Abstract

BackgroundThe periodic growth of hair follicles is regulated by the balance of activators and inhibitors. The BMP signaling pathway plays an important role during hair follicle regeneration, but the exact BMP protein that controls this process has not been revealed.MethodsThe expression of BMP6 was determined via in situ hybridization and immunofluorescence. The in vivo effect of BMP6 overexpression was studied by using a previously established adenovirus injection model. The hair follicle regeneration was assessed by gross observation, H&E staining and 5-bromo-2-deoxyuridine (BrdU) tracing. The expression patterns of BMP6 signaling and Wnt10b signaling in both AdBMP6-treated and AdWnt10b-treated skins were determined by in situ hybridization and immunofluorescence.ResultsBMP6 was expressed differently in the stages of hair follicle cycle. The telogen-anagen transition of hair follicles was inhibited by adenovirus-mediated overexpression of BMP6. In the in vivo model, the BMP6 signaling was inhibited by Wnt10b and the Wnt10b signaling was inhibited by BMP6. The activation of hair follicle stem cells (HFSCs) was also competitively regulated by Wnt10b and BMP6.ConclusionsCombined with previously reported data of Wnt10b, our findings indicate that BMP6 and Wnt10b are major inhibitors and activators respectively and their balance regulates the telogen-anagen transition of hair follicles. To the best of our knowledge, our data provide previously unreported insights into the regulation of hair follicle cycling and provide new clues for the diagnosis and therapies of hair loss.

Highlights

  • The periodic growth of hair follicles is regulated by the balance of activators and inhibitors

  • BMP6 inhibits the telogen-anagen transition in vivo To determine the role of BMP6 in the hair cycle, we introduced a synchronization model of hair follicles and injected Adenovirus with bone morphogenetic protein 6 (AdBMP6) intradermally into the skin of synchronized C57 mice

  • BMP6 inhibits the proliferation of hair follicle stem cells (HFSCs) Previously, we reported that overexpression of Wnt10b activated HFSCs in vivo [11]

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Summary

Introduction

The periodic growth of hair follicles is regulated by the balance of activators and inhibitors. The BMP signaling pathway plays an important role during hair follicle regeneration, but the exact BMP protein that controls this process has not been revealed. The hair follicle is a specific mini-organ with the ability to undergo periodic growth and is an effective model for tissue regeneration research. Research on the regulation of the hair follicle cycle is focused on anagen onset. Previous reports showed that in late telogen, the balance between activators and inhibitors may determine whether a hair follicle can reenter anagen [1,2,3]. Activators and inhibitors may be of intrafollicular or extrafollicular origin [4] Many signaling pathways, such as the Wnt

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