Background Androgenetic alopecia (AGA) is one of the most common types of hair loss in clinical practice, but the current clinical treatment options are limited and the efficacy of traditional drugs is unstable. Low-level laser therapy (LLLT) has been proven to have a clinical effect in promoting hair growth, but its mechanism of action remains unclear. In this study, a mouse model of hair loss induced by dihydrotestosterone was used, with hair follicle stem cells as the research target, to systematically explore the molecular biological mechanism of LLLT in promoting hair regeneration, providing a theoretical basis for clinical application.

Objective To investigate the efficacy and underlying mechanisms of low-level laser therapy (LLLT) in promoting hair regeneration in AGA mice.

Methods Sixty 7-week-old male C57BL/6J mice were randomly divided into blank, model, minoxidil, LLLT 20 min, and LLLT 30 min groups. Except for the blank group, all mice received intraperitoneal injections of dihydrotestosterone (DHT) for 4 days, followed by dorsal depilation and continued DHT administration to establish an AGA model. The blank and model groups were treated with distilled water, the minoxidil group received topical minoxidil, and the LLLT groups were treated with a 650 nm laser (5 mW/cm²) for 20 or 30 min daily for 4 weeks. Skin and hair samples were collected on days 7, 14, and 21 for morphological and histological evaluation, and transcriptomic analysis was performed on day 21 tissues. Data were analyzed using the t-test.

Results Compared with the model group, mice in the LLLT treatment groups showed significantly increased dorsal hair coverage and thicker hair shafts (P < 0.05), with greater improvement in the 30 min group than in the 20 min group. Hair morphology in the LLLT groups was comparable to that of the minoxidil group. HE staining revealed a significant increase in the number of hair follicles per unit area in LLLT-treated mice, with intact and well-organized hair bulb structures and densely arranged matrix cells. Ki67 fluorescence intensity was markedly enhanced (P < 0.05). Transcriptomic analysis indicated that LLLT exerted its therapeutic effects by modulating mitochondrial energy metabolism and upregulating key genes and protein expression in the Wnt/β-catenin and PI3K/Akt/mTOR signaling pathways, thereby activating hair follicle stem cells, promoting angiogenesis, and systematically enhancing hair regeneration.

Conclusion LLLT treatment activates the differentiation of hair follicle stem cells and promotes their proliferation, thereby inducing hair follicles to re-enter the anagen (growth) phase and exerting therapeutic effects.