This Explains The Hairloss Pattern! Also sh*t Might Be Irreversible!

[EndlessPossibilities]

We hypothesized that bulge-arrector pili muscle interactions might involve epidermal basement membrane components. Laminin-511 has been shown to mediate epidermal-dermal papilla signaling during hair development (Gao et al., 2008), and in a range of other tissues, such as kidney and pancreas, the basement membrane is involved in bidirectional cellular interactions (Linton et al., 2007, Nikolova et al., 2006). Furthermore, the basement membrane of the skin exhibits local variation in structure and composition (Timpl, 1996). Such basement membrane heterogeneity would not only provide a potential mechanism for anchoring different stem cell populations in different regions of the epidermis, but could also result in local differences in signaling with adjacent mesenchymal cells (Akiyama et al., 1995, Fuchs, 2008, Spradling et al., 2001, Watt and Hogan, 2000).

Gene expression profiling of the bulge compartment has revealed that bulge stem cells express a number of extracellular matrix (ECM) proteins that are distinct from those of other epidermal cells (Morris et al., 2004, Ohyama et al., 2006, Tumbar et al., 2004). One of these is nephronectin, an ECM protein with five EGF-like repeats, an RGD sequence, and a COOH-terminal MAM domain(Brandenberger et al., 2001). Nephronectin is an interesting candidate mediatorof epidermal interactions with mesenchymal cells because the nephronectin receptor is α8β1 (Brandenberger et al., 2001, Sato et al., 2009), an integrin that is expressed in the dermal papilla, but not by adult epidermal keratinocytes(Driskell et al., 2009, Watt, 2002). Furthermore, the epithelial-mesenchymal interactions that are required for kidney organogenesis are disrupted in mice lacking α8β1 or nephronectin (Brandenberger et al., 2001, Linton et al., 2007, Müller et al., 1997).

In this study, we show that bulge stem cells create a specialized basement membrane containing nephronectin, which induces arrector pili muscle differentiation and anchorage to the bulge. Loss of nephronectin or α8 integrin expression causes delocalization of the APM. Thus, the bulge ECM not only contributes to the specialized niche of hair follicle stem cells, but also provides a niche for smooth muscle progenitors.

https://www.sciencedirect.com/science/article/pii/S0092867411000158

https://www.oatext.com/pdf/BEM-2-122.pdf


Dexamethasone. !

I read a report of a guy who saw his hair thicken up on it on raypeat forum. Also they have a combination of dexamethasone and alfatradiol for hair

 

[DavidsDome]

We also examined the effects of BMP and Notch signaling on nephronectin expression (Figures S5B and S5C). Inhibition of BMP signaling by expression of the BMP antagonist Noggin under the control of the K14 promoter (Sharov et al., 2009) increased nephronectin expression in the bulge. However, activation of Notch signaling by expression of the Notch intracellular domain via the K14 promoter (Estrach et al., 2006) did not affect nephronectin expression. The upregulation of nephronectin in K14Noggin skin fits well with the upregulation of Wnt signaling that occurs on BMP inhibition in this model (Sharov et al., 2009). These results indicate that activation of Wnt/β-catenin signaling in the bulge and hair germ induces nephronectin expression, whereas Wnt/β-catenin signaling in the interfollicular epidermis normally suppresses nephronectin.

To determine whether epidermal β-catenin activation was sufficient to induce α8β1 expression in adjacent dermal cells, we examined 4-OHT-treated mice expressing the ΔNβ-cateninER transgene. When Wnt/β-catenin signaling was activated in K14ΔNβ-cateninER transgenic mice, α8 integrin was ectopically expressed by dermal cells adjacent to ectopic hair follicles, colocalizing with nephronectin (Figures 6J–6L). When β-catenin was selectively activated in bulge stem cells by 4-OHT treatment of K15ΔNβ-cateninER mice (Baker et al., 2010), nephronectin was upregulated in the bulge and there was a corresponding increase in bulge-associated α8 integrin-expressing dermal cells (Figures 6M and 6N). These observations establish that epidermal Wnt/β-catenin signaling induces expression of α8 integrin in adjacent dermal cells.

Taken together, our data show that nephronectin is a Wnt/β-catenin target gene and that Wnt/β-catenin signaling in epidermis determines not only region-specific nephronectin deposition, but also, as a result, the location of α8 integrin-expressing mesenchymal cells.

https://www.sciencedirect.com/science/article/pii/S0092867411000158

 

[DavidsDome]

https://www.oatext.com/pdf/BEM-2-122.pdf


Dexamethasone. !

I read a report of a guy who saw his hair thicken up on it on raypeat forum. Also they have a combination of dexamethasone and alfatradiol for hair

Glucocorticoid effect on hair growth initiation: a reconsideration.
Stenn KS1, Paus R, Dutton T, Sarba B.
Author information

Abstract
It has been demonstrated by various workers in the past that glucocorticosteroids block hair growth. Using the mouse model for studying hair growth induction we reexamined the effect of topically applied steroids on hair growth to establish at what stage the steroid block acts. In accord with studies by others, we found that these steroids block hair growth at the point of anagen initiation, but that once the steroid applications are stopped, hair growth starts. Since steroid withdrawal alone did not induce hair growth, it is clear that these steroids do not block, either spontaneous or manipulated, hair growth induction, but they do block, the apparent next step, i.e., hair formation. Moreover, since hair growth could be induced even while the animals were being treated with the steroid, the induction step appears independent of the steroid block. These studies and those of others lead us to conclude that these steroids block the expression of hair-forming genes, but do not interfere with the signal(s) that initiates those genes. This system appears to be ideal for identifying the signals (perhaps, genes) responsible for initiating hair growth.

https://www.ncbi.nlm.nih.gov/pubmed/8352950

Not sure if this applies to all corticosteroids though...
Because Clobetasol stimulates Smoothened (Sonic Hedgehod), which should be a positive thing...

 

[HansMetjen]

My goal with MB is to restore mitochondrial function.

Is that possible?

I have restless legs syndrome which might be the effect of mitochondrial dysfunction (iron metabolism in mitochondria). Maybe I should try Methylene Blue? Although iron supplements help quite well in extinguishing my RLS.

 

[TheHawk]

norepinephrine interesting

so that stimulates the erector pili muscles for Hair ?

Wimhof breathing is an easy way to release a sh*t ton of norepinephrine without sky diving.

 

[TheHawk]

Good information but the conclusion is dumb OP.

This is just another down chain aspect of hair loss.

Skull expansion, scalp tension, and fluid pressure are not disproved by this.

Plus I’ve seen some legitimately insane regrowth by a variety of methods.

For any balding guys standards, “regrowth” is 100,000% possible.