Impact of dexamethasone concentration on cartilage tissue formation from human synovial derived stem cells in vitro

Ryota Chijimatsu, Masato Kobayashi, Kosuke Ebina, Toru Iwahashi, Yosuke Okuno, Makoto Hirao, Atsunori Fukuhara, Norimasa Nakamura, Hideki Yoshikawa

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Human synovial mesenchymal stem cells (hSMSCs) are a promising cell source for cartilage regeneration because of their superior chondrogenic potential in vitro. This study aimed to further optimize the conditions for inducing chondrogenesis of hSMSCs, focusing on the dose of dexamethasone in combination with transforming growth factor-β3 (TGFβ3) and/or bone morphogenetic protein-2 (BMP2). When hSMSCs-derived aggregates were cultured with TGFβ3, dexamethasone up to 10 nM promoted chondrogenesis, but attenuated it with heterogeneous tissue formation when used at concentrations over than 100 nM. On the other hands, BMP2-induced chondrogenesis was remarkably disturbed in the presence of more than 10 nM dexamethasone along with unexpected adipogenic differentiation. In the presence of both TGFβ3 and BMP2, dexamethasone dose dependently promoted cartilaginous tissue formation as judged by tissue volume, proteoglycan content, and type 2 collagen expression, whereas few adipocytes were detected in the formed tissue when cultures were supplemented with over 100 nM dexamethasone. Even in chondrogenic conditions, dexamethasone thus affected hSMSCs differentiation not only toward chondrocytes, but also towards adipocytes dependent on the dose and combined growth factor. These findings have important implications regarding the use of glucocorticoids in in vitro tissue engineering for cartilage regeneration using hSMSCs.

Original languageEnglish
Pages (from-to)819-829
Number of pages11
JournalCytotechnology
Volume70
Issue number2
DOIs
Publication statusPublished - Apr 1 2018
Externally publishedYes

Keywords

  • Adipogenesis
  • Cartilage regeneration
  • Chondrogenesis
  • Dexamethasone
  • Human synovial
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Clinical Biochemistry
  • Cell Biology

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