Alam M, Bertolini M, Gherardini J, Keren A, Ponce L, Chéret J, Alenfall J, Dunér P, Nilsson A H, Gilhar A, Paus R
Monasterium Laboratory - Skin and Hair Research Solutions GmbH, Münster, Germany.
Mediteknia Skin & Hair Lab, Las Palmas de Gran Canaria, Spain.
Br J Dermatol. 2020 Jun;182(6):1404-1414. doi: 10.1111/bjd.18479. Epub 2019 Nov 1.
Given that unwanted hair growth (hirsutism, hypertrichosis) can cause major psychological distress, new pharmacological treatment strategies with safe and effective hair growth inhibitors that do not destroy the hair follicle (HF) and its stem cells need to be developed.
To establish if osteopontin-derived fragments may modulate human hair growth given that human HFs express the multifunctional, immunomodulatory glycoprotein, osteopontin.
Our hypothesis was tested ex vivo and in vivo by using a newly generated, toxicologically well-characterized, modified osteopontin-derived peptide (FOL-005), which binds to the HF.
In organ-cultured human HFs and scalp skin, and in human scalp skin xenotransplants onto SCID mice, FOL-005 treatment (60 nmol L to 3 μmol L ) significantly promoted premature catagen development without reducing the number of keratin 15-positive HF stem cells or showing signs of drug toxicity. Genome-wide DNA microarray, quantitative reverse-transcriptase polymerase chain reaction and immunohistochemistry revealed decreased expression of the hair growth promoter, fibroblast growth factor-7 (FGF7) by FOL-005, while cotreatment of HFs with recombinant FGF7 partially abrogated FOL-005-induced catagen promotion.
With caveats in mind, our study identifies this osteopontin-derived peptide as an effective, novel inhibitory principle for human hair growth ex vivo and in vivo, which deserves systematic clinical testing in hirsutism and hypertrichosis. What's already known about this topic? The treatment of unwanted hair growth (hypertrichosis, hirsutism) lacks pharmacological intervention, with only few and often unsatisfactory treatments available. Osteopontin is prominently expressed in human HFs and has been reported to be elevated during catagen in the murine hair cycle. What does this study add? We tested the effects on hair growth of a novel, osteopontin-derived fragment (FOL-005) ex vivo and in vivo. In human hair follicles, high-dose FOL-005 significantly reduces hair growth both ex vivo and in vivo. What is the translational message? High-dose FOL-005 may provide a new therapeutic opportunity as a treatment for unwanted hair growth.
鉴于毛发过度生长（多毛症、毛发增多症）会引起严重的心理困扰，需要研发新的药理学治疗策略，使用安全有效的毛发生长抑制剂，且不破坏毛囊（HF）及其干细胞。
鉴于人类毛囊表达多功能免疫调节糖蛋白骨桥蛋白，确定骨桥蛋白衍生片段是否可调节人类毛发生长。
通过使用新生成的、毒理学特征明确的、修饰的骨桥蛋白衍生肽（FOL-005）进行体外和体内试验，验证我们的假设，该肽可与毛囊结合。
在器官培养的人类毛囊和头皮皮肤中，以及在移植到SCID小鼠身上的人类头皮皮肤异种移植模型中，FOL-005处理（60 nmol/L至3 μmol/L）显著促进了退行期提前发生，而未减少角蛋白15阳性毛囊干细胞数量，也未显示出药物毒性迹象。全基因组DNA微阵列、定量逆转录聚合酶链反应和免疫组织化学显示，FOL-005使毛发生长促进因子成纤维细胞生长因子-7（FGF7）的表达降低，而用重组FGF7对毛囊进行共处理可部分消除FOL-005诱导的退行期促进作用。
考虑到一些注意事项，我们的研究确定这种骨桥蛋白衍生肽在体外和体内都是一种有效的、新型的人类毛发生长抑制因子，值得在多毛症和毛发增多症中进行系统的临床试验。关于该主题已知的信息有哪些？毛发过度生长（毛发增多症、多毛症）的治疗缺乏药理学干预，可用治疗方法很少且往往不尽人意。骨桥蛋白在人类毛囊中大量表达，据报道在小鼠毛发周期的退行期会升高。本研究增加了什么内容？我们在体外和体内测试了一种新型骨桥蛋白衍生片段（FOL-005）对毛发生长的影响。在人类毛囊中，高剂量FOL-005在体外和体内均显著减少毛发生长。该研究的转化意义是什么？高剂量FOL-005可能为毛发过度生长的治疗提供新的治疗机会。
