28.10.2013 Views

Understanding Hair Transplants and Hair Loss - Pacific Hair

Understanding Hair Transplants and Hair Loss - Pacific Hair

Understanding Hair Transplants and Hair Loss - Pacific Hair

SHOW MORE
SHOW LESS

You also want an ePaper? Increase the reach of your titles

YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.

oot sheath <strong>and</strong> in precursor cells of the hair shaft cortex <strong>and</strong> cuticle which lie immedi-<br />

ately adjacent to Wnt3-expressing cells.<br />

Millar found that overexpression of Dvl2 in the outer root sheath mimics the short-hair<br />

phenotype produced by overexpression of Wnt3 . This supports the hypothesis that<br />

Wnt3 <strong>and</strong> Dvl2 have the potential to act in the same pathway in the regulation of hair<br />

growth .<br />

These experiments demonstrate a previously unrecognized role for WNT signaling in<br />

the control of hair growth <strong>and</strong> structure, as well as presenting the first example of a<br />

mammalian phenotype resulting from overexpression of a Dvl gene <strong>and</strong> providing an<br />

accessible in vivo system for analysis of mammalian WNT signaling pathways .<br />

Bafico et al., (2001), report that Wnt signaling has an important role in hair follicle<br />

fate determination, tissue patterning <strong>and</strong> tumorigenesis . Secreted antagonists of Wnt<br />

include Frizzled (Fz)-related proteins (FRPs), Cerberus, Wnt inhibitory factor (WIF) <strong>and</strong><br />

Dickkopf (Dkk). FRPs, Cerberus <strong>and</strong> WIF have all been shown to act by binding <strong>and</strong><br />

sequestering Wnt . We report a novel mechanism of Wnt-signaling inhibition by human<br />

Dkk-1 . Dkk-1 demonstrated no interaction with Wnt but bound a single cell surface site<br />

with high affinity (KD=0.39 nM). Its receptor was detectable in a complex with a relative<br />

molecular mass of 240,000 (Mr 240K) with [125l] Dkk-1 by covalent affinity cross-linking<br />

. Wnt signaling through beta-catenin is mediated by the Fz receptor <strong>and</strong> a recently<br />

identified low-density-lipoprotein-receptor-related co-receptor, LRP6/Arrow. Overproduction<br />

of the 200K LRP6 protein, but not of Fz, strikingly increased Dkk-1 binding as<br />

well as the amount of the 240K cross-linked complex, which was shown to be composed<br />

of Dkk-1 <strong>and</strong> LRP6 . Moreover, Dkk-1 function was completely independent of Fz<br />

but LRP6 dramatically interfered with the Dkk-1 inhibition of Wnt signaling . Thus, unlike<br />

Wnt antagonists, which exert their effects by molecular mimicry of Fz or Wnt sequestration<br />

through other mechanisms, Dkk-1 specifically inhibits canonical Wnt signaling by<br />

binding to the LRP6 component of the receptor complex .<br />

S100A6 calcium binding protein is expressed in the epithelial sac of the hair follicle during<br />

regenerative processes (Ito <strong>and</strong> Kizawa, 2001). This protein is present in the bulge<br />

area where the stem cells are located during the catagen-telogen-anagen transition<br />

periods .<br />

Lu et al ., report that cytokeratin K19 is expressed in epithelial cells, basal cells of nonkeratinized<br />

stratified squamous epithelium, epidermal cells during the embryonic stage,<br />

<strong>and</strong> squamous carcinoma cells, but it is not expressed in adult epidermis. Interestingly,<br />

U n d e r s t a n d i n g H a i r T r a n s p l a n t s a n d H a i r L o s s<br />

38

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!