Proliferation Of Dermal Papilla Cells Research Articles

Can Plant Extracts Help Prevent Hair Loss or Promote Hair Growth? A Review Comparing Their Therapeutic Efficacies, Phytochemical Components, and Modulatory Targets

This narrative review aims to examine the therapeutic potential and mechanism of action of plant extracts in preventing and treating alopecia (baldness). We searched and selected research papers on plant extracts related to hair loss, hair growth, or hair regrowth, and comprehensively compared the therapeutic efficacies, phytochemical components, and modulatory targets of plant extracts. These studies showed that various plant extracts increased the survival and proliferation of dermal papilla cells in vitro, enhanced cell proliferation and hair growth in hair follicles ex vivo, and promoted hair growth or regrowth in animal models in vivo. The hair growth-promoting efficacy of several plant extracts was verified in clinical trials. Some phenolic compounds, terpenes and terpenoids, sulfur-containing compounds, and fatty acids were identified as active compounds contained in plant extracts. The pharmacological effects of plant extracts and their active compounds were associated with the promotion of cell survival, cell proliferation, or cell cycle progression, and the upregulation of several growth factors, such as IGF-1, VEGF, HGF, and KGF (FGF-7), leading to the induction and extension of the anagen phase in the hair cycle. Those effects were also associated with the alleviation of oxidative stress, inflammatory response, cellular senescence, or apoptosis, and the downregulation of male hormones and their receptors, preventing the entry into the telogen phase in the hair cycle. Several active plant extracts and phytochemicals stimulated the signaling pathways mediated by protein kinase B (PKB, also called AKT), extracellular signal-regulated kinases (ERK), Wingless and Int-1 (WNT), or sonic hedgehog (SHH), while suppressing other cell signaling pathways mediated by transforming growth factor (TGF)-β or bone morphogenetic protein (BMP). Thus, well-selected plant extracts and their active compounds can have beneficial effects on hair health. It is proposed that the discovery of phytochemicals targeting the aforementioned cellular events and cell signaling pathways will facilitate the development of new targeted therapies for alopecia.

Injectable platelet-rich fibrin promotes proliferation and trichogenic inductivity of dermal papilla cells through activating TGF-β/Smad signaling pathway.

Dermal papilla cell (DPC) belongs to a specialized mesenchymal stem cell for hair follicle regeneration. Maintaining the ability of DPCs to stimulate hair in vitro culture is important for hair follicle morphogenesis and regeneration. As the third generation of platelet concentrate, injectable platelet-rich fibrin (i-PRF) is a novel biomaterial containing many growth factors and showing promising effects on tissue reconstruction. We aimed to explore the influences of i-PRF on the proliferative, migratory, as well as trichogenic ability of DPCs and compared the effects of i-PRF and platelet-rich plasma (PRP), the first generation of platelet concentrate. Both PRP and i-PRF facilitated DPCs proliferation, and migration, along with trichogenic inductivity as well as stimulated the TGF-β/Smad pathway, while the impacts of i-PRF were more significant than PRP. A small molecule inhibitor of TGF-beta receptor I, Galunisertib, was also applied to treat DPCs, and it rescued the impacts of i-PRF on the proliferative, migratory, trichogenic inductivity, and proteins-associated with TGF-β/Smad pathway in DPCs. These findings revealed that i-PRF had better effects than PRP in enhancing the proliferative, migratory, and hair-inducing abilities of DPCs by the TGF-β/Smad pathway, which indicated the beneficial role of i-PRF in hair follicle regeneration.

Melatonin promotes proliferation of Inner Mongolia cashmere goat hair follicle papilla cells through Wnt10b

The study demonstrated that melatonin (MT) can induce the development of secondary hair follicles in Inner Mongolian cashmere goats through the Wnt10b gene, leading to secondary dehairing. However, the mechanisms underlying the expression and molecular function of Wnt10b in dermal papilla cells (DPC) remain unknown. This research aimed to investigate the impact of MT on DPC and the regulation of Wnt10b expression, function, and molecular mechanisms in DPC. The findings revealed that MT promotes DPC proliferation and enhances DPC activity. Co-culturing DPC with overexpressed Wnt10b and MT showed a significant growth promotion. Subsequent RNA sequencing (RNA-seq) of overexpressed Wnt10b and control groups unveiled the regulatory role of Wnt10b in DPC. Numerous genes and pathways, including developmental pathways such as Wnt and MAPK, as well as processes like hair follicle morphogenesis and hair cycle, were identified. These results suggest that Wnt10b promotes the growth of secondary hair follicles in Inner Mongolian cashmere goats by regulating crucial factors and pathways in DPC proliferation.

Regulation of Hair Follicle Growth and Development by Different Alternative Spliceosomes of FGF5 in Rabbits.

This study investigated the regulatory effect of alternative spliceosomes of the fibroblast growth factor 5 (FGF5) gene on hair follicle (HF) growth and development in rabbits. The FGF5 alternative spliceosomes (called FGF5-X1, FGF5-X2, FGF5-X3) were cloned. The overexpression vector and siRNA of spliceosomes were transfected into dermal papilla cells (DPCs) to analyze the regulatory effect on DPCs. The results revealed that FGF5-X2 and FGF5-X3 overexpression significantly decreased LEF1 mRNA expression (p < 0.01). FGF5-X1 overexpression significantly reduced CCND1 expression (p < 0.01). FGF5-X1 and FGF5-X2 possibly downregulated the expression level of FGF2 mRNA (p < 0.05), and FGF5-X3 significantly downregulated the expression level of FGF2 mRNA (p < 0.01). The FGF5 alternative spliceosomes significantly downregulated the BCL2 mRNA expression level in both cases (p < 0.01). FGF5-X1 and FGF5-X2 significantly increased TGFβ mRNA expression (p < 0.01). All three FGF5 alternative spliceosomes inhibited DPC proliferation. In conclusion, the expression profile of HF growth and development-related genes can be regulated by FGF5 alternative spliceosomes, inhibiting the proliferation of DPCs and has an influence on the regulation of HF growth in rabbits. This study provides insights to further investigate the mechanism of HF development in rabbits via FGF5 regulation.

Nanocrystal Structure of Minoxidil: A Safe Stimulator for Hair Growth Factor for C57BL/6 Mice.

Commercial Minoxidil (MXD) is commonly used as a vasodilator agent of hair follicles for providing direct dermal papilla cell proliferation and consequently enhancing the rate of hair growth. The current study attempted to improve the bioactivity and water solubility of MXD by producing nanocrystal structures and investigating the obtained hair growthstimulating activity on C57BL/6 mice. The MXD nanoparticles (MXD-NPs) were prepared through a bead mill and ultrasonic process and characterized by DLS, XRD, UV-Vis, FTIR, FESEM, TEM, and Zeta-potential techniques. The cytotoxicity of MXD-NPs was studied on human dermal fibroblast (HDF) by MTT assay. Lastly, we analyzed the comparative hair growth inductive activity of certain MXD-NPs concentrations on C57BL/6 mice. The stabled MXD-NPs (-46 mV, 21.9 nm) caused a significant increase in the hair growth rate of C57BL/6 mice by running a safe site-specific delivery mechanism on the targeted pilosebaceous follicles when compared to MXD. The MXD-NPs-receiving mice exhibited a greater rate of anagen/telogen follicular when compared with MXD-treated types, which verified the improvement of their hair re-growing and follicular-stimulative activities. Therefore, these outcomes confirmed the potential of MXD-NPs for substituting its commercial solution format as a safe and efficient iso-formulation structure.

Epidermal ET-1 signal induces activation of resting hair follicles by upregulating the PI3K/AKT pathway in the dermis.

The prevalence of alopecia has increased recently. Hair loss is often accompanied by the resting phase of hair follicles (HFs). Dermal papilla (DP) plays a crucial role in HF development, growth, and regeneration. Activating DP can revive resting HFs. Augmenting WNT/β-catenin signaling stimulates HF growth. However, the factors responsible for activating resting HFs effectively are unclear. In this study, we investigated epidermal cytokines that can activate resting HFs effectively. We overexpressed β-catenin in both invivo and invitro models to observe its effects on resting HFs. Then, we screened potential epidermal cytokines from GEO DATASETs and assessed their functions using mice models and skin-derived precursors (SKPs). Finally, we explored the molecular mechanism underlying the action of the identified cytokine. The results showed that activation of WNT/β-catenin in the epidermis prompted telogen-anagen transition. Keratinocytes infected with Ctnnb1-overexpressing lentivirus enhanced SKP expansion. Subsequently, we identified endothelin 1 (ET-1) expressed higher in hair-growing epidermis and induced the proliferation of DP cells and activates telogen-phase HFs invivo. Moreover, ET-1 promotes the proliferation and stemness of SKPs. Western blot analysis and invivo experiments revealed that ET-1 induces the transition from telogen-to-anagen phase by upregulating the PI3K/AKT pathway. These findings highlight the potential of ET-1 as a promising cytokine for HF activation and the treatment of hair loss.

SP1 and KROX20 Regulate the Proliferation of Dermal Papilla Cells and Target the CUX1 Gene

Previous studies have demonstrated that CUX1 could contribute to the proliferation of DPCs in vitro, but the upstream transcriptional regulatory mechanisms of CUX1 remain largely unknown. This study aimed to investigate the upstream transcriptional regulators of CUX1 to enhance our comprehension of the mechanism of action of the CUX1 gene in ovine DPCs. Initially, the JASPAR (2024) software was used to predict the upstream target transcription factors for the CUX1 gene. Subsequently, through RT-qPCR and a double luciferase reporter assay, the interaction between SP1, KROX20, and CUX1 was established, respectively. The results indicated that SP1 and KROX20 were two highly reliable upstream transcription regulators for the CUX1 gene. Additionally, we found that SP1 promoted the proliferation of DPCs by overexpressing SP1 in DPCs, and KROX20 inhibited the proliferation of DPCs by overexpressing KROX20 in DPCs. These findings are also consistent with the transcriptional regulation of CUX1 by SP1 and KROX20, respectively. This study suggests that the effect of DPC proliferation in vitro by CUX1 may regulated by the transcription factors SP1 and KROX20.

Ginsenosides in Panax ginseng Extract Promote Anagen Transition by Suppressing BMP4 Expression and Promote Human Hair Growth by Stimulating Follicle-Cell Proliferation.

Studies showing that Panax ginseng promotes hair growth have largely been conducted using mice; there are few reports on how P. ginseng affects human hair growth. In particular, little is known about its effect on the telogen to anagen transition. To determine the effect of P. ginseng on human hair growth and the transition from the telogen to the anagen phase. The effects of P. ginseng extract (PGE) and the three major ginsenoside components, Rb1, Rg1, and Re, on the proliferation of human dermal papilla cells (DPCs) and human outer root sheath cells (ORSCs) were investigated. The effects of these compounds on the cell expression of bone morphogenetic protein 4 (BMP4), fibroblast growth factor 18 (FGF18) and Noggin were assessed by real-time PCR. The effect of PGE on hair-shaft elongation was determined in a human hair follicle organ-culture system. PGE and the three ginsenosides stimulated the proliferation of DPCs and ORSCs and suppressed BMP4 expression in DPCs but did not affect FGF18 expression in ORSCs and Noggin expression in DPCs. PGE stimulated hair-shaft growth. PGE and the ginsenosides Rb1, Rg1, and Re stimulate the transition from the telogen phase to anagen phase of the hair cycle by suppressing BMP4 expression in DPCs. These compounds might be useful for promoting the growth of human hair.

SOX18 Promotes the Proliferation of Dermal Papilla Cells via the Wnt/β-Catenin Signaling Pathway.

SRY-box transcription factor 18 (SOX18) is known to play a crucial role in the growth and development of hair follicles (HF) in both humans and mice. However, the specific effect of SOX18 on sheep hair follicles remains largely unknown. In our previous study, we observed that SOX18 was specifically expressed within dermal papilla cells (DPCs) in ovine hair follicles, leading us to investigate its potential role in the growth of hair follicles in sheep. In the present study, we aimed to examine the effect of SOX18 in DPCs and preliminarily study its regulatory mechanism through RNA-seq. We initially found that the overexpression of SOX18 promoted the proliferation of DPCs compared to the negative control group, while the interference of SOX18 had the opposite effect. To gain further insight into the regulatory mechanism of SOX18, we conducted RNA-seq analysis after knocking down SOX18 in Hu sheep DPCs. The result showed that the Wnt/β-Catenin signaling pathway was involved in the growth process of DPC after SOX18 knockdown. Subsequently, we investigated the effect of SOX18 on the Wnt/β-Catenin signaling pathway in DPCs using TOP/FOP-flash, qRT-PCR, and Western blot (WB) analysis. Our data demonstrated that SOX18 could activate the Wnt/β-Catenin signaling pathway in DPCs. Additionally, we observed that SOX18 could rescue the proliferation of DPCs after inhibiting the Wnt/β-Catenin signaling pathway. These findings underscore the essential role of SOX18 as a functional molecule governing the proliferation of DPCs. Additionally, these findings also greatly enhance our understanding of the role of SOX18 in the proliferation of DPCs and the growth of wool in Hu sheep.

JUNB affects hair follicle development and regeneration by promoting the proliferation of dermal papilla cells in goat

Abstract Background The process of hair follicle morphogenesis, development, and regeneration essentially depends on the interaction between skin epidermis and dermis, while dermal papilla (DP) cells play a vital role in this process. Transcription factors recognize specific DNA sequences to regulate gene transcription during hair follicle development. Our previous sequencing data have demonstrated that JUNB is differentially expressed between the induction and differentiation stages during hair follicle development of cashmere goat. However, the underlying mechanism of JUNB currently remains unknown. Results The function of JUNB on DP cells was explored by EdU, MTT, CCK-8, and flow cytometry analysis, which showed that JUNB significantly promoted the cell viability and proliferation. Subsequently, the underlying regulation mechanism of JUNB was investigated. The dual-luciferase reporter assay and RT-qPCR results revealed that TCF3 was a target gene of JUNB. And the expressions of Wnt signaling pathway-related genes, CTNNB1 (β-catenin), Cyclin D1, and C-myc, were significantly promoted at mRNA and protein levels. The homology analysis based on JUNB protein sequences revealed that goat and mouse had high homology among 11 species. Therefore, C57 BL/6 mice were selected as the animal model for further in vivo experiment. The result showed that JUNB promoted hair regeneration of mouse, and the HE and immunofluorescence staining results of skin tissues further proved it. Conclusions Taken together, our results revealed that JUNB promoted the proliferation of DP cells by regulating Wnt signaling pathway, thereby affecting hair regeneration, which would provide molecular target for improving cashmere quality and breeding of cashmere goats. Graphical Abstract

Combatting ageing in dermal papilla cells and promoting hair follicle regeneration using exosomes from human hair follicle dermal sheath cup cells.

Dermal papilla cells (DPCs) undergo premature ageing in androgenetic alopecia and senescent alopecia. As critical components of hair follicle reconstruction, DPCs are also prone to senescence invitro, resulting in a diminished hair follicle inductivity capacity. Dermal sheath cup cells (DSCCs), a specific subset of hair follicle mesenchymal stem cells, intimately linked to the function of DPCs. The primary objective of this research is to investigate the anti-ageing effect of exosomes derived from DSCCs (ExoDSCCs ) on DPCs. Exosomes were utilized to treat H2 O2 -induced DPCs or long-generation DPCs(P10). Our findings demonstrate that ExoDSCCs(P3) promote the proliferation, viability and migration of senescent DPCs while inhibiting cell apoptosis. The expression of senescence marker SA-β-Gal were significantly downregulated in senescent DPCs. When treated with ExoDSCCs(P3) , expression of inducibility related markers alkaline phosphatase and Versican were significantly upregulated. Additionally, ExoDSCCs(P3) activated the Wnt/β-catenin signalling invitro. In patch assay, ExoDSCCs(P3) significantly promoted hair follicle reconstruction in senescent DPCs. In summary, our work highlights that ExoDSCCs(P3) may restore the biological functions and improve the hair follicle induction ability of senescent DPCs. Therefore, ExoDSCCs(P3) may represent a new strategy for intervening in the ageing process of DPCs, contributing to the prevention of senile alopecia.

ChIP-Seq analysis reveals PRKACB as a target gene of HOXC13 involved in rabbit hair follicle development

Dermal papilla cells (DPCs) are key regulators of hair follicle (HF) development and growth, which not only regulate HF growth and cycling but play a role in the pathogenesis of hair loss. The transcription factor Homeobox C13 (HOXC13) can modulate the growth and development of HFs. Nevertheless, the specific genes and pathways regulated by HOXC13 in DPCs have yet to be determined. Thus, to gain a better understanding of genomic binding sites involved in HOXC13-regulated HF development, chromatin immunoprecipitation followed by high throughput sequencing (ChIP-Seq) was performed on rabbit DPCs with pcDNA3.1–3 × Flag-HOXC13 overexpression. A complete set of 9670 enrichment peaks was acquired by applying HOXC13-Flag ChIP. Subsequently, the peak sequence was annotated to the rabbit genome, revealing that 6.1 % of the peaks were identified within in the promoter region. Thereafter, five annotated genes were verified using RT-qPCR. The peak-associated genes were mainly enriched in signaling pathways related to HF development, such as MAPK and PI3K-Akt. Furthermore, by using a dual-luciferase reporter assay, we found that HOXC13 can target the protein kinase cAMP‑dependent catalytic β (PRKACB) promoter region (-1596 ∼ -1107 bp) and inhibit its transcription, which was consistent with data obtained from ChIP-seq analysis. Overexpression of PRKACB gene significantly modulated the expression of BCL2, WNT2, LEF1, and SFRP2 genes related to HF development as determined by RT-qPCR (P < 0.01, P < 0.05). The CCK-8 and flow cytometry assays showed that PRKACB significantly inhibited the proliferation of DPCs and promoted apoptosis (P < 0.01). In conclusion, our research revealed that PRKACB has the potential to serve as a novel target gene of HOXC13, contributing to the regulation of the proliferation and apoptosis of DPCs. The process of identifying global target genes can contribute to the understanding of the intricate pathways that HOXC13 regulates in the growth of HFs.

MiR-199a-5p inhibits dermal papilla cells proliferation by regulating VEGFA expression in cashmere goat

Hair follicles undergo a renewal cycle consisting of anagen, telogen and catagen stages. MicroRNA (miRNA) plays a crucial role in this process. Recent studies have shown that miR-199a-5p, which exhibits differential expression between anagen and telogen stages in the hair follicle cycle of cashmere goats, inhibits the proliferation of various cell types, including skin keratinocytes and vascular endothelial cells. Since the proliferation of dermal papilla cells (DPCs) is a key factor in the hair follicle cycle, we utilized DPCs to investigate the function and molecular mechanism of miR-199a-5p in cashmere goats. Our functional analysis revealed that miR-199a-5p significantly suppressed cell viability and proliferation of DPCs, as evidenced by MTT, EdU and RT-qPCR methods. Subsequently, we investigated the regulatory mechanism of miR-199a-5p. Through bioinformatics analysis, a potential correlation between lnc102173187 and miR-199a-5p was predicted. However, the dual luciferase reporter assay revealed no interaction between lnc102173187 and miR-199a-5p. Further investigation using dual-luciferase reporter assay, RT-qPCR, and western blot results confirmed that VEGFA was the target gene of miR-199a-5p from. The functional experiment demonstrated that VEGFA promoted the proliferation of DPCs, and antagonized the inhibitory effect of miR-199a-5p on DPCs proliferation. Taken together, this research revealed the role of miR-199a-5p and VEGFA on the proliferation of dermal papilla cells in cashmere goat, which would enrich the theoretical basis for hair follicle development, and could also serve as a marker cofactor to play an important reference and guidance role in the breeding, improvement and optimization of cashmere goat breeds.

Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopecia

BackgroundAndrogenetic alopecia (AGA) is one of the most common hair loss diseases worldwide. However, current treatments including medicine, surgery, and stem cells are limited for various reasons. Cell-free fat extract (CEFFE), contains various cell factors, may have potential abilities in treating AGA. This study aims to evaluate the safety, effectiveness and the underlying mechanism of CEFFE in treating AGA.MethodsSex hormone evaluation, immunogenicity assay and genotoxicity assay were conducted for CEFFE. In vivo study, male C57BL/6 mice were injected subcutaneously with dihydrotestosterone (DHT) and were treated with different concentration of CEFFE for 18 days (five groups and n = 12 in each group: Control, Model, CEFFELow, CEFFEMiddle, CEFFEHigh). Anagen entry rate and hair coverage percentage were analyzed through continuously taken gross photographs. The angiogenesis and proliferation of hair follicle cells were evaluated by hematoxylin–eosin, anti-CD31, and anti-Ki67 staining. In vitro study, dermal papilla cells (DPCs) were incubated with different concentrations of CEFFE, DHT, or CEFFE + DHT, followed by CCK-8 assay and flow cytometry to evaluate cell proliferation cycle and apoptosis. The intracellular DHT level were assessed by enzyme-linked immunosorbent assay. The expression of 5α-reductase type II, 3α-hydroxysteroid dehydrogenase and androgen receptor were assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or/and western blot.ResultsIn CEFFE-treated mice, an increase in the anagen entry rate and hair coverage percentage was observed. The number of CD31-positive capillaries and Ki67-positive cells were increased, suggesting that CEFFE promoted the proliferation of DPCs, modulated the cell cycle arrest, inhibited apoptosis caused by DHT, reduced the intracellular concentration of DHT in DPCs, and downregulated the expression of AR.ConclusionsCEFFE is a novel and effective treatment option for AGA through producing an increased hair follicle density and hair growth rate. The proposed mechanisms are through the DHT/AR pathway regulation and regional angiogenesis ability.

Vitamin A regulates dermal papilla cell proliferation and apoptosis under heat stress via IGF1 and Wnt10b signaling

Heat stress (HS) negatively affects the development of hair follicles. The present study investigated the effect of vitamin A (VA) on the development of rabbit dermal papilla cells (DPCs) under HS and the underlying regulatory mechanisms. Addition of 0.4 mg/L VA to the culture medium significantly enhanced cell proliferation (P < 0.001) and inhibited the apoptosis of DPCs (P < 0.01). VA decreased the proportion of DPCs in G0/G1 stage of the cell cycle under HS along with the expression of caspase 3, heat shock protein 70 (HSP70), and microRNA 195 (miR-195) (P < 0.05). VA also activated the insulin-like growth factor 1 (IGF1) and Wnt10b/β-catenin signaling pathways. The results of the dual luciferase reporter assay showed that IGF1 expression was modulated by miR-195–5p. Over-expression of miR-195–5p in DPCs with HS+VA treatment significantly reduced cell viability and IGF1 signaling (P < 0.01) and increased apoptosis (P < 0.01) compared with the HS+VA group. The positive effects of VA on proliferation and apoptosis of DPCs under HS were significantly attenu-ated by blocking Wnt10b and β-catenin signaling with IWP-2 and XAV-939, respectively. These results demonstrate that VA can promote hair follicle development following HS via modulation of miR-195/IGF1 and Wnt10b/β-catenin signaling pathways.

CRABP2 Promotes the Proliferation of Dermal Papilla Cells via the Wnt/β-Catenin Pathway

In our previous study of Hu sheep hair follicles, we found that CRABP2 was highly expressed in DPCs, which suggested that CRABP2 may influence the number of DPCs. In the present study, we aimed to understand the effect of CRABP2 in Hu sheep dermal papilla cells (DPCs). First, we explored the influence of CRABP2 on the ability of Hu sheep DPCs’ proliferation. Based on the results obtained from some experiments, such as CCK-8, EDU, qPCR, and Western blot experiment, we found that the overexpression of CRABP2 facilitated the proliferation of DPCs compared to the negative control group. Then, we also detected the effect of CRABP2 on the Wnt/β-catenin pathway based on the important function of the Wnt/β-catenin pathway in hair follicles. The results showed that CRABP2 could activate the Wnt/β-catenin pathway in DPCs, and it rescues the proliferation of DPCs when the Wnt/β-catenin pathway was inhibited. In summary, our findings indicate that CRABP2 is a vital functional gene in the proliferation of Hu sheep DPCs. Our study will be of great use for revealing the roles of CRABP2 in the hair follicles of Hu sheep.

Regulatory Effects of FGF9 on Dermal Papilla Cell Proliferation in Small-Tailed Han Sheep.

Fibroblast growth factor 9 (FGF9) is crucial for the growth and development of hair follicles (HFs); however, its role in sheep wool growth is unknown. Here, we clarified the role of FGF9 in HF growth in the small-tailed Han sheep by quantifying FGF9 expression in skin tissue sections collected at different periods. Moreover, we evaluated the effects of FGF9 protein supplementation on hair shaft growth in vitro and FGF9 knockdown on cultured dermal papilla cells (DPCs). The relationship between FGF9 and the Wnt/β-catenin signaling pathway was examined, and the underlying mechanisms of FGF9-mediated DPC proliferation were investigated. The results show that FGF9 expression varies throughout the HF cycle and participates in wool growth. The proliferation rate and cell cycle of FGF9-treated DPCs substantially increase compared to that of the control group, and the mRNA and protein expression of CTNNB1, a Wnt/β-catenin signaling pathway marker gene, is considerably lower than that in the control group. The opposite occurs in FGF9-knockdown DPCs. Moreover, other signaling pathways are enriched in the FGF9-treated group. In conclusion, FGF9 accelerates the proliferation and cell cycle of DPCs and may regulate HF growth and development through the Wnt/β-catenin signaling pathway.

Dietary marine-derived ingredients for stimulating hair cell cycle

In normal condition human hair growth occurs through three phases, anagen (growth phase included about 85 % of hairs, last from 2 to 6 years), catagen (transitional phase lasting up to 2 weeks) and telogen (resting phase which last from 1 to 4 months). Natural dynamics of the hair growth process can be impaired by several factors, such as genetic predisposition, hormonal disorders, aging, poor nutrition or stress, which can lead to the slowdown in the growth of hair or even hair loss. The aim of the study was to assess the hair growth promotion effect of marine-derived ingredients, hair supplement Viviscal® and its raw components (marine protein complex AminoMarC®, shark and oyster extract). Cytotoxicity, production of alkaline phosphatase and glycosaminoglycans, as well as expression of genes involved in hair cycle-related pathways were investigated using dermal papilla cells, both immortalized and primary cell lines. Tested marine compounds showed no evidence of cytotoxicity under in vitro conditions. Viviscal® significantly increased proliferation of dermal papilla cells. Moreover, tested samples stimulated cells to produce alkaline phosphatase and glycosaminoglycans. Increased expression of hair cell cycle-related genes was also observed. The obtained results indicate that marine-derived ingredients stimulate hair growth through anagen activation.

Dermal Papilla Cell Proliferation of Phytochemicals Isolated from Chestnut Shells (Castanea crenata)

Castanea crenata (Fagaceae) is a species of chestnut tree that is endemic to the Republic of Korea and Japan. While its kernels are consumed, chestnut by-products such as shells and burs, which account for 10-15% of the total weight, are discarded as waste. Phytochemical and biological studies have been carried out to eliminate this waste and develop high-value products from its by-products. In this study, five new compounds (1-2, 6-8) along with seven known compounds were isolated from the shell of C. crenata. This is the first study to report diterpenes from the shell of C. crenata. Comprehensive spectroscopic data including 1D, 2D NMR, and CD spectroscopy were used to determine the compound structures. All isolated compounds were examined for their ability to stimulate dermal papilla cell proliferation using a CCK-8 assay. In particular, 6β,7β,16α,17-Tetrahydroxy-ent-kauranoic acid, isopentyl-α-L-arabinofuranosyl-(1→6)-β-D-glucopyranoside, and ellagic acid exhibited the most potent proliferation activity of all.

Cold atmospheric microwave plasma (CAMP) stimulates dermal papilla cell proliferation by inducing β-catenin signaling

Hair loss or alopecia is an unpleasant symptom that exacerbates an individual's self-esteem and requires appropriate treatment. The Wnt/β-catenin signaling is a central pathway that promotes dermal papilla induction and keratinocyte proliferation during hair follicle renewal. GSK-3β inactivated by its upstream Akt and ubiquitin-specific protease 47 (USP47) has been shown to inhibit β-catenin degradation. The cold atmospheric microwave plasma (CAMP) is microwave energy enriched with mixtures of radicals. CAMP has been reported to have antibacterial and antifungal activities with wound healing activity against skin infection; however, the effect of CAMP on hair loss treatment has not been reported. We aimed to investigate the effect of CAMP on promoting hair renewal in vitro and to elucidate the molecular mechanism, targeting β-catenin signaling and YAP/TAZ, the co-activators in the Hippo pathway, in human dermal papilla cells (hDPCs). We also evaluated plasma effects on the interaction between hDPCs and HaCaT keratinocytes. The hDPCs were treated with plasma-activating media (PAM) or gas-activating media (GAM). The biological outcomes were determined by MTT assay, qRT-PCR, western blot analysis, immunoprecipitation, and immunofluorescence. We found that β-catenin signaling and YAP/TAZ were significantly increased in PAM-treated hDPCs. PAM treatment also induced β-catenin translocation and inhibited β-catenin ubiquitination by activating Akt/GSK-3β signaling and upregulating USP47 expression. In addition, hDPCs were more aggregated with keratinocytes in PAM-treated cells compared with control. HaCaT cells cultured in a conditioned medium derived from PAM-treated hDPCs exhibited an enhancing effect on activating YAP/TAZ and β-catenin signaling. These findings suggested that CAMP may be a new therapeutic alternative for alopecic treatment.