title: The effect of type II collagen on MSC osteogenic differentiation and bone defect repair.
abstract: The function of type II collagen in cartilage is well documented and its importance for long bone development has been implicated. However, the involvement of type II collagen in bone marrow derived mesenchymal stem cell (BMSC) osteogenesis has not been well investigated. This study elucidated the pivotal role of type II collagen in BMSC osteogenesis and its potential application to bone healing. Type II collagen-coated surface was found to accelerate calcium deposition, and the interaction of osteogenic medium-induced BMSCs with type II collagen-coated surface was mainly mediated through integrin α2β1. Exogenous type II collagen directly activated FAK-JNK signaling and resulted in the phosphorylation of RUNX2. In a segmental defect model in rats, type II collagen-HA/TCP-implanted rats showed significant callus formation at the reunion site, and a higher SFI (sciatic function index) scoring as comparing to other groups were also observed at 7, 14, and 21 day post-surgery. Collectively, type II collagen serves as a better modulator during early osteogenic differentiation of BMSCs by facilitating RUNX2 activation through integrin α2β1-FAK-JNK signaling axis, and enhance bone defect repair through an endochondral ossification-like process. These results advance our understanding about the cartilaginous ECM-BMSC interaction, and provide perspective for bone defect repair strategies.
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Li-Hsuan
authors.initials: LH
authors.lastname: Chiu
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 11031, Taiwan; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei 11031, Taiwan; Center for Nano Biomedicine Research, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Wen-Fu T
authors.initials: WF
authors.lastname: Lai
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Shwu-Fen
authors.initials: SF
authors.lastname: Chang
authors.affiliation: Department of Orthopaedic Surgery, Wanfang Hospital, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Chin-Chean
authors.initials: CC
authors.lastname: Wong
authors.affiliation: Department of Orthopaedic Surgery, Taipei Medical University Hospital, Taipei 11031, Taiwan.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Fan
authors.affiliation: Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
authors.forename: Chia-Lang
authors.initials: CL
authors.lastname: Fang
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 11031, Taiwan; Center for Nano Biomedicine Research, Taipei Medical University, Taipei 11031, Taiwan. Electronic address: lh.s.chiu@tmu.edu.tw.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Tsai
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002130:Calcium Phosphates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002645:Chickens; D024043:Collagen Type II / Q000494:pharmacology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D017886:Durapatite / Q000494:pharmacology; D005269:Femur / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000199:Actins; D015415:Biomarkers; D002130:Calcium Phosphates; D024043:Collagen Type II; D050659:Core Binding Factor Alpha 1 Subunit; D038982:Integrin alpha2beta1; D012333:RNA, Messenger; D017886:Durapatite; C018392:tricalcium phosphate; D002118:Calcium
keywords: Bone healing; Cell adhesion; Integrin signaling; Mesenchymal stem cell; Osteogenesis; Type II collagen