Vitamin B12 Activates the Wnt-Pathway in Human Hair Follicle Cells by Induction of beta-Catenin and Inhibition of Glycogensynthase Kinase-3 Transcription

Vitamin B12 Activates the Wnt-Pathway in Human Hair Follicle Cells by Induction of beta-Catenin and Inhibition of Glycogensynthase Kinase-3 Transcription

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.

Topical administration of cyanocobalamin (vitamin B12) showed suppression of potassium channel inhibitor (tolbutamide) and induction of murine hair anagen phase & synergistic effect with minoxidil.

Vitamin B12 is well known to be important for growth, cell reproduction, blood formation, and protein & tissue synthesis. Cyanocobalamin and hydroxocobalamin acetate are used to treat pernicious anemia, nutritional vitamin B12 deficiency, malabsorption of vitamin B12, and other cases of vitamin B12 deficiency.
We investigated the active effect of vitaminB12 on NIH3T3 fibroblast in ATP-sensitive potassium channel-dependent fashion and on murine anagen indution. The in vitro effects of established potassium channel openers (minoxidil) and inhibitors (tolbutamide), plus vitamin B12 were indirectly assessed on NIH3T3 fibroblast in the absence of aminoglycoside antibiotics & phenol red, and 5% fetal bovine serum-supplemented medium. Tolbutamide inhibited 28% proliferation of NH3T3 fibroblast at 2.5mM concentration as reported previously. When minoxidil & cyanocobalamin was treated to the fibroblast with 2.5mM tolbutamide, growth inhibition of NIH3T3 fibroblast was suppressed 51.49% by 100uM minoxidil 38.39% by 1uM cyanocobalamin, respectively. Two topical preparations of single dose of minoxidil (1%) and cyanocobalamin (0.03%) were topically administered with vehicle (ethanol/ propylene glycol/ water= 3/ 2/ 5) on clipped dorsal area of female telogen phase C57bl/6. The grown hair weights of topical 1% minoxidil preparation (113.14¡¾11.02mg, P<0.001) and 0.03% cyanocobalamin (59.56¡¾13.88mg, P<0.05) increased significantly than that of vehicle (18.47¡¾4.68mg). When topically administered in mixed preparations (0.5% minoxidil and 0.03% cyanocobalamin), the more grown hair weight (87.00¡¾8.39mg, P<0.03 t-test with 0.05% minoxidil) by mixed preparation was observed compared to those of single 0.5% minoxidil preparation (44.33¡¾14.96mg) & of vehicle preparation (22.13¡¾13.86mg). Topical cyanocobalamin was applied to atopic dermatitis and psoriasis in previous study; our new topical trial of vitamin B12 will be helpful treatment for alopecia as a single dose or coadministraition with minoxidil though the precise mechanism was not elucidated.