P182 Role of bone morphogenetic protein-4 signalling and its natural inhibitors with narrowband ultraviolet B phototherapy in patients with nonsegmental vitiligo

Abstract

Nonsegmental vitiligo (NSV) demonstrates highly variable responses to narrowband ultraviolet B (NB-UVB) phototherapy, although it remains one of the most effective repigmentation therapies. The biological drivers of this heterogeneity are poorly defined. The bone morphogenetic protein (BMP) pathway – especially BMP-4, a known inhibitor of melanogenesis, and its antagonists noggin, gremlin and sclerostin – may influence melanocyte survival and pigment induction. This study evaluated BMP-4 signalling in vitro and in vivo to clarify its role in NB-UVB-induced repigmentation. We aimed to examine (i) how monobenzylether of hydroquinone (MBEH)-induced depigmentation affects BMP-4 signalling in melanocytes, and (ii) how NB-UVB therapy modulates BMP-4 and its antagonists in lesional vitiligo skin, and their correlation with melanogenesis gene expression. Normal human melanocytes (NHMs; three biological replicates per condition) were treated with graded MBEH doses (15–240 μmol L−1). Cell viability (MTT assay) and expression of melanogenesis genes (MITF, TYR, TYRP1 and DCT) and BMP-4 were quantified by reverse-transcriptase polymerase chain reaction (RT-PCR). For the in vivo arm, patients with NSV aged 18–60 years (n = 25) underwent whole-body NB-UVB thrice weekly using standard incremental dosing. Paired lesional biopsies were collected before and after phototherapy (25 RNA samples; 11 immunofluorescence samples). RT-PCR was used to quantify BMP-4, noggin, gremlin, sclerostin and melanogenesis markers. Immunofluorescence was used to assess protein expression changes. MTT assays identified 60 μmol L−1 (48 h) and 240 μmol L−1 (24 h) as the optimal depigmenting doses. These doses significantly reduced MITF and TYR expression (P < 0.01) and produced a marked increase in BMP-4, indicating activation of an antimelanogenic pathway in vitro. In vivo, 20 of 25 patients demonstrated clinical pigmentation improvement. These responders showed significant reductions in BMP-4 mRNA and a corresponding increase in gremlin after NB-UVB (P < 0.05). Immunofluorescence in paired samples (n = 11) confirmed reduced BMP-4 protein with enhanced basal-layer pigmentation. Successful NB-UVB-induced repigmentation is characterized by downregulation of BMP-4 and upregulation of gremlin, identifying this pathway as a promising biomarker and therapeutic target to optimize repigmentation outcomes in vitiligo.