title: Diverse effects of type II collagen on osteogenic and adipogenic differentiation of mesenchymal stem cells.
abstract: Type II collagen is known to modulate chondrogenesis of mesenchymal stem cells (MSCs). In this study, MSCs from human bone marrow aspirates were used to study the modulating effects of type II collagen on MSC differentiation during the early stages of osteogenesis and adipogenesis. With osteogenic induction, MSCs cultured on the type II collagen-coated surface showed an enhanced calcium deposition level with increasing mRNA expressions of RUNX2, osteocalcin, and alkaline phosphatase. A synthetic integrin binding peptide, which specifically interacts with the I-domain of α(1)β(1)/α(2)β(1) integrins significantly blocks the mineralization-enhancing effect of type II collagen. MSCs attached on the type II collagen-coated plates exhibited expanded cell morphology with increasing spreading area, and the pretreatment of cells with integrin α(1)β(1) or α(2)β(1)-blocking antibody reduced the effect. The phosphorylation levels of FAK, ERK, and JNK significantly increased in the MSCs that attached on the type II collagen-coated plates. On the contrary, the mineralization-enhancing effect of type II collagen was diminished by JNK and MEK inhibitors. Furthermore, type II collagen blocked the adipogenic differentiation of MSCs, and this effect is rescued by JNK and MEK inhibitors. In conclusion, type II collagen facilitates osteogenesis and suppresses adipogenesis during early stage MSC differentiation. Such effects are integrin binding-mediated and conducted through FAK-JNK and/or FAK-ERK signaling cascades. These results inspire a novel strategy encompassing type II collagen in bone tissue engineering.
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
authors.forename: Li-Hsuan
authors.initials: LH
authors.lastname: Chiu
authors.forename: Tien-Shun
authors.initials: TS
authors.lastname: Yeh
authors.forename: Huei-Mei
authors.initials: HM
authors.lastname: Huang
authors.forename: Sy-Jye
authors.initials: SJ
authors.lastname: Leu
authors.forename: Charng-Bin
authors.initials: CB
authors.lastname: Yang
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Tsai
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000368:Aged; D000469:Alkaline Phosphatase / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D048430:Cell Shape; D002478:Cells, Cultured; D024043:Collagen Type II / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D039222:Integrin alpha1beta1 / Q000378:metabolism; D038982:Integrin alpha2beta1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D050659:Core Binding Factor Alpha 1 Subunit; D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C493709:RUNX2 protein, human; D015675:Osteocalcin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase; D002118:Calcium