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
N1 - Funding Information:
This work was supported in partly by grants from Japanese Ministry of Education, Culture, Sports, Science, and Technology. This work was partly performed in Division of Animal Experiment and Division of Research Instrument and Equipment, Life Science Research Center, Institute of Research Promotion, Kagawa University.
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 -