Bone morphogenetic proteins differentially regulate pigmentation in human skin cells
Publication date
2012Keyword
AdultAged
Bone Morphogenetic Protein 4; Antagonists & inhibitors; Metabolism; Pharmacology
Bone Morphogenetic Protein 6; Antagonists & inhibitors; Metabolism; Pharmacology
Bone Morphogenetic Protein Receptors
Coculture techniques
Epidermis; Drug effects; Radiation effects
Female
Gene knockdown techniques
Humans
Keratinocytes; Enzymology
Melanins; Biosynthesis
Melanocytes; Ultrastructure
Middle aged
Models; Biological
Monophenol Monooxygenase
Myosins
Pigmentation
Pseudopodia
Signal transduction
Skin; cytology
Smad Proteins
Ultraviolet rays
Up-Regulation
p38 Mitogen-Activated Protein Kinases
REF 2014
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Show full item recordAbstract
Bone morphogenetic proteins (BMPs) are a large family of multi-functional secreted signalling molecules. Previously BMP2/4 were shown to inhibit skin pigmentation by downregulating tyrosinase expression and activity in epidermal melanocytes. However, a possible role for other BMP family members and their antagonists in melanogenesis has not yet been explored. In this study we show that BMP4 and BMP6, from two different BMP subclasses, and their antagonists noggin and sclerostin were variably expressed in melanocytes and keratinocytes in human skin. We further examined their involvement in melanogenesis and melanin transfer using fully matched primary cultures of adult human melanocytes and keratinocytes. BMP6 markedly stimulated melanogenesis by upregulating tyrosinase expression and activity, and also stimulated the formation of filopodia and Myosin-X expression in melanocytes, which was associated with increased melanosome transfer from melanocytes to keratinocytes. BMP4, by contrast, inhibited melanin synthesis and transfer to below baseline levels. These findings were confirmed using siRNA knockdown of BMP receptors BMPR1A/1B or of Myosin-X, as well as by incubating cells with the antagonists noggin and sclerostin. While BMP6 was found to use the p38MAPK pathway to regulate melanogenesis in human melanocytes independently of the Smad pathway, p38MAPK, PI3-K and Smad pathways were all involved in BMP6-mediated melanin transfer. This suggests that pigment formation may be regulated independently of pigment transfer. These data reveal a complex involvement of regulation of different members of the BMP family, their antagonists and inhibitory Smads, in melanocytes behaviour.Citation
Singh, S. K., Abbas, W. A., Tobin, D. J. (2012) Bone morphogenetic proteins differentially regulate pigmentation in human skin cells. Journal of Cell Science, 125 (Pt 18), 4306-19.Link to publisher’s version
http://dx.doi.org/10.1242/jcs.102038Type
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