title: The use of SHP-2 gene transduced bone marrow mesenchymal stem cells to promote osteogenic differentiation and bone defect repair in rat.
abstract: Bone tissue engineering is a promising approach for bone regeneration, in which growth factors play an important role. The tyrosine phosphatase Src-homology region 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by the PTPN11 gene, is essential for the differentiation, proliferation and metabolism of osteoblasts. However, SHP-2 has never been systematically studied for its effect in osteogenesis. We predicted that overexpression of SHP-2 could promote bone marrow-derived mesenchymal stem cell (BMSC)osteogenic differentiation and SHP-2 transduced BMSCs could enhance new bone formation, determined using the following study groups: (1) BMSCs transduced with SHP-2 and induced with osteoblast-inducing liquid (BMSCs/SHP-2/OL); (2) BMSCs transduced with SHP-2 (BMSCs/-SHP-2); (3) BMSCs induced with osteoblast-inducing liquid (BMSCs/OL) and (4) pure BMSCs. Cells were assessed for osteogenic differentiation by quantitative real-time polymerase chain reaction analysis, western blot analysis, alkaline phosphatase activity and alizarin red S staining. For in vivo assessment, cells were combined with beta-tricalcium phosphate scaffolds and transplanted into rat calvarial defects for 8 weeks. Following euthanasia, skull samples were explanted for osteogenic evaluation, including micro-computed tomography measurement, histology and immunohistochemistry staining. SHP-2 and upregulation of its gene promoted BMSC osteogenic differentiation and therefore represents a potential new therapeutic approach to bone repair. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1871-1881, 2016.
authors.affiliation: Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
authors.forename: Shen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, No.324 Jingwu Road, Jinan, 250021, Shandong, People's Republic of China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Mo
authors.affiliation: Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Ruan
authors.affiliation: Hawaii Gangze Inc, 421 Nahua Street, Suite 146, Honolulu, Hawaii, 96815.
authors.forename: Gang-Ming
authors.initials: GM
authors.lastname: Zou
authors.affiliation: Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
authors.forename: Cunyi
authors.initials: C
authors.lastname: Fan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology*; D014161:Transduction, Genetic; D014945:Wound Healing; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11
keywords: BMSCs; Bone repair; Osteogenesis; SHP-2; Tissue engineering; β-TCP