, Volume 70, Issue 2, pp 819–829 | Cite as

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
Original Article


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.


Dexamethasone Human synovial Mesenchymal stem cells Chondrogenesis Adipogenesis Cartilage regeneration 



The authors thank Fumiko Hirayama and Yukiko Eguchi for their technical support.

Compliance with ethical standards

Conflict of interest

All authors have no conflict of interest to declare.

Supplementary material

10616_2018_191_MOESM1_ESM.tif (11.5 mb)
Supplementary Fig. 1. Results obtained using hSMSCs isolated from other two donors; related to Fig. 2. Scale bars = 500 μm. (TIFF 11793 kb)
10616_2018_191_MOESM2_ESM.tif (15.5 mb)
Supplementary Fig. 2. Results obtained using hSMSCs isolated from other two donors; related to Fig. 4. Scale bars = 500 μm (left panels) and 50 μm (right panels). (TIFF 15848 kb)
10616_2018_191_MOESM3_ESM.tif (26 mb)
Supplementary Fig. 3. Effect of dexamethasone compared to that of other types of glucocorticoids (prednisolone, betamethasone, and fluocinolone acetonide) on two-dimension micromass cultured with BMP2 (50 ng/mL). Alcian blue and Oil red O staining at day 7 culture. Scale bars = 1 mm (left panels) and 100 μm (right panels). (TIFF 26588 kb)


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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Ryota Chijimatsu
    • 1
  • Masato Kobayashi
    • 1
  • Kosuke Ebina
    • 1
  • Toru Iwahashi
    • 1
  • Yosuke Okuno
    • 2
  • Makoto Hirao
    • 1
  • Atsunori Fukuhara
    • 2
  • Norimasa Nakamura
    • 1
    • 3
    • 4
  • Hideki Yoshikawa
    • 1
  1. 1.Graduate School of Medicine, Orthopaedic SurgeryOsaka UniversitySuitaJapan
  2. 2.Graduate School of Medicine, Metabolic MedicineOsaka UniversitySuitaJapan
  3. 3.Institute for Medical Science in SportsOsaka Health Science UniversityOsakaJapan
  4. 4.Center for Advanced Medical Engineering and InformaticsOsaka UniversitySuitaJapan

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