L-Carnitine-L-tartrate promotes human hair growth in vitro

Abstract: The trimethylated amino acid l-carnitine plays a key role in the intramitochondrial transport of fatty acids for b-oxidation and thus serves important functions in energy metabolism. Here, we have tested the hypothesis that l-carnitine, a frequently employed dietary supplement, may also stimulate hair growth by increasing energy supply to the massively proliferating and energy-consuming anagen hair matrix. Hair follicles (HFs) in the anagen VI stage of the hair cycle were cultured in the presence of 0.5-50 lm of l-carnitine-l-tartrate (CT) for 9 days. At day 9, HFs treated with 5 lm or 0.5 lm of CT showed a moderate, but significant stimulation of hair shaft elongation compared with vehicletreated controls (P < 0.05). Also, CT prolonged the duration of anagen VI, down regulated apoptosis (as measured by TUNEL assay) and up regulated proliferation (as measured by Ki67 immunohistology) of hair matrix keratinocytes (P < 0.5). By immunohistology, intrafollicular immunoreactivity for TGFb2, a key catagen-promoting growth factor, in the dermal papilla and TGF-b II receptor protein in the outer root sheath and dermal papilla was down regulated. As shown by caspase activity assay, caspase 3 and 7, which are known to initiate apoptosis, are down regulated at day 2 and day 4 after treatment of HFs with CT compared with vehicle-treated control indicating that CT has an immediate protective effect on HFs to undergo programmed cell death. Our findings suggest that l-carnitine stimulates human scalp hair growth by up regulation of proliferation and down regulation of apoptosis in follicular keratinocytes in vitro. They further encourage one to explore topical and nutraceutical administration of l-carnitine as a well-tolerated, relatively safe adjuvant treatment in the management of androgenetic alopecia and other forms of hair loss

LCarnitine-L-tartrate promotes human hair growth in vitro

Abstract: The trimethylated amino acid l-carnitine plays a key role in the intramitochondrial transport of fatty acids for b-oxidation and thus serves important functions in energy metabolism. Here, we have tested the hypothesis that l-carnitine, a frequently employed dietary supplement, may also stimulate hair growth by increasing energy supply to the massively proliferating and energy-consuming anagen hair matrix. Hair follicles (HFs) in the anagen VI stage of the hair cycle were cultured in the presence of 0.5-50 lm of l-carnitine-l-tartrate (CT) for 9 days. At day 9, HFs treated with 5 lm or 0.5 lm of CT showed a moderate, but significant stimulation of hair shaft elongation compared with vehicletreated controls (P < 0.05). Also, CT prolonged the duration of anagen VI, down regulated apoptosis (as measured by TUNEL assay) and up regulated proliferation (as measured by Ki67 immunohistology) of hair matrix keratinocytes (P < 0.5). By immunohistology, intrafollicular immunoreactivity for TGFb2, a key catagen-promoting growth factor, in the dermal papilla and TGF-b II receptor protein in the outer root sheath and dermal papilla was down regulated. As shown by caspase activity assay, caspase 3 and 7, which are known to initiate apoptosis, are down regulated at day 2 and day 4 after treatment of HFs with CT compared with vehicle-treated control indicating that CT has an immediate protective effect on HFs to undergo programmed cell death. Our findings suggest that l-carnitine stimulates human scalp hair growth by up regulation of proliferation and down regulation of apoptosis in follicular keratinocytes in vitro. They further encourage one to explore topical and nutraceutical administration of l-carnitine as a well-tolerated, relatively safe adjuvant treatment in the management of androgenetic alopecia and other forms of hair loss

The TGF-β2 Isoform Is Both a Required and Sufficient Inducer of Murine Hair Follicle Morphogenesis

Hair follicle development serves as an excellent model to study control of organ morphogenesis. Three specific isoforms of TGF-β exist which exhibit a distinct pattern of expression during hair follicle morphogenesis. To clarify the still elusive role of these factors in hair follicle development, we have used a combined genetic and functional approach: analysis of hair follicle development in mice with disruptions of the TGF-β1, 2, and 3 genes was coupled with a direct functional test of the effect of added purified factors on fetal hair follicle development in skin organ cultures. TGF-β2 null mice exhibited a profound delay of hair follicle morphogenesis, with a 50% reduced number of hair follicles. In contrast to hair follicle development, growth and differentiation of interfollicular keratinocytes proceeded unimpaired. Unlike TGF-β2−/− mice, mice with a disruption of the TGF-β1 gene showed slightly advanced hair follicle formation, while lack of the TGF-β3 gene did not have any effects. Treatment of wild-type, embryonic skin explants (E14.5 or E15.5) with TGF-β2 protein in either soluble form or slow release beads induced hair follicle development and epidermal hyperplasia, while similar TGF-β1 treatment exerted suppressive effects. Thus, the TGF-β2 isoform plays a specific role, not shared by the other TGF-β isoforms, as an inducer of hair follicle morphogenesis and is both required and sufficient to promote this process

Towards Dissecting the Pathogenesis of Retinoid-Induced Hair Loss: All-Trans Retinoic Acid Induces Premature Hair Follicle Regression (Catagen) by Upregulation of Transforming Growth Factor-β2 in the Dermal Papilla

Diffuse hair loss ranks among the most frequent and psychologically most distressing adverse effects of systemic therapy with retinoids, which severely limits their therapeutic use even where clinically desired. Since the underlying mechanisms of retinoid-induced effluvium are as yet unknown, we have investigated the influence of the prototypic retinoid all-trans retinoic acid (ATRA, tretinoin) on the growth of human scalp hair follicles (HF) in culture. HF in the anagen VI stage of the hair cycle were cultured in the presence of 10−8 or 10−10 M ATRA. Compared with controls, hair shaft elongation declined significantly already after 2 d in the ATRA-treated group, and approximately 80% of the ATRA-treated HF had prematurely entered catagen-like stage at day 6, compared with 30% in the control group. This corresponded to an upregulation of apoptotic and a downregulation of Ki67-positive cells in ATRA-treated HF. Since transforming growth factor (TGF)-β has been implicated as a key inducer of catagen, we next studied whether ATRA treatment had any effect on follicular expression. TGF-β2 immunoreactivity was detected in the outer root sheath of anagen VI scalp HF. In catagen follicles, TGF-β2 was also expressed in the regressing epithelial strand. After 4 d of ATRA treatment, TGF-β2 was significantly upregulated in anagen HF in the dermal papilla (DP) and the dermal sheath, 7, and TGF-β neutralizing antibody partially abrogated at RA induced hair growth inhibition. Real-time PCR confirmed a significant upregulation of TGF-β2 transcripts in ATRA-treated hair bulbs. This study is the first to provide direct evidence that ATRA can indeed induce a catagen-like stage in human HF and suggests that this occurs, at least in part, via upregulation of TGF-β2 in the DP. Therefore, topical TGF-β2/TGF-β receptor II antagonists deserve to be explored for the prevention and management of retinoid-induced hair loss

Mast cells are required for normal healing of skin wounds in mice.

Mast cells (MCs) have recently been reported to play a pivotal role in the elicitation of inflammatory reactions that are beneficial to the host, e.g., during innate immune responses to bacteria. To explore whether MCs also contribute to wound repair, we studied experimentally induced skin wounds in MC‐deficient KitW/KitW‐v mice, normal Kit/ mice, and MC‐reconstituted KitW/KitW‐v mice. Wound closure was significantly impaired in the absence of MCs during the first 6 days of wound healing and histomorphometric analyses of MC degranulation at the wound edges revealed distance‐dependent MC activation, i.e., MC degranulation was most prominent directly adjacent to the wound. In addition, KitW/KitW‐v mice showed impaired extravasation and recruitment of neutrophils to the wounded areas. Notably, wound closure, extravasation, and neutrophil recruitment were found to be normal in MC‐reconstituted KitW/KitW‐v mice. Therefore, we examined whether MCs promote wound healing by releasing histamine or TNF‐. Interestingly, wound closure was reduced in mice treated with an H1‐receptor antagonist but not after treatment with an H2‐receptor antagonist or in the absence of TNF‐. Taken together, our findings indicate that MC activation and histamine release are required for normal cutaneous wound healing.—Weller, K., Foitzik, K., Paus, R., Syska, W., Maurer, M. Mast cells are required for normal healing of skin wounds in mice. FASEB J. 20, E1628 –E1635 (2006

Burden of Hair Loss: Stress and the Underestimated Psychosocial Impact of Telogen Effluvium and Androgenetic Alopecia

Hair loss, as it occurs with telogen effluvium and androgenetic alopecia, provokes anxieties and distress more profound than its objective severity would appear to justify. This reflects the profound symbolic and psychosocial importance of hair. Stress has long been implicated as one of the causal factors involved in hair loss. Recently, in vivo studies in mice have substantiated the long-held popular belief that stress can exert profound hair growth-inhibitory catagen-inducing and hair-damaging pro-inflammatory effects. Insights into the negative impact of stress on hair growth and the integration of stress-coping strategies into the management of hair loss disorders as well as the development of new pharmacotherapeutic strategies might lead to enhanced therapeutic modalities with the alleviation of clinical symptoms as well as the concomitant psychological implications