Ren Yi, Miao Xiaojing, Jiang Hui, Li Angze, Huo Longfei, Zhang Xuran, Fu Qiqi, Yang Jiali, Tian Jing, Liu Muqing
School of Information Science and Technology, Fudan University, 2005 Songhu Road, Shanghai 200438, China.
Academy for Engineering and Technology, Fudan University, 220 Handan Road, Shanghai 200433, China.
J Photochem Photobiol B. 2025 Sep;270:113210. doi: 10.1016/j.jphotobiol.2025.113210. Epub 2025 Jul 2.
Current therapeutic interventions for androgenetic alopecia (AGA) are hindered by limited efficacy and adverse side effects. Photobiomodulation (PBM) has emerged as a promising non-invasive alternative, demonstrating preliminary potential for hair follicle stimulation. However, its precise therapeutic mechanisms and optimal treatment parameters require systematic investigation. In the present study, we established an in vitro AGA model using dihydrotestosterone (DHT)-treated human dermal papilla cells (DPCs, 0-100 μM) to evaluate PBM efficacy across continuous wave (CW) and pulsed wave (PW) modes, enabling mechanistic and therapeutic assessment. Key findings revealed that the impact of PBM was highly sensitive to DHT concentration. At lower concentrations of DHT (0-50 μM), PBM therapy successfully improved mitochondrial function, reduced apoptosis, increased alkaline phosphatase activity, stimulated lactate dehydrogenase release, and boosted cell migration. These beneficial effects were particularly notable under 8 J/cm and 8 mW/cm (CW mode), as well as 8 J/cm, 10 mW/cm (peak irradiance), 500 Hz, and 80 % duty cycle under PW mode. However, these protective effects were substantially attenuated at higher DHT concentrations (100 μM). Mechanistically, PW PBM exerted dual anti-apoptotic and anti-androgenic effects through multi-pathway modulation: It activated the Wnt/β-catenin pathway while concurrently suppressing BMP and TGF-β signaling cascades. This investigation elucidates the molecular mechanisms by which PBM inhibits DHT-induced apoptosis in DPCs. Furthermore, it demonstrates that the therapeutic efficacy of PBM is significantly mitigated under hyperandrogenic conditions. Overall, our findings provide critical insights for optimizing light-based therapeutic strategies and advancing clinical translation of PBM for AGA management.
目前雄激素性脱发（AGA）的治疗干预因疗效有限和不良副作用而受到阻碍。光生物调节（PBM）已成为一种有前景的非侵入性替代方法，显示出刺激毛囊的初步潜力。然而，其确切的治疗机制和最佳治疗参数需要系统研究。在本研究中，我们使用二氢睾酮（DHT）处理的人真皮乳头细胞（DPCs，0 - 100 μM）建立了体外AGA模型，以评估连续波（CW）和脉冲波（PW）模式下的PBM疗效，从而进行机制和治疗评估。主要研究结果表明，PBM的影响对DHT浓度高度敏感。在较低的DHT浓度（0 - 50 μM）下，PBM疗法成功改善了线粒体功能，减少了细胞凋亡，增加了碱性磷酸酶活性，刺激了乳酸脱氢酶释放，并促进了细胞迁移。这些有益效果在8 J/cm²和8 mW/cm²（CW模式）以及PW模式下的8 J/cm²、10 mW/cm²（峰值辐照度）、500 Hz和80%占空比下尤为显著。然而，在较高的DHT浓度（100 μM）下，这些保护作用显著减弱。从机制上讲，PW PBM通过多途径调节发挥双重抗凋亡和抗雄激素作用：它激活Wnt/β-连环蛋白通路，同时抑制BMP和TGF-β信号级联反应。本研究阐明了PBM抑制DPCs中DHT诱导的细胞凋亡的分子机制。此外，研究表明在高雄激素条件下PBM的治疗效果显著降低。总体而言，我们的研究结果为优化基于光的治疗策略和推进PBM用于AGA治疗的临床转化提供了关键见解。
