Wanted, dead and alive: Why a multidisciplinary approach is needed to unlock hair treatment potential

The final shape of a head hair is predetermined through a variety of factors during its formation in the follicle. These are genetic pathways, specific growth factors, cell differentiation and segregation, etc, with spatial as well as chronological dynamics. The cortex of hair consists of two major cell groups. These are characterized by parallel (para‐type) or roughly helical arrangements (ortho‐type) of the intermediate filaments (IF). There are also cell‐specific differences in the disulphide content, that is, of the cross‐link density of the IF‐associated matrix proteins. Given the current state of the academic discussion, we consider it as timely to support and broaden the view that, the structural differences of the cell types together with their lateral segregation are the main driving factor of curl formation. The mechanical effects, which derive thereof, are triggered in the transition zone of the follicle, that is, upon formation of the mature hair shaft. Furthermore, an irregular, “flat” cross section of the hair shaft is shown to be a synergistic but not determining factor of curl formation. The degree of cell type segregation along the mature hair shaft together with dynamic changes of the location of the plane of segregation, namely in a non‐circular cross section can account for very complex curl patterns. Against the background of these views, we argue that contributions to hair curl are implausible, if they relate to physical mechanisms which are active below the transition zone from the living to the mature (dead) hair.

Section: Discussionmentioning

confidence: 99%

Why is hair curly?—Deductions from the structure and the biomechanics of the mature hair shaft

Wortmann

Sripho

2019

“…The importance of PPAR‐γ signalling in dermal adipocytes for hair growth has also been demonstrated, when adipocyte‐specific PPAR‐γ delayed the formation of the hair coat in mice, while the use of PPAR‐γ antagonists abrogated adipogenesis in the skin and the activation of the HF stem cells in mice . Therefore, better understanding of the effects that PPAR‐γ signalling exerts specifically on the adipose tissue and dermal adipocytes is important to fully comprehend its roles in human HF and to more selectively target PPAR‐γ ligands to these specific skin compartments Different PPAR‐γ modulators can exert distinct human HF effects.…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

“…[119][120][121] Therefore, better understanding of the effects that PPAR-γ signalling exerts specifically on the adipose tissue and dermal adipocytes is important to fully comprehend its roles in human HF and to more selectively target PPAR-γ ligands to these specific skin compartments. [122] 2. Different PPAR-γ modulators can exert distinct human HF effects.…”

Section: Challeng E S and Future Per S Pec Tive Smentioning

confidence: 99%

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

Ramot

Bertolini

Boboljova

et al. 2019

Peroxisome proliferator‐activated receptors (PPARs) are abundantly expressed in human skin, with PPAR‐γ being the most intensively investigated isoform. In various ex vivo and in vivo models, PPAR‐γ‐mediated signalling has recently surfaced as an essential element of hair follicle (HF) development, growth and stem cell biology. Moreover, the availability of novel, topically applicable PPAR‐γ modulators with a favourable toxicological profile has extended the range of potential applications in clinical dermatology. In this review, we synthesize where this field currently stands and sketch promising future research avenues, focussing on the role of PPAR‐γ‐mediated signalling in the biology and pathology of human scalp HFs, with special emphasis on scarring alopecias such as lichen planopilaris and frontal fibrosing alopecia as model human epithelial stem cell diseases. In particular, we discuss whether and how pharmacological modulation of PPAR‐γ signalling may be employed for the management of hair growth disorders, for example, in scarring alopecia (by reducing HF inflammation as well as by promoting the survival and suppressing pathological epithelial‐mesenchymal transition of keratin 15 + epithelial stem cells in the bulge) and in hirsutism/hypertrichosis (by promoting catagen development). Moreover, we explore the potential role of PPAR‐γ in androgenetic alopecia, HF energy metabolism and HF ageing, and consider clinical perspectives that emanate from the limited data available on this so far. As this field of translational human hair research is still in its infancy, many open questions exist, for which we briefly delineate selected experimental approaches that promise to generate instructive answers in the near future.

“…Not only forensic scientists, but even the lay public are now well aware of the fact that plucked or cut hair shafts (HS) provide excellent source material for measuring and even timing the past systemic exposure of the human body to drugs (including drugs of abuse) and various toxins, including environmental toxins and heavy metals . Yet, even experts rarely reflect how and why these molecules get into the HS in the first place—and what this tells us about fundamental characteristics of this fascinating, cyclically remodelled mini‐organ …”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4] Yet, even experts rarely reflect how and why these molecules get into the HS in the first place-and what this tells us about fundamental characteristics of this fascinating, cyclically remodelled mini-organ. [4][5][6][7][8][9][10] In this Viewpoint essay, we discuss this often ignored and insufficiently examined key aspect of hair follicle (HF) biology and invite readers to entertain the provocative notion that this finding points to a more fundamentally important, but rarely contemplated function of HFs: to serve as primitive, multifocal excretory (mini-)organs which share surprisingly many functions with kidney physiology.…”

Section: Introductionmentioning

confidence: 99%

Do hair follicles operate as primitive, multifocal kidney‐like excretory (mini‐) organs?

Carre

Suzuki

Paus

2020

Besides their many other functions, hair shafts (HS) also are a repository for potentially noxious compounds. These are neutralized by their deposition within terminally differentiated, avital epithelial cells (trichocytes) that also facilitate the interaction of potential toxins with melanin, a toxin‐adsorbent biopolymer. Trichocytes are completely extruded via HS shedding during exogen, an actively controlled process. This underappreciated functional property of the human hair follicle (HF) makes it a bona fide excretory (mini‐) organ. Here, we ask whether the ca. 2 million HFs of the human integument operate in part as primitive, spatially dispersed kidney‐like excretory organs. Despite the many obvious differences between kidneys and HFs, this provocative hypothesis is also supported by other underappreciated renal‐follicular similarities such as anatomical parallels between Bowman's capsule and the anagen hair bulb, renal podocytes and HF winged cells ["Fuegelzellen"], and hypoxia‐dependent production of erythropoietin and extensive prostaglandin synthesis by human scalp HFs—just as in the kidney. The proposed kidney‐like excretory function of HFs may have constituted a major selection advantage of mammals during evolution and could be clinically relevant. We explain how the many open questions (eg, how are molecules destined to be excreted by hair shaft entrapment recognized, taken up and deposited into hair matrix cells?) can be tested experimentally. Finally, we explore how the therapeutic targeting of kidney‐like excretory HF functions may usefully complement classical nephrological therapy (dialysis) and ask whether stimulation of intrafollicular erythropoietin synthesis might become exploitable for the benefit of patients with renal anaemia.