Photobiomodulation mitigates DHT-induced apoptosis in dermal papilla cells via mitochondrial rescue and Wnt/TGF-β/BMP signaling modulation.

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/cm2 and 8 mW/cm2 (CW mode), as well as 8 J/cm2, 10 mW/cm2 (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.