil, J., Woods, M. C., Tran, H., Pant, R., Adams, J. S., Mallya, S. M."Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo". International Journal of Oncology 44.5 (2014): 1625-1633.
Chicago
Yuan, F. F., Valiyaparambil, J., Woods, M. C., Tran, H., Pant, R., Adams, J. S., Mallya, S. M."Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo". International Journal of Oncology 44, no. 5 (2014): 1625-1633. https://doi.org/10.3892/ijo.2014.2338
Copy and paste a formatted citation
x
Spandidos Publications style
Yuan FF, Valiyaparambil J, Woods MC, Tran H, Pant R, Adams JS and Mallya SM: Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo. Int J Oncol 44: 1625-1633, 2014.
APA
Yuan, F.F., Valiyaparambil, J., Woods, M.C., Tran, H., Pant, R., Adams, J.S., & Mallya, S.M. (2014). Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo. International Journal of Oncology, 44, 1625-1633. https://doi.org/10.3892/ijo.2014.2338
MLA
Yuan, F. F., Valiyaparambil, J., Woods, M. C., Tran, H., Pant, R., Adams, J. S., Mallya, S. M."Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo". International Journal of Oncology 44.5 (2014): 1625-1633.
Chicago
Yuan, F. F., Valiyaparambil, J., Woods, M. C., Tran, H., Pant, R., Adams, J. S., Mallya, S. M."Vitamin D signaling regulates oral keratinocyte proliferation in vitro and in vivo". International Journal of Oncology 44, no. 5 (2014): 1625-1633. https://doi.org/10.3892/ijo.2014.2338
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