Pleiotrophin commits human bone marrow mesenchymal stromal cells towards hypertrophy during chondrogenesis

PLoS One. 2014 Feb 7;9(2):e88287. doi: 10.1371/journal.pone.0088287. eCollection 2014.

Abstract

Pleiotrophin (PTN) is a growth factor present in the extracellular matrix of the growth plate during bone development and in the callus during bone healing. Bone healing is a complicated process that recapitulates endochondral bone development and involves many cell types. Among those cells, mesenchymal stromal cells (MSC) are able to differentiate toward chondrogenic and osteoblastic lineages. We aimed to determine PTN effects on differentiation properties of human bone marrow stromal cells (hBMSC) under chondrogenic induction using histological analysis and quantitative reverse transcription polymerase chain reaction. PTN dramatically potentiated chondrogenic differentiation as indicated by a strong increase of collagen 2 protein, and cartilage-related gene expression. Moreover, PTN increased transcription of hypertrophic chondrocyte markers such as MMP13, collagen 10 and alkaline phosphatase and enhanced calcification and the content of collagen 10 protein. These effects are dependent on PTN receptors signaling and PI3 K pathway activation. These data suggest a new role of PTN in bone regeneration as an inducer of hypertrophy during chondrogenic differentiation of hBMSC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Carrier Proteins / metabolism*
  • Cell Differentiation / physiology*
  • Cell Enlargement*
  • Chondrogenesis / physiology*
  • Cytokines / metabolism*
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*

Substances

  • Carrier Proteins
  • Cytokines
  • pleiotrophin

Grants and funding

This work was partially supported by EFS Ile de France, University Paris Est and by the 7th Framework Program of the European Commission through the project REBORNE #241879. Thibault Bouderlique: doctoral fellowship was supported by the French Ministere de l’Enseignement et de la Recherche. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.