The balance of Bmp6 and Wnt10b regulates the telogen-anagen transition of hair follicles

Abstract

Background 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. Methods The 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. Results BMP6 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. Conclusions Combined 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. Electronic supplementary material The online version of this article (10.1186/s12964-019-0330-x) contains supplementary material, which is available to authorized users.

Twist1 Contributes to the Maintenance of Some Biological Properties of Dermal Papilla Cells in vitro by Forming a Complex With Tcf4 and β-Catenin

“…(Ben Amitai et al, 2006). VEGF is a vascular endothelial factor that can promote hair growth by inducing capillary formation around hair follicles (Zhang et al, 2019). Consistent with these results, Tcf4 and Twist1 increased the mRNA and protein levels of c-myc, survivin, and cyclin-D1 and the secretion of HGF, VEGF, and IGF-1 (Figures 2, 3).…”

Characterization of Embryonic Skin Transcriptome in Anser cygnoides at Three Feather Follicles Developmental Stages

“…Bone morphogenetic proteins (BMPs) belonging to the TGF-beta superfamily are dominant for skin development by regulating the proliferation, differentiation, and apoptosis of the keratinocyte, and are expressed in both epithelium and dermis (Lewis et al 2014). BMP6 (bone morphogenetic protein 6), with high expression level in the early anagen of hair follicles, has already been reported to have an inhibitory effect on hair follicle regeneration and telogen-anagen transition (Clavel et al 2012;Wu et al 2019). According to McDonnell et al (2001), keratinocytes that were treated with BMP6 induced the differentiation markers at the early stage instead of the later stage.…”

Targeting Wnt/β-Catenin Pathway for Developing Therapies for Hair Loss

“…Factors that regulate Wnt-β-catenin signaling in HF include androgen [ 51 ], BMP [ 52 ], soluble frizzled receptor protein-1 (sFRP1), and growth factors [ 53 , 54 , 55 ]. For example, treatment with dihydrotestosterone attenuated Wnt3a-induced TCF/Lef reporter activity in DP cells derived from androgenic alopecia [ 51 ].…”

“…While overexpression of BMP6 inhibited the expression of Wnt10b in HFSC, adenoviral Wnt10b treatment in telogenic HF reduced the number of BMP6-positive cells as compared to control. Since Wnt10b acts as an activator and BMP6 functions as an inhibitor of β-catenin signaling, a cellular balance between these opposing factors are required to regulate the telogen to anagen transition of hair follicles [ 52 ]. EGF treatment increased the nuclear translocation of β-catenin, and induced the expression of Wnt10b, β-catenin, EGF receptor, SOX9, and that of a number of follicle-regulatory genes, such as survivin, Msx2, and SGK3.…”