Wnt signaling maintains the hair-inducing activity of the dermal papilla
The formation of the hair follicle and its cyclical growth, quiescence, and regeneration depend on reciprocal signaling between its epidermal and dermal components. The dermal organizing center, the dermal papilla (DP), regulates development of the epidermal follicle and is dependent on signals from the epidermis for its development and maintenance. GFP specifically expressed in DP cells of a transgenic mouse was used to purify this population and study the signals required to maintain it. We demonstrate that specific Wnts, but not Sonic hedgehog (Shh), maintain anagen-phase gene expression in vitro and hair inductive activity in a skin reconstitution assay.
http://genesdev.cshlp.org/content/14/10/1181.long
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Keratinocyte Growth Inhibition through the Modification of Wnt Signaling by Androgen in Balding Dermal Papilla Cells
- Author Affiliations
- Departments of Dermatology (T.K., H.T., N.K., S.K.) and Anatomy and Neurobiology (T.K., K.-I.M., M.K.), Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto 602-5586, Japan; and Department of Regenerative Dermatology (S.In., S.It.), Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
- Address all correspondence and requests for reprints to: Kawata, Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kawaramachi Hirokouji, Kamigyo-ku, Kyoto 602-8566, Japan. E-mail:
Abstract
Context/Objective: Androgen induces androgenetic alopecia (Androgenetic Alopecia), which has a regressive effect on hair growth from the frontal region of the scalp. Conversely, Wnt proteins are known to positively affect mammalian hair growth. We hypothesized that androgen reduces hair growth via an interaction with the Wnt signaling system. The objective of this study was to investigate the effect of androgen on Wnt signaling in dermal papilla (DP) cells.
Design: The effect of androgen and Wnt3a on keratinocyte proliferation was measured by use of a coculture system consisting of DP cells and keratinocytes. The molecular mechanisms of androgen and Wnt pathway interactions in DP cells were examined by analyzing the expression, intracellular localization, and activity of the androgen receptor (AR) and also downstream Wnt signaling molecules.
Results: Wnt3a-dependent keratinocyte growth was suppressed by the addition of dihydrotestosterone in coculture with DP cells that were derived from Androgenetic Alopecia patients, but growth was not suppressed in coculture with DP cells from non-Androgenetic Alopecia males. Whereas DP cells from both scalp regions expressed AR protein, the expression levels of AR and cotranslocation with β-catenin, a downstream Wnt signaling molecule, were higher in DP cells of Androgenetic Alopecia patients than in DP cells from non-Androgenetic Alopecia males.
In addition, significant suppression of Wnt signal-mediated transcription in response to dihydrotestosterone treatment was observed only in DP cells from Androgenetic Alopecia patients.
Conclusion: These results suggest that Wnt signaling in DP cells is regulated by androgen and this regulation plays a pivotal role in androgen’s action on hair growth.
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A decline in tissue regenerative capacity is a hallmark of mammalian aging and is, in part, attributed to the impairment of tissue stem/progenitor cell function. It was previously shown that the age-related decline in tissue-specific progenitor cell activity is modulated by factors that are present in the serum.[SUP]
58[/SUP] In line with this study, Brack et al[SUP]
52[/SUP] provided evidence showing that systemic factors in the serum of aged mice activate canonical Wnt signaling and contribute to age-related decline in skeletal muscle regeneration. The authors showed that skeletal muscle stem cells (satellite cells) convert from a myogenic to a fibrogenic lineage when exposed to aged serum and that canonical Wnt signaling is enhanced in skeletal muscle of aged mice and in cultured satellite cells exposed to aged serum. Moreover, skeletal muscle regeneration in young animals was attenuated by Wnt3A treatment, whereas impaired muscle regeneration in aged mice was restored by inhibition of canonical Wnt signaling. These observations suggest that activation of Wnt signaling by the “Wnt-like substance” present in the serum of aged organisms contributes to a decline in tissue stem cell function and impaired tissue regeneration associated with aging.
http://circres.ahajournals.org/content/107/11/1295.full
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Oxidative Stress Antagonizes Wnt Signaling in Osteoblast
Precursors by Diverting
-Catenin from T Cell Factor- to
Forkhead Box O-mediated Transcription
http://www.jbc.org/content/282/37/27298.full.pdf
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I much prefer the other one. For some reason I can't take seriously what you post with that old avatar.
Why so serious? Because Kermit the frog was better?
You will get over it Odal! LOL
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[h=1]The vitamin D receptor, the skin and stem cells.[/h]
Luderer HF,
Demay MB.
[h=3]Source[/h]Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, 50 Blossom St, Thier 11, Boston, MA 02114, USA.
[h=3]Abstract[/h]The active metabolite of vitamin D, 1,25-dihydroxyvitamin D, has been shown to have pro-differentiation and antiproliferative effects on keratinocytes that are mediated by interactions with its nuclear receptor. Other cutaneous actions of the vitamin D receptor have been brought to light by the cutaneous phenotype of humans and mice with non-functional vitamin D receptors. Although mice lacking functional vitamin D receptors develop a normal first coat of hair, they exhibit impaired cyclic regeneration of hair follicles that leads to the development of alopecia. Normal hair cycling involves reciprocal interactions between the dermal papilla and the epidermal keratinocyte. Studies in mice with targeted ablation of the vitamin D receptor demonstrate that the abnormality in the hair cycle is due to a defect in the keratinocyte component of the hair follicle. Furthermore, expression of mutant vitamin D receptor transgenes in the keratinocytes of vitamin D receptor knockout mice demonstrates that the effects of the receptor that maintain hair follicle homeostasis are ligand-independent. Absence of a functional vitamin D receptor leads to impaired function of keratinocyte stem cells, both in vivo and in vitro. This is manifested by impaired cyclic regeneration of the hair follicle, a decrease in bulge keratinocyte stem cells with ageing and an abnormality in lineage progression of these cells, leading to their preferential differentiation into sebocytes.
Copyright (c) 2010. Published by Elsevier Ltd.
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[h=1]Vitamin D receptor is essential for normal keratinocyte stem cell function[/h]
[h=2]Abstract[/h] The major physiological role of the vitamin D receptor (VDR) is the maintenance of mineral ion homeostasis. Mutation of the VDR, in humans and mice, results in alopecia. Unlike the effects of the VDR on mineral ion homeostasis, the actions of the VDR that prevent alopecia are ligand-independent. Although absence of the VDR does not prevent the development of a keratinocyte stem cell niche in the bulge region of the hair follicle, it results in an inability of these stem cells to regenerate the lower portion of the hair follicle
in vivo and impairs keratinocyte stem cell colony formation
in vitro. VDR ablation is associated with a gradual decrease in keratinocyte stem cells, accompanied by an increase in sebaceous activity, a phenotype analogous to that seen with impaired canonical Wnt signaling. Transient gene expression assays demonstrate that the cooperative transcriptional effects of β-catenin and Lef1 are abolished in keratinocytes isolated from VDR-null mice, revealing a role for the unliganded VDR in canonical Wnt signaling. Thus, absence of the VDR impairs canonical Wnt signaling in keratinocytes and leads to the development of alopecia due to a defect in keratinocyte stem cells.
http://www.pnas.org/content/104/22/9428.full
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You're not comparing it to Proctor's site..are you? :woot:
I don't know of anyone else that does custom products for individuals. Or even small batches. At least not liposomal-type topicals.
He's always ended up responding to my emails..eventually. But I feel your frustration..this is the longest it's been for me too
Is Elsom cGMP qualified? I am afraid that the FDA gonna shut it down..