DKK2 and Hairless vs. Hairy Skin

Last week, researchers and scientists led by University of Pennsylvania’s Dr. Sarah Millar published a fascinating new open-access journal article titled:

“Regional Control of Hairless versus Hair-Bearing Skin by Dkk2.”

It seems like the researchers were trying to find an answer to an age old question: why don’t humans have hair on their palms and soles?

I always assumed that human beings and most other animals have no hair follicles and dermal papilla cells on their palms and feet/soles.

However, it seems like this is not true. You can get hairy palms and hairy feet based on just one slight genetic alteration (the removal of Dkk2). In fact, some animals such as rabbits and polar bears do have hairy feet/paws due to this very reason.

Dkk2: Remove it if you want Hairy Palms

Dickkopf-related protein 2 (Dkk2) is a protein that is encoded by the Dkk2 gene. This gene, when expressed in the palms and feet, works to inhibit Wnt/β-catenin signaling. This in turn results in totally hairless skin in those regions. The authors term Dkk2 as a Wnt inhibitor.

The Penn Medicine research team that led this latest research found that when they genetically removed Dkk2 expression from the plantar skin of mice, the animals began to sprout hair in this previously hairless area. This was due to the removal of Wnt signal inhibition.

Wnt/β-catenin signaling is crucial for hair growth in any area of the human body, and is the most researched subject area when it comes to the search for a hair loss cure. Not surprisingly, by now I must have written at least 50 posts on this blog in which I at least briefly mention Wnt/β-catenin or Wnt signaling.

Dkk2 Hairy Skin
Song et al., Regional Control of Hairless versus Hair-Bearing Skin by Dkk2, Cell Reports (2018), https://doi.org/
10.1016/j.celrep.2018.11.017

Dkk2 and Baldness

According to this article, Some studies have found correlations between baldness and DKK2 levels, but it is unclear whether this relationship is causal in nature.

According to Dr. Millar:

“We’re interested in taking a look at the precise nature in the difference in DKK2 in balding scalps versus normally-haired scalps,” Millar said. “We don’t know the answer yet.”

It is interesting that several companies over the years have worked on products that could both reduce body hair and increase head hair. The most famous of these is Follicum, although the company no longer seems to be working on a body hair reduction product.

54 thoughts on “DKK2 and Hairless vs. Hairy Skin”

  1. It’s the end of 2018 boys and girls and really just 1 1/2 years ago this was suppose to be the time of a better treatment and thus…we don’t. I would think on history of hair loss forums dated back to 2001 …when I myself was too young..but I am sure your searches took you to places claiming in 2-3 years. Research is just that…its research. Tbh it’s more a ademic based for so.eone who is attaining a Ph.d or has one and wants more publication. Academic research doesn’t exactly translate to practice in medicine. An example many nurse practitioners and M.Ds don’t practice medicine but write papers and teach. Why? One is because their wanting to be a professor especially at research universities( it opens up more chance for publications and looks good on resume ). The main reason is because they are to scared to practice or can’t handle it…so to utilize all the debt to get the degrees you have to do something. Plenty of r&d copmanies…but breakthroughs I believe needs to be put in practice…

  2. ” Millar said. “We don’t know the answer yet.”
    To understand this method has to be long-term years.
    I think I’m Dkk2 a natural inhibitor in my body either /
    ● Does not move to scalp; Baldness is the result of other hormones such as: dht. jak.pgd2
    ● Moves because of an unknown bug that prevents WNT paths.
    The question that scientists are looking for /
    What happens in WNT paths

  3. Lol good luck getting an apology if that’s what you really think you need. You could ask shiseido first but your response will probably be an automated message in Japanese. Histogram told hellouser they would be out late 2017.

    America realistically is follica samumed 2020 2021 cell based cloning 2025 unless I’m wrong I don’t see anything coming out in America before follica. Please tell me I’m wrong. Riken japan 20 looks like the only thing. Terskikh would be great if he wasn’t so fast behind

    1. John Doe, that article looks far more advanced than anything on Riken’s website, so it’s great to see! I truly hope Riken is legit. Riken’s claims make sense and are just phenomenal, so now it comes down to real world proof.

  4. I agree with egg head. Maybe histogen too if get it fast tracked but that is a stretch. I honestly lost hope on all these treatments. Too much disappointment and scam products are still in the market making money. Nothing has changed since 2001. All research and current treatment.

  5. @ Mjones and Egghead … dont lose hope! Please keep in mind that science and Technology has changed dramatic since then. In 2001 quite everybody with AIDS and Cancer died! That changed!
    Since then IT Technology power multiplied Level by ca. 1000 times (Supercomputer). In 2001 Stem Cells and follicles, KROX, FOXO, JAKs, Metabilism, Nervs influence, Alpha reductase, Wnt pathway, Senescence, Anti Aging, CRISPR … all unknown area. I am sorry but its just stupid to say Nothing changed. … We are now in Phase 2 and 3 clinical Trials with at least 15 novel Drugs. There are at least 50 Universities and Major companies or Startups working on that issue. Knowing that drug development from idea to pharmacy takes up to 15 years we will cure or at least maintenance Baldness by 2020-2022 and get several new drugs every year after 2022.

  6. I hate waiting too but 2018 wasn’t that bad of a year for hair loss research/treatments!

    Samumed is in Phase 3
    Follica is about to start Phase 3
    Riken
    Replicel-Feb 2019 announcement?
    Cassiopea has Winlevi getting approved soon which is a lower percentage soltution to their androgenic alopecia solution.
    And countless others I’m probably missing.

    2018 wasn’t so bad. Let’s breathe and be patient. I think we’re in the final stretch.

  7. You are right Michael I’m just exhausted bro. Been struggling with this crap since 2001. Just seeing disappointment after disappointment. You can’t blame me for being disappointed and skeptical of everything. Even my main main cots. Hope you guys are right but my gut tells me history is a repeating pattern for mpb treatments. Big promises and weak results. Hope I’m wrong this time around….

  8. Let me run something by all y’all. If there is a ‘cure’ in say 2025. Or at least a real treatment for maintenance and some re growth. Why don’t you get a hair transplant to carry you over until 2025? In my opinion a good hair transplant is a cure, no?

      1. Wheeler and Chris. Hair transplants are fine so long as they’re FUE only.
        Never ever get FUT strip scars. Covering these each day has all but ruined my life. It’s far better to shave your hair short and maybe get some realistic tasteful SMP and FUE to add texture. Strip scar ruins your ability to clip your hair short, which is horrible if your hair looks thin and weak on top (makes you look very old). Anyway, just don’t want anyone else making that life-altering mistake. FUE only.

  9. Wheeler I have thought about an fue to fill my right side hair like and a few inches back but my hair loss is not stablized. Propecia isn’t as effective for me anymore after 16 years. I could get an fue but I’m afraid of future thinking around the new transplanted hair. Plus shockloss being a diffuse thinner. Remember nothing is 100% with these new treatments. They could all fail and disappear. Can’t rely on hope for new treatments to justify an ht. Plus 2025 is 6 years away. That’s a long time away.

    1. I feel as though the only real treatments soon will be regeneration / (maybe a drug way into the future to be of any use to achieve the proper hair coverage. Not this 10% garbage) !! Not to mention poisoning my amune system or playing with hormones as well.
      I think we’ll have some form of cloning by 2025. If not by then, well I’ll be shaving my head anyway till we do by that date- so Wheeler I hear you.
      # Slick – noted, FUE only for sure

      1. Not sure why my comments aren’t showing up on here. Anyways, ill try again…. Mjones what does this mean …”I could get an fue but I’m afraid of future thinking around the new transplanted hair” did you mean thinning not thinking? I 2025 isn’t really that far away… time goes by fast.
        The only thing I’m worried about when it comes to FUE is it not working and I am 10 grand in the hole with me same hair.

        1. They show up after I approve…can take a day if I am really busy. Sometimes, they automatically go to spam if the AI/algorithm thinks the link in there or some word in there or your IP or whatever else is suspicious. I rarely check the spam folder these days so those get deleted after a week or so automatically :-(

  10. Mjones…. what do you mean by your afraid of future thinking around the new transplanted hair? like do you think the transplanted hair will fall out if a new treatment comes out and you use it? Id just assume if a new treatment came out it would only add to the number of hairs around the transplanted area? or just don’t apply it to the area.
    I am close to pulling the trigger on a FUE…. Going to wait another year just to see if anything happens(it won’t).Obviously, I am concerned that the FUEi doesn’t work and I’m stuck 10 grand in the hole with the same hair I came in with.Another concern is that I get the FUE…. it looks amazing, fills in my balding spot (not completely bald yet)…. then my hair continues to fall out and I’m back at square 1 in 5 ish years and Id have to get another one… its not a disaster but Id rather not pay for 2 of them. My HOPE is that a maintenance or actual cure will be out within that 5 years. No offence to this URL name but if it happened in 2020 id be shocked and amazed.
    Hair transplants have come miles in the past years ….. Ive been on real self and other sites … some of the results are amazing. I see Hair Transplants taking a lot of negativity but at least they’re they only people releasing legitimate before and after pictures with the same angles and lighting.

  11. KROX20 protein, SCF gene. Interesting developments. I have found some relative success with Dutasteride and intermittent fasting.

  12. Tissue engineering of human hair follicles using a biomimetic developmental Approach

    Hasan Erbil Abaci, Abigail Coffman, Yanne Doucet, James Chen, Joanna Jacków, Etienne Wang, Zongyou Guo, Jung U. Shin, Colin A. Jahoda & Angela M. Christiano

    https://www.nature.com/articles/s41467-018-07579-y

    “Human DPC spheroids have the potential to induce de novo hair formation when placed in contact with human epidermis in mice”

    Again I must say the Pictures of Research are getting so much better now than the black and White pics from the past. … Interesting to see these sharp pics and then they fail to get a before/after pic with same light and angle in trials. :-)

      1. You are welcome! I am happy to share this when I see it. Especially when I read that People lose hope. ( I so understand that and it makes me sad) Look what development and what fantastic News in just few weeks!

        1. Didn’t Dr. Christiano leave jaks behind to pursue this research? That was my big clue that jak inhibitors wouldn’t work for everyone. I hope she cracks the code with this spheroid method!

          1. Slick unless christiano is going to get paid royalties from jak. This research she has with spheroids looks cool. But very early stages since it’s with mice. I like her and all but she just does research since 1998. No company or any trials. At least cots is working on bringing his research to market.

            Wheeler- sorry I meant thinning. Fue do look great but I’m afraid of hairs thinning behind or around new transplant hairs and end up looking worse. Plus my hair isn’t stabilized now. So I can get fue tomorrow then I’m 12 months I recede and thin more and playing catch. I think you need to read up more on ht. It’s not that simple. There are many factors. I see this one dude at my gym. Has a thick 3 inch hairline from fue bit lost all his hair behind it. Must have gotten full density fue and over harvested. The dude looks ridiculous. I really regeneration with wounding. No scars no transplants no down time. I’m seeing great results from many posters on hlt. Going to give than a try with 1.5 mm once a week. Maybe I can get some regrowth in my diffuse hair line.

    1. Key Quote from Study:

      “Hair restoration surgery to treat male and female pattern baldness usually requires 100 cm2 of donor tissue site to deliver nearly 2000 grafts (~4400 hairs) per patient. Using our strategy, we typically generate 15 million Dermal Papilla Cells (passage 3) from a strip of donor tissue as small as 0.5 cm2, yielding enough cells to produce more than 5000 Hair Follicles in our Human skin constructs, making it a feasible and efficient strategy to integrate with hair restoration therapy. The improvements of these robotic systems to harvest hair follicular units (groups of 1–4 hairs), as opposed to single hairs, yield significantly more hair growth per harvest. Using 3D-printing approaches, our goal is to engineer Hair follicles as follicular units and in desired patterns that can be integrated with surgical robots and facilitate effective hair transplantation surgery.”

      **Tsuji leading the pack, followed by, what’s that—I’m getting word that Columbia University is racing towards the finish line, will they make it**

      Quote: “Adaptation of this new technology by hair researchers, hair restoration surgeons and the pharmaceutical and cosmetic industries will have overwhelming implications in the maintenance and regeneration of this complex human tissue.”

      **this race is getting interesting ladies and gentlemen**

  13. Wow. What a paper!

    Very interesting line from the introduction:

    “Similarly, we recently reported that Jak inhibitors also directly restore hair inductivity in treated DPCs in culture”

    Everyone always dismisses JAK inhibitors because ‘AGA is not an immune system issue’.

    Maybe this will provide clarity into their method of action.

    This paper is well worth a read, this is leading to a potential rival to Tsuji, and JAK and Wnt pathways are discussed.

    I wonder if this method will be quick to market due to the fact that autologous cells are used? Similar to PRP?

    1. It’s from the study John Doe posted above:
      https://www.nature.com/articles/s41467-018-07579-y
      It’s from the Columbia University Team.
      ___

      Also Admin, here’s a new paper from an Iranian research team:

      Engineering the niche for hair regeneration — A critical review

      “Herein, we introduce the salient features, the hurdles that must be overcome, the hopes, and practical constraints to engineer stem cell niches for hair follicle regeneration.”

      https://www.sciencedirect.com/science/article/pii/S1549963418305161

      “Nanomedicine is able to facilitate hair follicle regeneration by stimulating specific cells. Nanomedicine offers a platform for the incorporation of useful biological molecules for the regeneration of hair follicle. It is expected that this growing technology will play a critical role in the advancement of hair regeneration in the near future.”

      See that… NEAR. FUTURE.

      “Microfluidic fabricated cell spheroids are homogeneous easy-to-use solutions for various applications which will be commercially in near future.”

      *mic drop* ; )

      1. Hi ,im Iranian
        Dr.Nilforoush in stem cell center of Iran claims they have started human trial regrow hair using dermal papila ….

  14. hair transplant in Iran is too cheap and there are some good hair transplant center here , its nice too see Iran and have a hair transplant

    1. @omid, but I am from one of the 3 countries that class as an enemy; the UK, the US and Canada, so it would take me 6 months to get a visa after the strictest checks have been made, plus I am not allowed to wander around the country independently and must be in an official tourist group at all times. I think I will go to Japan or London instead.

  15. I think I have given up complete hope.

    It’s all the same: new cure proven on rats human studies to occur sometime soon; everyone saying they can’t wait, then nothing ever happens with the “cure”. Rinse and repeat – several thousand times.

    Then there are the Products on the market where everyone states the exact same thing. I started using this new product and I am getting golden hairs and if they go terminal. Problem is its just the same posts year after year. Hard Earned Money flowing to phony cures.

    1. You’ve changed your tune Nasa? You have been telling everyone that JAK’s is the cure for the last few years without having a shred of scientific evidence. You have been adding to unpromised hope on this forum. You are probably the worst over-hyper on any hair loss forum. Get a grip you mug!

      1. I’m not God. And now I am tired of False Hope.

        I held in there for as long as possible, and yes JAK does work for baldness just Auto Immune baldness. And Yet we here about Costellis (sp?) forever, and Histogen, and these never pan out its just the same ole, same ole, wash, rinse, and repeat. False Hope with rat studies then rarely real tests on humans.

        We found out earlier this year that researchers could care less about hair loss that almost all of it is funny research as they care about “real cures for diseases”, and researching for hairloss is just a guise to get funding.

        1. With the amount of money that could be made with a real cure, it’s hard to understand why medical science wouldn’t take it seriously.

  16. I agree with NASA 100% It’s all the same news over and over. I’ve been hearing mouse hair growth cloning research since 2001. However we will get SM, Follica here in the usa. Follica claiming 4x better than current treatments which is what I would expect with a new generation treatment. I wouldn’t expect a full out cure for at least 10 years. Tsuji may be on the brink of hair cloning but the time he perfects it, get facilities world wide to offer it, and pass regulations in other countries etc it will be a while. It may be available in Japan between 2020 but imagine the wait list….could be years even for a consultation. Same scenario with Columbia University. They may be even longer since they haven’t started trials. Hope is great but let’s be realistic.

  17. I want NASA to be right about jaks. He overhyped it so much that in the world of karma it should come true with his positive energy. Just how I was about Cots and follica being awesome real treatments. NASA buddy, keep on with your positive hope about jak. It really does grow hair and we have seen evidence. Hang in there bro and I’ll keep pushing for cots. When they both get released we can come back here and say ” we were right we told you so” haha. Honesty though, at the end of the day I still believe in my conspiracy theory. The cure has been around probably since the 80s. They just like releasing treatments little by little that are increasingly better so they can make tons of cash. Whatever the next treatment is it won’t be the cure but a better treatment that will make millions until the next better treatment in 10 to 20 years from that etc. It’s an ongoing cycle just like all other treatmenta from diabetes, alzheimers, etc. Anywho I need to take my fin and rub some minox to save my diffuse ministuruzed hair. Enjoy your Sunday everyone. :)

  18. Tsuji and terskikh already “proved” the “cure” empirically ex vivo easy to forget. Organ cloning is real. that makes me wake up in the morning less nihlistic because the implications are beyond hair.

    Big pharma is absolutely terrible Obviously which makes me hardly judge anyone for conspiracies like that. But I’m gonna have to draw the line on the aga blackshelf cure lol. Aclaris is not colluding with the illuminati to suppress the real cure with endless JAK trials

    Mjones I remember having an afro at work on my cell phone laughing to tears 5 years ago arguing with you about your conspiracy theory. you remember that? Haha. Good ol days.

  19. Hahaha I can’t believe it’s been 5 years since our argument. Jeez man time really goes by quick. Those were definitely some fun times. I never asked, are you on finasteride or minox? Hopefully in the next years we will have a new treatment. That’s if the Illuminati allows it haha.

    1. Yeah man. Might have been 4 years…

      I got on topical fin about 3 months ago through empower pharmacy. Tried it all. Spironolactone fin mpb.org bs apple procyanidins tom hagerty garlic acv. I’m done. I’ll put anti androgen tinctures and topical fin on.

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