title: Inhibition of SLC7A11 by Sulfasalazine Enhances Osteogenic Differentiation of Mesenchymal Stem Cells by Modulating BMP2/4 Expression and Suppresses Bone Loss in Ovariectomized Mice.
abstract: An imbalance in osteogenesis and adipogenesis is a crucial pathological factor in the development of osteoporosis. Many attempts have been made to develop drugs to prevent and treat this disease. In the present study, we investigated the phenomenon whereby downregulation of SLC7A11 significantly enhanced the osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro, and promoted the bone formation in vivo. Sulfasalazine (SAS), an inhibitor of SLC7A11, increased the osteogenic potential effectively. Mechanistically, inhibition of SLC7A11 by SAS treatment or knockdown of SLC7A11 increased BMP2/4 expression dramatically. In addition, we detected increased Slc7a11 expression in bone marrow MSCs of ovariectomized (OVX) mice. Remarkably, SAS treatment attenuated bone loss in ovariectomized mice. Together, our data suggested that SAS could be used to treat osteoporosis by enhancing osteogenic differentiation of MSCs. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Chanyuan
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Longwei
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Yunsong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.|National Engineering Lab for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D027182:Amino Acid Transport System y+ / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001862:Bone Resorption / Q000188:drug therapy* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010012:Osteogenesis / Q000187:drug effects*; D010024:Osteoporosis / Q000201:enzymology / Q000473:pathology; D010052:Ovariectomy; D012460:Sulfasalazine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D027182:Amino Acid Transport System y+; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004791:Enzyme Inhibitors; C118895:SLC7A11 protein, human; D012460:Sulfasalazine
keywords: BONE MORPHOGENETIC PROTEIN; OSTEOGENIC DIFFERENTIATION; OSTEOPOROSIS; SLC7A11; SULFASALAZINE