A biophysical approach to quantify skeletal stem cells trans-differentiation as a model for the study of osteoporosis

Biophys Chem. 2017 Oct:229:84-92. doi: 10.1016/j.bpc.2017.05.011. Epub 2017 May 26.

Abstract

The stroma of human bone marrow contains a population of skeletal stem cells (hBM-MSC) which are common ancestors, among the others, of osteoblasts and adipocytes. It has been proposed that the imbalance between hBM-MSC osteogenesis and adipogenesis, which naturally accompanies bone marrow senescence, may contribute to the development of bone-associated diseases, like osteoporosis. The possibility to reproduce this mechanism in vitro has been demonstrated, providing a good model to disclose the details of the complex bone-fat generation homeostasis. Nevertheless, the lack of a simple approach to quantitatively assess the actual stage of a cellular population hindered the adoption of this in vitro model. In this work, the direct differentiation of hBM-MSCs towards a single (osteo or adipo) lineage was characterized using quantitative biophysical and biological approaches, together with the parallel process of trans-differentiation from one lineage to the other. The results confirm that the original plasticity of hBM-MSCs is maintained along the initial stages of the differentiation, showing that in vitro conversion of pre-osteoblasts into adipocytes and, vice versa, of pre-adipocytes into osteoblasts is extremely efficient, comparable with the direct differentiation. Moreover, a method based on digital holography is proposed, providing a quantitative indication of the phenotype stage along differentiation.

Keywords: Adipocyte; Morphometry; Osteoblast; Quantitative phase imaging; Real time qPCR.

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Biophysical Phenomena
  • Bone Marrow Cells / cytology
  • Cell Differentiation
  • Cell Lineage
  • Cell Transdifferentiation*
  • Cells, Cultured
  • Fatty Acid-Binding Protein 7 / genetics
  • Fatty Acid-Binding Protein 7 / metabolism
  • Holography
  • Humans
  • Imaging, Three-Dimensional
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Microscopy, Phase-Contrast
  • Models, Biological*
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteoporosis / metabolism
  • Osteoporosis / physiopathology*
  • RNA / isolation & purification
  • RNA / metabolism
  • Real-Time Polymerase Chain Reaction
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • FABP7 protein, human
  • Fatty Acid-Binding Protein 7
  • Tumor Suppressor Proteins
  • Osteocalcin
  • RNA