title: Exogenous Heparan Sulfate Enhances the TGF-β3-Induced Chondrogenesis in Human Mesenchymal Stem Cells by Activating TGF-β/Smad Signaling.
abstract: Heparan sulfate (HS) interacts with growth factors and has been implicated in regulating chondrogenesis. However, the effect of HS on TGF-β-mediated mesenchymal stem cell (MSC) chondrogenesis and molecular mechanisms remains unknown. In this study, we explored the effects of exogenous HS alone and in combination with TGF-β3 on chondrogenic differentiation of human MSCs and possible signal mechanisms. The results indicated that HS alone had no obvious effects on chondrogenic differentiation of human MSCs and TGF-β/Smad2/3 signal pathways. However, the combined TGF-β3/HS treatment resulted in a significant increase in GAG synthesis, cartilage matrix protein secretion, and cartilage-specific gene expression compared to cells treated with TGF-β3 alone. Furthermore, HS inhibited type III TGF-β receptors (TβRIII) expression and increased TGF-β3-mediated ratio of the type II (TβRII) to the type I (TβRI) TGF-β receptors and phosphorylation levels of Smad2/3. The inhibitor of the TGF-β/Smad signal, SB431542, not only completely inhibited HS-stimulated TGF-β3-mediated Smad2/3 phosphorylation but also completely inhibited the effects of HS on TGF-β3-induced chondrogenic differentiation. These results demonstrate exogenous HS enhances TGF-β3-induced chondrogenic differentiation of human MSCs by activating TGF-β/Smad2/3 signaling.
authors.affiliation: Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Spine Surgery, Sun Yat-sen Memorial Hospital, Guangzhou 510120, China.
authors.forename: Chengjie
authors.initials: C
authors.lastname: Lian
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Taifeng
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Spine Surgery, Sun Yat-sen Memorial Hospital, Guangzhou 510120, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Spine Surgery, Sun Yat-sen Memorial Hospital, Guangzhou 510120, China.
authors.forename: Zizhao
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Xu