title: Periostin Upregulates Wnt/β-Catenin Signaling to Promote the Osteogenesis of CTLA4-Modified Human Bone Marrow-Mesenchymal Stem Cells.
abstract: The enhanced osteogenesis of mesenchymal stem cells (MSCs) modified by expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) has been shown in previous studies, but the mechanism remains unknown. Here we found that the bone repair effect of CTLA4-modified MSCs in demineralized bone matrix (DBM) in a rabbit radius defect model was significantly better than that observed for unmodified MSCs in DBM or DBM alone, and the periostin (POSTN) expression in CTLA4-modified MSCs was significantly higher than that in unmodified MSCs both in vivo and in vitro. In addition, we also found that treatment of CTLA4-modified MSCs with soluble POSTN could inhibit the glycogen synthase kinase-3β activity and increase β-catenin expression through up-regulation of lipoprotein-related protein-6 phosphorylation to promote osteogenic differentiation, but blocking of integrin αvβ3, a receptor of POSTN, could suppress these effects. Our data demonstrated that POSTN expressed in response to CTLA4 can promote the osteogenesis of xenotransplanted MSCs through interaction with Wnt/β-catenin pathway.
authors.affiliation: Department of Orthopaedics, National &Regional United Engineering Laboratory, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, National &Regional United Engineering Laboratory, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Keyu
authors.initials: K
authors.lastname: Luo
authors.affiliation: Department of Orthopaedics, National &Regional United Engineering Laboratory, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Rong
authors.affiliation: Department of Orthopaedics, National &Regional United Engineering Laboratory, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, National &Regional United Engineering Laboratory, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of Orthopaedics, National &Regional United Engineering Laboratory, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, National &Regional United Engineering Laboratory, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, National &Regional United Engineering Laboratory, Southwest Hospital, Third Military Medical University, Chongqing, China.|Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China.
authors.forename: Shiwu
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Orthopaedics, National &Regional United Engineering Laboratory, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, National &Regional United Engineering Laboratory, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Dai
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D060908:CTLA-4 Antigen / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D011817:Rabbits; D060449:Wnt Signaling Pathway; D014945:Wound Healing
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human