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dc.contributor.authorSingh, Suman K.*
dc.contributor.authorAbbas, Waqas A.*
dc.contributor.authorTobin, Desmond J.*
dc.date.accessioned2014-04-28T11:21:22Z
dc.date.available2014-04-28T11:21:22Z
dc.date.issued2012
dc.identifier.citationSingh, 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.
dc.identifier.urihttp://hdl.handle.net/10454/6194
dc.description.abstractBone 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.
dc.relation.isreferencedbyhttp://dx.doi.org/10.1242/jcs.102038
dc.subjectAdult
dc.subjectAged
dc.subjectBone Morphogenetic Protein 4; Antagonists & inhibitors; Metabolism; Pharmacology
dc.subjectBone Morphogenetic Protein 6; Antagonists & inhibitors; Metabolism; Pharmacology
dc.subjectBone Morphogenetic Protein Receptors
dc.subjectCoculture techniques
dc.subjectEpidermis; Drug effects; Radiation effects
dc.subjectFemale
dc.subjectGene knockdown techniques
dc.subjectHumans
dc.subjectKeratinocytes; Enzymology
dc.subjectMelanins; Biosynthesis
dc.subjectMelanocytes; Ultrastructure
dc.subjectMiddle aged
dc.subjectModels; Biological
dc.subjectMonophenol Monooxygenase
dc.subjectMyosins
dc.subjectPigmentation
dc.subjectPseudopodia
dc.subjectSignal transduction
dc.subjectSkin; cytology
dc.subjectSmad Proteins
dc.subjectUltraviolet rays
dc.subjectUp-Regulation
dc.subjectp38 Mitogen-Activated Protein Kinases
dc.subjectREF 2014
dc.titleBone morphogenetic proteins differentially regulate pigmentation in human skin cells
dc.typeArticle


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