Significance In the inner ear, the sensory receptor cells (hair cells) signal reception of sound. They do so by converting mechanical input, due to sound waves moving the hair bundles on these cells, ...into electrical current through ion channels situated at the tips of the bundles. To keep the receptors operating at their maximum sensitivity, the current declines rapidly, a process known as adaptation. In nonmammalian vertebrates, Ca ²⁺ ions entering the mechanosensitive ion channels drive adaptation, but it has been questioned whether this mechanism applies to mammals. We show that adaptation in mammalian cochlear hair cells is, as in other vertebrates, driven by Ca ²⁺ entry, demonstrating the importance of this process as a fundamental mechanism in vertebrate hair cells.
Mechanotransduction in the auditory and vestibular systems depends on mechanosensitive ion channels in the stereociliary bundles that project from the apical surface of the sensory hair cells. In lower vertebrates, when the mechanoelectrical transducer (MET) channels are opened by movement of the bundle in the excitatory direction, Ca ²⁺ entry through the open MET channels causes adaptation, rapidly reducing their open probability and resetting their operating range. It remains uncertain whether such Ca ²⁺-dependent adaptation is also present in mammalian hair cells. Hair bundles of both outer and inner hair cells from mice were deflected by using sinewave or step mechanical stimuli applied using a piezo-driven fluid jet. We found that when cochlear hair cells were depolarized near the Ca ²⁺ reversal potential or their hair bundles were exposed to the in vivo endolymphatic Ca ²⁺ concentration (40 µM), all manifestations of adaptation, including the rapid decline of the MET current and the reduction of the available resting MET current, were abolished. MET channel adaptation was also reduced or removed when the intracellular Ca ²⁺ buffer 1,2-Bis(2-aminophenoxy)ethane- N , N , N ′, N ′-tetraacetic acid (BAPTA) was increased from a concentration of 0.1 to 10 mM. The findings show that MET current adaptation in mouse auditory hair cells is modulated similarly by extracellular Ca ²⁺, intracellular Ca ²⁺ buffering, and membrane potential, by their common effect on intracellular free Ca ²⁺.
The development of asymmetric patterns along biologically relevant axes is a hallmark of many vertebrate organs or structures. One example is the sensory epithelium of the mammalian auditory system. ...Two distinct types of mechanosensory hair cells (inner and outer) and at least six types of associated supporting cells are precisely and asymmetrically arrayed along the radial (medial-lateral) axis of the cochlear spiral. Immunolabeling of developing cochleae indicates differential expression of Glycogen synthase kinase 3β (GSK3β) along the same axis. To determine whether GSK3β plays a role in specification of cell fates along the medial-lateral axis, GSK3 activity was blocked pharmacologically in cochlear explants. Results indicate significant changes in both the number of hair cells and in the specification of hair cell phenotypes. The overall number of inner hair cells increased as a result of both a shift in the medial boundary between sensory and non-sensory regions of the cochlea and a change in the specification of inner and outer hair cell phenotypes. Previous studies have inhibited GSK3 as a method to examine effects of canonical Wnt signaling. However, quantification of changes in Wnt pathway target genes in GSK3-inhibited cochleae, and treatment with more specific Wnt agonists, indicated that the Wnt pathway is not activated. Instead, expression of Bmp4 in a population of GSK3β-expressing cells was shown to be down-regulated. Finally, addition of BMP4 to GSK3-inhibited cochleae achieved a partial rescue of the hair cell phenotype. These results demonstrate a role for GSK3β in the specification of cellular identities along the medial-lateral axis of the cochlea and provide evidence for a positive role for GSK3β in the expression of Bmp4.
•The organ of Corti is asymmetrically patterned along its medial-to-lateral axis.•GSK3b is expressed in unique cell types in the developing organ of Corti.•Inhibition of GSK3 induces a shift in medial-lateral patterning of the organ of Corti.•Some of the effects of GSK3 are mediated through a decrease in expression of BMP4.•Some of the effects of GSK3 on cochlear development are not mediated through canonical Wnts
Liposomal honokiol isolated from the genus Magnolia has been found to have antiangiogenic, anti-inflammatory and antitumor properties. However, there has no report on its role in hair growth. Hair ...follicles are life-long cycled organelles that go through from anagen, catagen and telogen stages and are regulated by diverse signaling pathways, including Wnt/β-catenin, Notch, Epidermal growth factor (EGF) and Sonic hegehog (SHH). Wnt signals are essential for the initiation of hair follicle placode development and a new potential target of hair loss treatment. This study was designed to investigate the effect of liposomal honokiol (Lip-honokiol) on inducing hair anagen. We identified the hair grew out in advance in the shaving area of C57BL/6N mice after the treatment of liposomal honokiol (Lip-honokiol) by daily abdominal injection. We first demonstrated that Lip-Honokiol activated the Wnt3a/β-catenin pathway and downregulated the transforming growth factor-β1 (TGF-β1) to promote hair growth in mice via immunohistochemistry and immunofluorescence staining. These findings suggest that Lip-honokiol activated the Wnt/β-catenin pathway and accelerated the transfer from the telogen to anagen stage and finally promoted the hair growth.
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•The Lip-honokiol was associated with the transfer of hair follicles from telogen stage to anagen stage.•The Lip-honokiol accelerated the hair growth cycle by upregulating the Wnt3a/β-catenin signaling pathway.•The Lip-honokiol inhibited the TGF-β1/p-smad2 signaling pathway during the anagen stage.•The Lip-honokiol increased the Ki67 and p-histone H3 expression by IHC.
The human keratin family comprises 54 members, 28 type I and 26 type II. Out of the 28 type I keratins, 17 are epithelial and 11 are hair keratins. Similarly, the 26 type II members comprise 20 ...epithelial and 6 hair keratins. As, however, 9 out of the 37 epithelial keratins are specifically expressed in the hair follicle, the total number of hair follicle-specific keratins (26) almost equals that of those expressed in the various forms of epithelia (28). Up to now, more than half of the latter have been found to be involved in inherited diseases, with mutated type I and type II members being roughly equally causal. In contrast, out of the 26 hair follicle-specific keratins only 5 have, at present, been associated with inherited hair disorders, while one keratin merely acts as a risk factor. In addition, all hair follicle-specific keratins involved in pathologies are type II keratins. Here we provide a detailed description of the respective hair diseases which are either due to mutations in hair keratins (monilethrix, ectodermal dysplasia of hair and nail type) or hair follicle-specific epithelial keratins (two mouse models, RCO3 and
Ca
Rin
as well as pseudofolliculitis barbae).
Minoxidil was first introduced as an antihypertensive medication and the discovery of its common adverse event, hypertrichosis, led to the development of a topical formulation for promoting hair ...growth. To date, topical minoxidil is the mainstay treatment for androgenetic alopecia and is used as an off-label treatment for other hair loss conditions. Despite its widespread application, the exact mechanism of action of minoxidil is still not fully understood. In this article, we aim to review and update current information on the pharmacology, mechanism of action, clinical efficacy, and adverse events of topical minoxidil.
Histopathology of aging of the hair follicle Fernandez‐Flores, Angel; Saeb‐Lima, Marcela; Cassarino, David S.
Journal of cutaneous pathology,
July 2019, 2019-Jul, 2019-07-00, 20190701, Letnik:
46, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Hair follicles experience several changes with aging, the most noticeable of which is graying of the hair shaft due to loss of melanin. Additional changes in the diameter and length of the hair have ...contributed to the concept of senescent alopecia, which is different from androgenetic alopecia according to most. Graying happens in most individuals, although in different grades and starting at different ages. It is related to a decrease in the number and activity of the melanocytes of the hair bulb, which eventually completely disappear from the bulb of the white hair. Residual non‐active melanocytes remain in the outer root sheath and in the bulge, which allows for repigmentation of the hair under certain stimuli or conditions.
Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study ...focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through a high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% whale oil) were topically applied to the dorsal skin of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained dorsal skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptome analysis also confirmed increases for 20% WO in filaggrin (
), a gene related to skin barrier function; fibroblast growth factor 21 (
), which is involved in hair follicle development; and cysteine-rich secretory protein 1 (
), a candidate gene for alopecia areata. Furthermore, the results of KEGG pathway analysis indicated that 20% WO may have lower stress and inflammatory responses than 3% MXD. Therefore, WO is expected to be a safe hair growth agent.
Mechanosensitive sensory hair cells are the linchpin of our senses of hearing and balance. The inability of the mammalian inner ear to regenerate lost hair cells is the major reason for the ...permanence of hearing loss and certain balance disorders. Here, we present a stepwise guidance protocol starting with mouse embryonic stem and induced pluripotent stem cells, which were directed toward becoming ectoderm capable of responding to otic-inducing growth factors. The resulting otic progenitor cells were subjected to varying differentiation conditions, one of which promoted the organization of the cells into epithelial clusters displaying hair cell-like cells with stereociliary bundles. Bundle-bearing cells in these clusters responded to mechanical stimulation with currents that were reminiscent of immature hair cell transduction currents.
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► ESCs and iPSCs can be guided along the otic lineage ► In vitro-differentiated cells display typical hair cell cytomorphology ► Mechanical responses are reminiscent of hair cell transduction currents
Objectives: A retrospective case-series study comparing autologous activated platelet-rich plasma (AA-PRP) versus autologous non-activated platelet-rich plasma (A-PRP) in hair re-growth was reported.
...Methods: 90 patients, 63 males showing AGA in stage I-V by the Norwood-Hamilton scale and 27 females with AGA in stage I-III by the Ludwig scale, treated since 2013, were analyzed. 57 patients were treated with A-PRP injections and 33 patients were treated with AA-PRP in three sessions spaced 30 days average. Assessment of hair re-growth was evaluated in different weeks (Ws) after the treatment, summarized in four phases: T0, before the first infusion, T1 - 12 Ws, T2 - 23 Ws, T3 - 44 Ws, T4 - 58 Ws after the last treatment.
Results: 12 Ws, 23 Ws, 44 Ws, and 58Ws after the last treatment, hair density measurements for patients treated with A-PRP and AA-PRP were 65 ± 5 and 28 ± 4 hairs/cm2 at T1, 28 ± 2 and 15 ± 3 hairs/cm2 at T2, 25 ± 3 and 14 ± 3 hairs/cm2 at T3, 23 ± 3 and 13 ± 3 hairs/cm
2
at T4.
Conclusion: The effects of A-PRP and AA-PRP in hair re-growth during a long-term follow-up, was demonstrated.
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