Dickkopf 1 promotes regression of hair follicles.

squeegee

Banned
Reaction score
129
J Invest Dermatol. 2012 Jun;132(6):1554-60. doi: 10.1038/jid.2012.24. Epub 2012 Feb 23.
Dickkopf 1 promotes regression of hair follicles.

Kwack MH, Kim MK, Kim JC, Sung YK.
Source

Department of Immunology, School of Medicine, Kyungpook National University, Daegu, Korea.

Abstract

Recently, we suggested that Dickkopf 1 (DKK-1) is a pathogenic mediator involved in male pattern baldness. As premature catagen onset is a key characteristic of male pattern baldness, in this study, we evaluated whether DKK-1 has a role as a catagen inducer in hair cycling. Herein, we report that recombinant human DKK-1 (rhDKK-1) injection into the hypodermis of mice during anagen caused premature onset of catagen, whereas neutralizing DKK-1 antibody delayed anagen-to-catagen transition in mice. Moreover, treatment with rhDKK-1 led to a decrease in final hair follicle length, whereas DKK-1 antibody led to an increase compared with control animals. In addition, DKK-1 and DKK-1 messenger RNA expression is most upregulated in follicular keratinocytes of late anagen in depilation-induced hair cycle progression. Moreover, we observed that rhDKK-1 blocks canonical Wnt-mediated activation of β-catenin signaling and induces the proapoptotic protein Bax, resulting in apoptosis in outer root sheath keratinocytes. Taken together, our data strongly suggest that DKK-1 is involved in anagen-to-catagen transition in the hair cycle by regulating the activity of follicular keratinocytes.

[h=2]Dihydrotestosterone-Inducible Dickkopf 1 from Balding Dermal Papilla Cells Causes Apoptosis in Follicular Keratinocytes[/h]
Recent studies suggest that androgen-driven alteration to the autocrine and paracrine factors produced by scalp dermal papilla (DP) cells may be a key to androgen-potentiated balding. Here, we screened dihydrotestosterone (DHT)-regulated genes in balding DP cells and found that dickkopf 1 (DKK-1) is one of the most upregulated genes. DKK-1 messenger RNA is upregulated in 3–6 hours after 50–100 nM DHT treatment and ELISA showed that DKK-1 is secreted from DP cells in response to DHT. A co-culture system using outer root sheath (ORS) keratinocytes and DP cells showed that DHT inhibits the growth of ORS cells, and neutralizing antibody against DKK-1 significantly reversed the growth inhibition of ORS cells. Analysis of co-cultured ORS cells showed a significant increment of sub-G1 apoptotic cells in response to DHT. Also, recombinant human DKK-1 inhibited the growth of ORS cells and triggered apoptotic cell death. In addition, DHT-induced epithelial cell death in cultured hair follicles was reversed by neutralizing DKK-1 antibody. Moreover, immunoblotting showed that the DKK-1 level is up in the bald scalp compared with the haired scalp of patients with androgenetic alopecia. Altogether, our data strongly suggest that DHT-inducible DKK-1 is involved in DHT-driven balding.

http://www.nature.com/jid/journal/v128/n2/full/5700999a.html
 

Sparky4444

Senior Member
Reaction score
44
....things ARE HAPPENING!....the pieces of the puzzle are coming together....male pattern baldness is a systematic process...many inputs and processes that need to work together...we're getting closer to turning off the tap!
 

waynakyo

Experienced Member
Reaction score
91
why didn't we hear about this before..
 

abcdefg

Senior Member
Reaction score
765
Yeah as we piece this together we get more places that we can try to intervene in the process. I still wonder though if all hair loss even minor supposedly age related thinning everyone gets is completely controlled by all of this like DHT being the trigger or if no androgens hair loss can still happen other ways.
 

squeegee

Banned
Reaction score
129
bump!
 

chicknlittle

Member
Reaction score
4
looks like there are problems with topical L-ascorbic acid 2-phosphate (it metabolizes during absorption to an inactive form not promoting hair growth)... Finding an effective way to deliver without degredation would take study

From article "since (metabolized L-ascorbic 2P) has no benifit for hair growth in the treatment of androgenic alopeci, A2p needs to penetrate skin (epidermal and dermal layers) without being metabolized to AA during the skin penetration process... Present study showed that significant amount of A2P was metabolized to (metabolite) during the penetration when the drug was applied ton the skin as of entrapped into MLV's, and the application of A2p as of PMX with empty MLVs reduced the metabolism of the drug. ... Further study is warrented. "

http://www.springerlink.com/content/v08502h52x1132l1/
 

Flynn

New Member
Reaction score
0
Reading the study in full yields this finding:
"Furthermore, the use of PMX of A2P with empty cationic
MLV demonstrated minimal or no metabolism of the
parent drug, indicating that A2P might be better benefited
with the use of PMX rather than entrapment into the
MLVs."
The conclusion of the study is that lipid entrapped formulations result in greater metabolism of Asc 2-P into Vitamin C. They have graphs showing comparisons of Asc-2P concentrations in skin based on the vehicles used.
 

chicknlittle

Member
Reaction score
4
What I get from the paper is that simply swallowing or applying L-ascorbic acid 2-phosphate is ineffective for hair growth due to liver or skin metabolism to vitamin C. Penetration of L-AA 2 Phosphate with PMX (physical mixture) of empty MLV (Multi Laminate Vesicles) seems to be most effective in getting drug where it needs to be. To me that means that while there might be benefit to taking a specially prepared preparation of l-AA 2 Phosphate (as a mixture of MLV) (more study needed re-benifit in people/hair growth?) I cannot simply swallow or rub L-ascorbic acid 2-phosphate on my scalp with means available to me and see benefit (as I dont know how to make a physical mixture of L-AA 2P with MLVs) Someone may figure out how to do the proper mixture/coating to allow adequate penetration, but that doesn't sound like a stable/home brew recipe to me.. Can't simply mix with alcohol/PPG.



 

Born4Hair

New Member
Reaction score
1
Theaflavine

Reduce the overexpression from DKK1 and reduce DHT better than finasteride.
Teaflavine are in Black Tea but not in Green Tea (Becuase Teaflavine are fermentent Catcheins)

Blacktea in the morning and after sport rise also down the Cholesterin level.

Recomend is 2-4 Cups black tee per day.
But not if you take a Zink supplement take it 30min before or after black tee.
 

squeegee

Banned
Reaction score
129
bump.
 

squeegee

Banned
Reaction score
129
bump.
 

prohair

New Member
Reaction score
1
Reduce the overexpression from DKK1 and reduce DHT better than finasteride.
Teaflavine are in Black Tea but not in Green Tea (Becuase Teaflavine are fermentent Catcheins)

Is there evidence that Theaflavine reduce expression of DKK1?

I did some searching and I don't see where this claim came from.

Thanks.
 

TheHandsomeLurker

Established Member
Reaction score
21
While this doesn't give us any functional treatments just yet, it's a further step towards curing male pattern baldness, and a pretty powerful one at that. If I recall, UPenn researchers have already showed that removing DKK1 restores dormant hair follicles.
 
K

karankaran

Guest
I found out that TNF-alpha is upstream of DKK1 and inhibition of TNF-alpha 'might' be effective too.

One more benefit - you will have good bone desnity if you do that.
 

TheHandsomeLurker

Established Member
Reaction score
21
I found out that TNF-alpha is upstream of DKK1 and inhibition of TNF-alpha 'might' be effective too.

One more benefit - you will have good bone desnity if you do that.

And from wikipedia:

Dysregulation of TNF production has been implicated in a variety of human diseases including Alzheimer's disease, cancer, major depression and inflammatory bowel disease (IBD).
 
Top