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

14 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

Fingerprint

Galectins
Transforming Growth Factors
Chondrocytes
Mesenchymal Stromal Cells
Chondrogenesis
Cartilage
Joints
Phosphorylation
Galactosides
Experimental Arthritis
Adaptive Immunity
Proteoglycans
Lectins
Innate Immunity

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Galectin-9 accelerates transforming growth factor β3-induced differentiation of human mesenchymal stem cells to chondrocytes. / Arikawa, Tomohiro; Matsukawa, Akihiro; Watanabe, Kota; Sakata, Ken mei; Seki, Masako; Nagayama, Megumi; Takeshita, Keisuke; Ito, Kanako; Niki, Toshiro; Oomizu, Souichi; Shinonaga, Rika; Saita, Naoki; Hirashima, Mitsuomi.

In: Bone, Vol. 44, No. 5, 05.2009, p. 849-857.

Research output: Contribution to journalArticle

Arikawa, T, Matsukawa, A, Watanabe, K, Sakata, KM, 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, vol. 44, no. 5, pp. 849-857. https://doi.org/10.1016/j.bone.2009.01.365
Arikawa, Tomohiro ; Matsukawa, Akihiro ; Watanabe, Kota ; Sakata, Ken mei ; Seki, Masako ; Nagayama, Megumi ; Takeshita, Keisuke ; Ito, Kanako ; Niki, Toshiro ; Oomizu, Souichi ; Shinonaga, Rika ; Saita, Naoki ; Hirashima, Mitsuomi. / Galectin-9 accelerates transforming growth factor β3-induced differentiation of human mesenchymal stem cells to chondrocytes. In: Bone. 2009 ; Vol. 44, No. 5. pp. 849-857.
@article{34e321981d0249a188e35cdab8301780,
title = "Galectin-9 accelerates transforming growth factor β3-induced differentiation of human mesenchymal stem cells to chondrocytes",
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.",
keywords = "Cartilage repair, Chondrogenesis, Galectin-9, Human mesenchymal stem cell, TGFβ3",
author = "Tomohiro Arikawa and Akihiro Matsukawa and Kota Watanabe and Sakata, {Ken mei} and Masako Seki and Megumi Nagayama and Keisuke Takeshita and Kanako Ito and Toshiro Niki and Souichi Oomizu and Rika Shinonaga and Naoki Saita and Mitsuomi Hirashima",
year = "2009",
month = "5",
doi = "10.1016/j.bone.2009.01.365",
language = "English",
volume = "44",
pages = "849--857",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Galectin-9 accelerates transforming growth factor β3-induced differentiation of human mesenchymal stem cells to chondrocytes

AU - Arikawa, Tomohiro

AU - Matsukawa, Akihiro

AU - Watanabe, Kota

AU - Sakata, Ken mei

AU - Seki, Masako

AU - Nagayama, Megumi

AU - Takeshita, Keisuke

AU - Ito, Kanako

AU - Niki, Toshiro

AU - Oomizu, Souichi

AU - Shinonaga, Rika

AU - Saita, Naoki

AU - Hirashima, Mitsuomi

PY - 2009/5

Y1 - 2009/5

N2 - 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.

AB - 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.

KW - Cartilage repair

KW - Chondrogenesis

KW - Galectin-9

KW - Human mesenchymal stem cell

KW - TGFβ3

UR - http://www.scopus.com/inward/record.url?scp=63449120076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63449120076&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2009.01.365

DO - 10.1016/j.bone.2009.01.365

M3 - Article

C2 - 19442617

AN - SCOPUS:63449120076

VL - 44

SP - 849

EP - 857

JO - Bone

JF - Bone

SN - 8756-3282

IS - 5

ER -