Vitamin B12 Activates the Wnt-Pathway in Human Hair Follicle Cells by Induction of beta-Catenin and Inhibition of Glycogensynthase Kinase-3 Transcription
Walter Krugluger, Karl Stiefsohn, Katharina Laciak, Karl Moser, Claudia Moser
DOI: 10.4236/jcdsa.2011.12004   PDF   HTML     7,573 Downloads   16,272 Views   Citations


Background and Objectives: Micrograft transplantation is accompanied by a transient induction of telogen in transplanted hair follicles (HF), which might be avoided by supporting the metabolic pathways of the micrograft during the ex vivo period. Vitamin B12 (cobalamin) has been suggested to influence HF growth and cycling in humans, but the mechanisms are unclear. Method: HFs were obtained from patients undergoing routine micrograft transplantation and were cultured for 5 days in Dulbecco’s modified Eagles Medium, supplemented with different amounts of vitamin B12. Hair shaft elongation (HSE) of the isolated HFs as well as quantitative changes of mRNA for beta-catenin, glykogensynthase kinase-3 (GSK-3) and TCF/Lef-1 in HF cells were determined. Results: In vitro HSE demonstrated a dose dependent induction of HSE after stimulation with 2.5 ug/ml and 25 ug/ml vitamin B12 (6.2 +/- 2.1% and 15.4 +/- 3.8% respectively). A dose dependent induction of beta-catenin-mRNA could be demonstrated in cultured HFs after stimulation with 2.5 ug/ml and 25 ug/ml vitamin B12 (fold change compared to DMEM: 9.5 +/- 2.7, p < 0.05 and 23.1 +/- 7.4, p < 0.01; respectively). Concomitantly the amounts of GSK-3 were significantly reduced after stimulation with 25 ug/ml vitamin B12 (fold change compared to DMEM: 0.76 +/- 0.12, p < 0.05). Conclusions: Our data demonstrate a hair growth promoting effect of vitamin B12 in vitro. This effect is accompanied by the modulation of intracellular signal transduction molecules of the wnt-pathway and might promote hair growth after micrograft transplantation.

Share and Cite:

W. Krugluger, K. Stiefsohn, K. Laciak, K. Moser and C. Moser, "Vitamin B12 Activates the Wnt-Pathway in Human Hair Follicle Cells by Induction of beta-Catenin and Inhibition of Glycogensynthase Kinase-3 Transcription," Journal of Cosmetics, Dermatological Sciences and Applications, Vol. 1 No. 2, 2011, pp. 25-29. doi: 10.4236/jcdsa.2011.12004.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] R. H. Allen, S. P. Stabler, D. G. Savage and J. Lindenbaum, “Metabolic Abnormalities in Cobalamin (Vitamin B12) and Folate Deficiency,” Journal of the Federation of American Societies for Experimental Biology, Vol. 7, No. 14, 1993, pp. 1344-1352.
[2] P. R. Walker, B. Smith, C. Carson, J. Le Blanc, M. Sikorska, C. S. Woodhouse and S. C. Morgan, “Induction of Apoptosis in Neoplastic Cells by Depletion of Vitamin B12,” Cell Death and Differentiation, Vol. 4, 1997, pp. 233-241. doi:10.1038/sj.cdd.4400225
[3] I. Volkov, Y. Press and I. Rudoy, “Vitamin B12 Could Be A ‘Master Key’ in the Regulation of Multiple Pathologic Processes,” Journal of Nippon Medical School, Vol. 73, No. 2, 2006, pp. 65-69. doi:10.1272/jnms.73.65
[4] E. Reynolds, “Vitamin B12, Folic Acid, and the Nervous System,” Lancet Neurology, Vol. 5, No. 11, 2006, pp. 949-960. doi:10.1016/S1474-4422(06)70598-1
[5] N. Srivastava, S. Chand, M. Bansal, K. Srivastava and S. Singh, “Reversible Hyperpigmentation as the First Manifestation of Dietary Vitamin B12 Deficiency,” Indian Journal of Dermatology Venereology and Leprology, Vol. 72, No. 5, 2006, pp. 389-930. doi:10.4103/0378-6323.27766
[6] R. Carmel, “Hair and Fingernail Changes in Acquired and Congenital Pernicious Anemia,” Archives of Internal Medicine, Vol. 145, 1985, pp. 484-485. doi:10.1001/archinte.145.3.484
[7] G. L. Wolff, R. L. Kodell, S. R. Moore and C. A. Cooney, “Maternal Epigenetics and Methyl Supplements Affect Agouti Gene Expression in Avy/A Mice,” Journal of the Federation of American Societies for Experimental Biology, Vol. 12, No. 11, 1998, pp. 949-957.
[8] N. H. Park, “Topical Administration of Cyanocobalamin (Vitamin B12) Showed Suppression of Potassium Channel Inhibitor (Tolbutamide) and Induction of Murine Hair Anagen Phase and Synergistic Effect with Minoxidil,” Dermatology, Vol. 213, No. 1, 2006, pp. 53-80.
[9] K. S. Stenn and R. Paus, “Controls of Hair Follicle Cycling,” Physiological Reviews, Vol. 8, No. 1, 2001, pp. 449-494.
[10] C. Fathke, L. Wilson, K. Shah, B. Kim, A. Hocking, R. Moon and F. Isik, “Wnt Signaling Induces Epithelial Differentiation during Cutaneous Wound Healing,” BMC Cell Biology, Vol. 7, 2006, p. 4. doi:10.1186/1471-2121-7-4
[11] S. Estrach, C. A. Ambler, C. Lo Celso, K. Hozumi and F. M. Watt, “Jagged 1 Is a ?-Catenin Target Gene Required for Ectopic Hair Follicle Formation in Adult Epidermis,” Development, Vol. 133, 2006, pp. 4427-4438. doi:10.1242/dev.02644
[12] D. Van Mater, F. T. Kolligs, A. A. Dlugosz and E. R. Fearson, “Transient Activation of Beta-Catenin Signaling in Cutaneous Keratinocytes Is Sufficient to Trigger the Active Growth Phase of the Hair Cycle in Mice,” Genes & Development, Vol. 17, No. 10, 2003, pp. 1219-1224. doi:10.1101/gad.1076103
[13] M. P. Philpott and T. Kealey, “Effects of EGF on the Morphology and Patterns of DNA Synthesis in Isolated Human Hair Follicles,” Journal of Investigative Dermatology, Vol. 102, 1994, pp. 186-191. doi:10.1111/1523-1747.ep12371760
[14] C. S. Harmon and T. D. Nevins, “Evidence that Activation of Protein Kinase a Inhibits Human Hair Follicle Growth and Hair Fibre Production in Organ Culture and DNA Synthesis in Human and Mouse Hair Follicle Organ Culture,” British Journal of Dermatology, Vol. 136, No. 6, 1997, pp. 853-858. doi:10.1111/j.1365-2133.1997.tb03924.x
[15] R. Hirota, S. Tajima, Y. Yoneda T. Tamayama, M. Watanabe, K. Ueda, T. Kubota and R. Yoshida, “Alopecia of IFN-Gamma Knockout Mouse as a Model for Disturbance of the Hair Cycle: A Unique Arrest of the Hair Cycle at the Anagen Phase Accompanied by Mitosis,” Journal of Interferon and Cytokine Research, Vol. 22, No. 9, 2002, pp. 935-945. doi:10.1089/10799900260286641
[16] C. M. Baker, A. Verstuyf, K. B. Jensen and F. M. Watt, “Differential Sensitivity of Epidermal Cell Subpopulations to Beta-Catenin-Induced Ectopic Hair Follicle Formation,” Developmental Biology, Vol. 343, 2010, pp. 40-50. doi:10.1016/j.ydbio.2010.04.005
[17] O. S. Kwon, J. K. Oh, M. H. Kim, S. H. Park, H. K. Pyo, K. H. Kim, K. H. Cho and H. C. Eun, “Human Hair Growth Ex Vivo is Correlated with in Vivo Hair Growth: Selective Categorization of Hair Follicles for More Reliable Hair Follicle Organ Culture,” Archives of Dermatological Research, Vol. 297, No. 8, 2006, pp. 367-371. doi:10.1007/s00403-005-0619-z
[18] B. Seetharam, “Receptor-Mediated Endocytosis of Cobalamin (Vitamin B12),” Annual Review of Nutrition, Vol. 19, No. 1, 1999, pp. 173-195. doi:10.1146/annurev.nutr.19.1.173
[19] C. A. Hall and P. D. Colligen, “The Function of Cellular Transcobalamin II in Cultured Human Cells,” Experimental Cell Research, Vol. 183, No. 1, 1989, pp. 159-167. doi:10.1016/0014-4827(89)90426-6

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.