Mesothelial cell differentiation into osteoblast- and adipocyte-like cells

Our plain-English summary of Mesothelial cell differentiation into osteoblast- and adipocyte-like cells, by S.M. Lansley, R.G. Searles, A. Hoi, et al (Journal of Cellular and Molecular Medicine, 2011).

The study

• Authors: S.M. Lansley, R.G. Searles, A. Hoi, C. Thomas, H. Moneta, S.E. Herrick, P.J. Thompson, M. Newman, G.F. Sterrett, C.M. Prêle, S.E. Mutsaers
• Journal: Journal of Cellular and Molecular Medicine
• Published: 2011;15(10):2095-105
• Cited by: 58 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

In plain English

This laboratory study tested whether mesothelial cells can become bone-forming (osteoblast-like) and fat (adipocyte-like) cells. It did not study asbestos. The authors examined one patient's pleural malignant mesothelioma biopsy and found multiple areas of bone-like tissue, with mineralized bone, inside the tumour. They grew mesothelial cells from young male rats and from heart-sac fluid of nine adult heart-surgery patients in special media for up to 26 days. Rat cells formed nodules that showed mineralization by day 18. In rat cells, messenger RNA for RUNX2, a bone-cell gene, rose overall, though RUNX2 protein appeared to decrease. Rat cells also showed gene changes consistent with epithelial-to-mesenchymal transition. Of three human cultures, two lacked alkaline phosphatase staining, a bone-cell marker, and no mineralized nodules were detected in any sample. Rat cells built up fat significantly by day 18, while very few human cells did. The authors concluded that mesothelial cells can differentiate into osteoblasts and adipocytes, which they said provides a mechanism for bone in mesothelioma tumours. They noted the biopsy was too small to judge how often bone occurs in these tumours.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture experiments with rat and human mesothelial cells, plus examination of one human pleural mesothelioma biopsy
• Who was studied: Mesothelial cells from 6–8 week old male Lewis rats, and from pericardial fluid of nine adult patients (median age 65, range 57–81) undergoing coronary artery bypass surgery, Western Australia; also one biopsy from a patient with pleural malignant mesothelioma
• Exposure: No asbestos or fiber exposure was studied. Cells were grown in osteogenic (bone-promoting) medium for 0–26 days or adipogenic (fat-promoting) medium for up to 18 days, compared with standard medium.
• Main results:
  • In the single human pleural mesothelioma biopsy, multiple areas of osseous metaplasia (bone-like tissue) were seen with mineralized bone
  • Rat mesothelial cells in osteogenic medium formed nodule-like structures that showed mineralization by day 18
  • In rat mesothelial cells, RUNX2 mRNA increased overall over time in culture, but RUNX2 protein appeared to decrease
  • In rat mesothelial cells, mRNA for markers linked to epithelial-to-mesenchymal transition (SMA, s100A4, MMP28, SNAI1) was absent or very low at day 0 and present by day 5
  • Human mesothelial cells: alkaline phosphatase staining was absent in two of three cultures, and no mineralized nodules were detected in any of the samples
  • Rat mesothelial cells in adipogenic medium accumulated lipid from day 6, increasing significantly by day 18
  • Very few human mesothelial cells accumulated lipid, although they expressed mRNA for adipocyte markers after exposure to adipogenic medium
• The authors' conclusion: The authors concluded that they had strong evidence that mesothelial cells can differentiate into osteoblasts and adipocytes, and that this provides a mechanism by which bone forms in malignant mesothelioma tumours
• Limitations the authors state:
  • How often bone occurs in mesothelioma tumours, and how much, could not be determined because the biopsy tissue sample was small
  • The RUNX2 antibody used for protein measurement did not recognize only the bone-specific form of RUNX2
  • The authors did not test whether the cell changes were reversible
  • Whether mesothelium is similar regardless of body site or species still needs investigation

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Malignant Mesothelioma, Mesoderm.

Related studies

• A Subset of Malignant Mesothelioma Tumors Retain Osteogenic Potential — S.M. Lansley, B. Pedersen, et al. (2016)
• Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production — S.H. Chew, Y. Okazaki, et al. (2014)
• A new insight into the histogenesis of 'mesodermomas'--malignant mesotheliomas — A. Donna, P.G. Betta, et al. (1991)
• Poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/fibrinogen/bredigite nanofibrous membranes and their integration with osteoblasts for guided bone regeneration — M. Kouhi, V. Jayarama Reddy, et al. (2019)
• Stimulatory effects of the ionic products from Ca-Mg-Si bioceramics on both osteogenesis and angiogenesis in vitro — W. Zhai, H. Lu, et al. (2013)
• Strain differences in pleural mesothelial cell reactions induced by potassium octatitanate fibers (TISMO) infused directly into the thoracic cavity — M. Yokohira, Y. Nakano, et al. (2013)

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