Mesothelial cell differentiation into osteoblast- and adipocyte-like cells.
Serosal pathologies including malignant mesothelioma (MM) can show features of osseous and/or cartilaginous differentiation although the mechanism for its formation is unknown. Mesothelial cells have the capacity to differentiate into cells with myofibroblast, smooth muscle and endothelial cell characteristics. Whether they can differentiate into other cell types is unclear. This study tests the hypothesis that mesothelial cells can differentiate into cell lineages of the embryonic mesoderm including osteoblasts and adipocytes. To examine this, a functional assay of bone formation and an adipogenic assay were performed in vitro with primary rat and human mesothelial cells maintained in osteogenic or adipogenic medium (AM) for 0-26 days. Mesothelial cells expressed increasing levels of alkaline phosphatase, an early marker of the osteoblast phenotype, and formed mineralized bone-like nodules. Mesothelial cells also accumulated lipid indicative of a mature adipocyte phenotype when cultured in AM. All cells expressed several key osteoblast and adipocyte markers, including osteoblast-specific runt-related transcription factor 2, and demonstrated changes in mRNA expression consistent with epithelial-to-mesenchymal transition. In conclusion, these studies confirm that mesothelial cells have the capacity to differentiate into osteoblast- and adipocyte-like cells, providing definitive evidence of their multipotential nature. These data strongly support mesothelial cell differentiation as the potential source of different tissue types in MM tumours and other serosal pathologies, and add support for the use of mesothelial cells in regenerative therapies.
Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, WA, Australia.
Sally M
SM
Lansley
Richelle G
RG
Searles
Aina
A
Hoi
Carla
C
Thomas
Helena
H
Moneta
Sarah E
SE
Herrick
Philip J
PJ
Thompson
Mark
M
Newman
Gregory F
GF
Sterrett
Cecilia M
CM
Prêle
Steven E
SE
Mutsaers
D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000254:growth & development*; D015870:Gene Expression; D006801:Humans; D050356:Lipid Metabolism; D008648:Mesoderm / Q000166:cytology* / Q000196:embryology; D008654:Mesothelioma / Q000378:metabolism*; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000235:genetics; D051381:Rats; D000951:Antigens, Neoplasm
D000469:Alkaline Phosphatase; D014408:Biomarkers, Tumor; D050659:Core Binding Factor Alpha 1 Subunit; C432845:HBME-1 antigen; D000951:Antigens, Neoplasm; C493709:RUNX2 protein, human