title: BMP7 enhances the effect of BMSCs on extracellular matrix remodeling in a rabbit model of intervertebral disc degeneration.
abstract: Intervertebral discs (IVDs) provide stability and flexibility to the spinal column; however, IVDs, and in particular the nucleus pulposus (NP), undergo a degenerative process characterized by changes in the disc extracellular matrix (ECM), decreased cell viability, and reduced synthesis of proteoglycan and type II collagen. Here, we investigated the efficacy and feasibility of stem cell therapy using bone marrow mesenchymal stem cells (BMSCs) over-expressing bone morphogenetic protein 7 (BMP7) to promote ECM remodeling of degenerated IVDs. Lentivirus-mediated BMP7 over-expression induced differentiation of BMSCs into an NP phenotype, as indicated by expression of the NP markers collagen type II, aggrecan, SOX9 and keratins 8 and 19, increased the content of glycosaminoglycan, and up-regulated β-1,3-glucuronosyl transferase 1, a regulator of chondroitin sulfate synthesis in NP cells. These effects were suppressed by Smad1 silencing, indicating that the effect of BMP7 on ECM remodeling was mediated by the Smad pathway. In vivo analysis in a rabbit model of disc degeneration showed that implantation of BMSCs over-expressing BMP7 promoted cell differentiation and proliferation in the NP, as well as their own survival, and these effects were mediated by the Smad pathway. The results of the present study indicate the beneficial effects of BMP7 on restoring ECM homeostasis in NP cells, and suggest potential strategies for improving cell therapy for the treatment of disc diseases.
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: E
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, China.
authors.forename: Nan-Xiang
authors.initials: NX
authors.lastname: Wang
authors.affiliation: Robotics Institute, Harbin University of Science and Technology, China.
authors.forename: Mo-Nan
authors.initials: MN
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, China.
authors.forename: Huan-Xin
authors.initials: HX
authors.lastname: Xie
authors.affiliation: Department of Intensive Care Unit (ICU), The First Affiliated Hospital of Harbin Medical University, China.
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, State/Province Key Laboratories of Biomedicine/Pharmaceutics of China, Harbin Medical University, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hua-Jiang
authors.initials: HJ
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, China.
authors.forename: Jing-Long
authors.initials: JL
authors.lastname: Yan
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics* / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D053539:Keratin-19 / Q000235:genetics / Q000378:metabolism; D053533:Keratin-8 / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics* / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051898:Smad1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D053674:Aggrecans; D055419:Bone Morphogenetic Protein 7; D024043:Collagen Type II; D006025:Glycosaminoglycans; D053539:Keratin-19; D053533:Keratin-8; D034741:RNA, Small Interfering; D055758:SOX9 Transcription Factor; D051898:Smad1 Protein; C067806:glucuronyltransferase GlcAT-1; D014453:Glucuronosyltransferase
keywords: BMP7; Smad; intervertebral disc degeneration; mesenchymal stem cells; nucleus pulposus