BMP7 enhances the effect of BMSCs on extracellular matrix remodeling in a rabbit model of intervertebral disc degeneration

Autor: Hua-Jiang Chen, Jun Tian, Nan-Xiang Wang, Jun Xu, Xiao-Qiang E, Mo-Nan Wang, Jinglong Yan, Li-Hua Sun, Huan-Xin Xie, Yan-Hui Cao
Rok vydání: 2015
Předmět:
0301 basic medicine
animal structures
Cellular differentiation
Bone Morphogenetic Protein 7
Genetic Vectors
Bone Marrow Cells
Intervertebral Disc Degeneration
Mesenchymal Stem Cell Transplantation
Biochemistry
Smad1 Protein
Cell therapy
Extracellular matrix
03 medical and health sciences
0302 clinical medicine
Chondrocytes
medicine
Animals
Humans
Aggrecans
Glucuronosyltransferase
RNA
Small Interfering
Intervertebral Disc
Molecular Biology
Collagen Type II
Aggrecan
Glycosaminoglycans
Keratin-19
Chemistry
Keratin-8
Mesenchymal stem cell
Lentivirus
Intervertebral disc
Mesenchymal Stem Cells
SOX9 Transcription Factor
Cell Biology
Anatomy
Spinal column
Cell biology
Extracellular Matrix
Bone morphogenetic protein 7
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
embryonic structures
Rabbits
030217 neurology & neurosurgery
Signal Transduction
Zdroj: The FEBS journal. 283(9)
ISSN: 1742-4658
Popis: 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.
Databáze: OpenAIRE
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