title: Sonic hedgehog enhances the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells.
abstract: MSCs (mesenchymal stem cells) may be promising seed cells for tissue regeneration because of their self-renewal and multi-differentiation potential. Shh (sonic hedgehog) is involved in the skeletal formation during embryo development and skeletal regeneration. However, how Shh regulates the biological characteristics of BM-MSCs (bone marrow-derived MSCs) is poorly understood. We have investigated the effect of rShh-N (recombinant N-terminal Shh) on the proliferation and osteogenic differentiation of rBM-MSCs (rat BM-MSCs) in vitro. rBM-MSCs were treated with rShh-N at concentrations up to 200 ng/ml. Proliferation and colony-forming ability of rBM-MSCs were increased in a dose-dependent manner. rShh-N increased the ratio of cells in S and G2/M phase, as well as the number of Ki-67+ cells. In addition, ALP (alkaline phosphatase) activity and matrix mineralization were enhanced by 200 ng/ml rShh-N. Real-time PCR showed that rShh-N (200 ng/ml) up-regulated the expression of genes encoding Cbfa-1 (core-binding factor α1), osteocalcin, ALP and collagen type I in rBM-MSCs. This information reveals some potential of rShh-N in the therapeutics of bone-related diseases.
authors.affiliation: Division of Stem Cell and Tissue Engineering, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Peoples Republic of China.
authors.forename: Jia-Qin
authors.initials: JQ
authors.lastname: Cai
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Huang
authors.forename: Xiao-He
authors.initials: XH
authors.lastname: Chen
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Xie
authors.forename: Hong-Ming
authors.initials: HM
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Yang
authors.forename: Yong-Can
authors.initials: YC
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Deng
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D050660:Core Binding Factors / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins / Q000494:pharmacology / Q000502:physiology*; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D050660:Core Binding Factors; D053823:Hedgehog Proteins; D019394:Ki-67 Antigen; D011994:Recombinant Proteins; C493717:Runx2 protein, rat; C546888:Shh protein, rat; D015675:Osteocalcin; D000469:Alkaline Phosphatase