Galectin-9 accelerates transforming growth factor β3-induced differentiation of human mesenchymal stem cells to chondrocytes

Tomohiro Arikawa, Akihiro Matsukawa, Kota Watanabe, Ken mei Sakata, Masako Seki, Megumi Nagayama, Keisuke Takeshita, Kanako Ito, Toshiro Niki, Souichi Oomizu, Rika Shinonaga, Naoki Saita, Mitsuomi Hirashima

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Galectin-9 (Gal-9), a β-galactoside binding lectin, plays a crucial role in innate and adaptive immunity. In the rat collagen-induced arthritis model, administration of Gal-9 induced repair of existing cartilage injury even when joints were already swollen with cartilage destruction. We thus attempted to explore the role of Gal-9 in chondrocyte differentiation utilizing human mesenchymal stem cell (MSC) pellet cultures. During chondrogenesis induced by transforming growth factor β3 (TGFβ3), MSCs strongly expressed endogenous Gal-9. Expression of Gal-9 peaked on day 14 and the neutralization of endogenous Gal-9 resulted in the reduced chondrogenesis, indicating possible involvement of Gal-9 in TGFβ-mediated chondrogenesis. In pellets, addition of Gal-9 significantly enhanced TGFβ3-induced chondrogenesis, as evidenced by increasing proteoglycan content, but not cell proliferation. In the absence of Gal-9, collagen expression by MSCs switched from type I to type II on 28 days after stimulation with TGFβ3. When MSCs were co-stimulated with Gal-9, the class switch occurred on day 21. In addition, Gal-9 synergistically enhanced TGFβ3-induced phosphorylation of Smad2, though Gal-9 did not itself induce detectable Smad2 phosphorylation. These results suggest that Gal-9 has a beneficial effect on cartilage repair in injured joints by induction of differentiation of MSCs into chondrocytes.

Original languageEnglish
Pages (from-to)849-857
Number of pages9
JournalBone
Volume44
Issue number5
DOIs
Publication statusPublished - May 2009

Keywords

  • Cartilage repair
  • Chondrogenesis
  • Galectin-9
  • Human mesenchymal stem cell
  • TGFβ3

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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    Arikawa, T., Matsukawa, A., Watanabe, K., Sakata, K. M., Seki, M., Nagayama, M., Takeshita, K., Ito, K., Niki, T., Oomizu, S., Shinonaga, R., Saita, N., & Hirashima, M. (2009). Galectin-9 accelerates transforming growth factor β3-induced differentiation of human mesenchymal stem cells to chondrocytes. Bone, 44(5), 849-857. https://doi.org/10.1016/j.bone.2009.01.365