Galectin-9 accelerates transforming growth factor beta3-induced differentiation of human mesenchymal stem cells to chondrocytes.
Galectin-9 (Gal-9), a beta-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 beta3 (TGFbeta3), 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 TGFbeta-mediated chondrogenesis. In pellets, addition of Gal-9 significantly enhanced TGFbeta3-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 TGFbeta3. When MSCs were co-stimulated with Gal-9, the class switch occurred on day 21. In addition, Gal-9 synergistically enhanced TGFbeta3-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.
Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Kita-Gun, Kagawa, Japan.
Tomohiro
T
Arikawa
Akihiro
A
Matsukawa
Kota
K
Watanabe
Ken-Mei
KM
Sakata
Masako
M
Seki
Megumi
M
Nagayama
Keisuke
K
Takeshita
Kanako
K
Ito
Toshiro
T
Niki
Souichi
S
Oomizu
Rika
R
Shinonaga
Naoki
N
Saita
Mitsuomi
M
Hirashima
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002356:Cartilage / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects; D005260:Female; D037161:Galectins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology*
D037161:Galectins; D051899:Smad2 Protein; D053782:Transforming Growth Factor beta3