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T-oligos as differential modulators of human scalp hair growth and pigmentation: a new “time lapse system” for studying human skin and hair follicle biology in vitro?

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Abstract

Small DNA oligonucleotides homologous to the 3′ overhang of human telomeres, called T-oligos, stimulate pigmentation in human epidermal melanocytes in vitro and in vivo. They induce UV-mimetic effects in the absence of DNA-damage, however, it is unknown how T-oligos affect human hair follicle keratinocyte and melanocyte functions in situ. Here, we present the first evidence that these oligonucleotides are powerful modulators of pigmentation and growth of microdissected, organ-cultured human scalp hair follicles. Hair follicles were incubated with T-oligo or vehicle control and were then assessed for changes in hair shaft length, follicle morphology, pigmentation, proliferation and apoptosis. After only 48 h, T-oligos induced a fourfold increase in pigmentation of human anagen VI hair bulbs, while hair matrix keratinocyte proliferation was reduced by 65%, without apparent changes in hair bulb cell apoptosis. This corresponded well with a significant inhibition of hair shaft elongation, which was not accompanied by premature catagen induction in anagen VI hair follicles. These diametrically opposed effects of T-oligos on human hair follicle melanocytes (stimulation of melanogenesis) versus human hair bulb keratinocytes (inhibition of proliferation) in situ illustrate that human hair follicle organ culture offers an excellent tool for T-oligo research. They suggest that T-oligos deserve to be further explored for the management of clinical hair growth and pigmentation disorders, and raise the possibility that this model may offer a unique “time lapse system” for studying skin and hair follicle biology and DNA repair strategies under physiologically relevant conditions.

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References

  1. Hadshiew IM, Eller MS, Gasparro FP, Gilchrest BA (2001) Stimulation of melanogenesis by DNA oligonucleotides: effect of size, sequence and 5′ phosphorylation. J Dermatol Sci 25:127–138

    Article  PubMed  CAS  Google Scholar 

  2. Hadshiew IM, Eller MS, Gilchrest BA (2000) Stimulation of melanogenesis by oligonucleotides in vitro and in vivo. Arch Dermatol Res 292:117

    Google Scholar 

  3. Eller MS, Puri N, Hadshiew IM, Venna SS, Gilchrest BA (2002) Induction of apoptosis by telomere 3′ overhang-specific DNA. Exp Cell Res 276:185–193

    Article  PubMed  CAS  Google Scholar 

  4. Marwaha V, Chen YH, Helms E, Arad S, Inoue H, Bord E, Kishore R, Sarkissian RD, Gilchrest BA, Goukassian DA (2005) T-oligo treatment decreases constitutive and UVB-induced COX-2 levels through p53- and NFkappaB-dependent repression of the COX-2 promoter. J Biol Chem 16:32379–32388

    Article  Google Scholar 

  5. Eller MS, Maeda T, Magnoni C, Atwal D, Gilchrest BA (1997) Enhancement of DNA repair in human skin cells by thymidine dinucleotides: evidence for a p53-mediated mammalian SOS response. Proc Natl Acad Sci USA 94:12627–12632

    Article  PubMed  CAS  Google Scholar 

  6. Hadshiew IM, Khlgatian MK, Giese H, Eller MS, Vijg J, Gilchrest BA (1999) Reduktion der UV-induzierten Mutationstrate durch Behandlung mit dem Thymidin Dinucleotid (pTpT) (Reduction of UV-induced mutation frequency by treatment with thymidine dinucleotide, pTpT). In: Meigel (ed). Dermatologie an der Schwelle zum neuen Jahrtausend- Aktueller Stand von Klinik und Forschung. Springer, Berlin, pp 652–654

    Google Scholar 

  7. Hadshiew I, Barre K, Bódó E, Paus R (2005) T-oligos stimulate human scalp hair follicle pigmentation, but inhibit human hair matrix keratinocyte proliferation and hair shaft elongation. J Invest Dermatol Suppl abstr 789

  8. Ito T, Ito N, Saathoff M, Bettermann A, Takigawa M, Paus R (2005) Interferon-γ is a potent inducer of catagen-like changes in cultured human anagen hair follicle. Br J Dermatol 152:623–631

    Article  PubMed  CAS  Google Scholar 

  9. Paus R, Cotsarelis G (1999) The biology of hair follicles. N Engl J Med 341(7):491–497

    Article  PubMed  CAS  Google Scholar 

  10. Peters EM, Stieglitz MG, Liezman C, Overall RW, Nakamura M, Hagen E, Klapp BF, Arck P, Paus R (2006) p75 neurotrophin receptor-mediated signaling promotes human hair follicle regression (Catagen). Am J Pathol 168(1):221–234

    Article  PubMed  CAS  Google Scholar 

  11. Philpott M (1999) In vitro maintenance of isolated hair follicles: current status and future development. Exp Dermatol 8:317–319

    PubMed  CAS  Google Scholar 

  12. Botchkareva NV, Khlgatian M, Longley BJ, Botchkarev VA, Gilchrest BA (2001) Scf/c-Kit signaling is required for cyclic regeneration of the hair pigmentation unit. FASEB J 15:645–658

    Article  PubMed  CAS  Google Scholar 

  13. Slominski A, Wortsman J, Plonka PM et al (2005) Hair follicle pigmentation. J Invest Dermatol 124:13–21

    Article  PubMed  CAS  Google Scholar 

  14. Slominski A, Paus R, Plonka P et al (1994) Melanogenesis during the anagen-catagen-telogen transformation of the murine hair cycle. J Invest Dermatol 102:862–869

    Article  PubMed  CAS  Google Scholar 

  15. Slominski A, Paus R (1993) Melanogenesis is coupled to murine anagen: toward new concepts for the role of melanocytes and the regulation of melanogenesis in hair growth. J Invest Dermatol 101(1):90–97

    Article  Google Scholar 

  16. Tobin DJ, Slominski A, Botchkarev V, Paus R (1999) The fate of hair follicle melanocytes during the hair growth cycle. J Invest Dermatol Symp Proc 4:323–332

    Article  CAS  Google Scholar 

  17. Nishimura EK, Granter SR, Fisher DE (2005) Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science 307(5710):720–724

    Article  PubMed  CAS  Google Scholar 

  18. Tobin DJ, Paus R (2001) Graying: gerontobiology of the hair follicle pigmentary unit. Exp Gerontol 36:29–54

    Article  PubMed  CAS  Google Scholar 

  19. Bodó E, Tobin DJ, Kamenisch Y, Bíró T, Berneburg M, Funk W, Paus R (2007) Dissecting the impact of chemotherapy on the human hair follicle: a pragmatic in vitro assay for studying the pathogenesis and potential management of hair follicle dystrophy. Am J Pathol 171:1153–1167

    Article  PubMed  Google Scholar 

  20. Nylander K, Bourdon JC, Bray SE, Gibbs NK, Kay R, Hart I, Hall PA (2000) Transcriptional activation of tyrosinase and TRP-1 by p53 links UV irradiation to the protective tanning response. J Pathol 190(1):39–46

    Article  PubMed  CAS  Google Scholar 

  21. Atoyan RY, Sharov AA, Eller MS, Sargsyan A, Botchkarev VA, Gilchrest BA (2007) Oligonucleotide treatment increases eumelanogenesis, hair pigmentation and melanocortin-1 receptor expression in the hair follicle. Exp Dermatol 16(8):671–677

    Article  PubMed  CAS  Google Scholar 

  22. Gilchrest BA, Eller MS (1999) DNA photodamage stimulates melanogenesis and other photoprotective responses. J Investig Dermatol Symp Proc 4:35–40

    Article  PubMed  CAS  Google Scholar 

  23. Eller MS, Ostrom K, Gilchrest BA (1996) DNA damage enhances melanogenesis. Proc Natl Acad Sci USA 93:1087–1092

    Article  PubMed  CAS  Google Scholar 

  24. Eller MS, Yaar M, Gilchrest BA (1994) DNA damage and melanogenesis. Nature 372:413–414

    Article  PubMed  CAS  Google Scholar 

  25. Gilchrest BA, Park HY, Eller MS, Yaar M (1996) Mechanisms of ultraviolet light-induced pigmentation. Photochem Photobiol 63:1–10

    Article  PubMed  CAS  Google Scholar 

  26. Khlgatian MK, Hadshiew IM, Asawanonda P, Yaar M, Eller MS, Fujita M, Norris DA, Gilchrest BA (2002) Tyrosinase gene expression is regulated by p53. J Invest Dermatol 118(1):126–132

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, University Hospital Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Ina Hadshiew & Kirsten Barre

  2. Department of Dermatology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany

    Enikö Bódó & Ralf Paus

  3. Dr. Kozlowski Clinic, Munich, Germany

    Wolfgang Funk

Authors
  1. Ina Hadshiew
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  2. Kirsten Barre
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  3. Enikö Bódó
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  4. Wolfgang Funk
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  5. Ralf Paus
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Correspondence to Ina Hadshiew.

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Hadshiew, I., Barre, K., Bódó, E. et al. T-oligos as differential modulators of human scalp hair growth and pigmentation: a new “time lapse system” for studying human skin and hair follicle biology in vitro?. Arch Dermatol Res 300, 155–159 (2008). https://doi.org/10.1007/s00403-008-0833-6

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  • DOI: https://doi.org/10.1007/s00403-008-0833-6

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