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

• Published in: The FEBS journal Vol. 283; no. 9; pp. 1689 - 1700
• Main Authors: Xu, Jun, E, Xiao‐Qiang, Wang, Nan‐Xiang, Wang, Mo‐Nan, Xie, Huan‐Xin, Cao, Yan‐Hui, Sun, Li‐Hua, Tian, Jun, Chen, Hua‐Jiang, Yan, Jing‐Long
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.05.2016
• Subjects: Aggrecan; Aggrecans - genetics; Aggrecans - metabolism; Animals; Biomarkers; BMP7; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Bone morphogenetic protein 7; Bone Morphogenetic Protein 7 - genetics; Bone Morphogenetic Protein 7 - metabolism; Cell differentiation; Chondrocytes - metabolism; Chondrocytes - pathology; Chondroitin sulfate; Collagen (type II); Collagen Type II - genetics; Collagen Type II - metabolism; Columns (process); Degeneration; Differentiation (biology); Disease Models, Animal; Diseases; Effectiveness; Electrochemical machining; Extracellular matrix; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Feasibility; Feasibility studies; Flexibility; Gene Expression Regulation; Genetic Vectors - chemistry; Genetic Vectors - metabolism; Glucuronosyltransferase - genetics; Glucuronosyltransferase - metabolism; Glycosaminoglycans - metabolism; Homeostasis; Humans; Implantation; Intervertebral Disc - metabolism; Intervertebral Disc - pathology; intervertebral disc degeneration; Intervertebral Disc Degeneration - genetics; Intervertebral Disc Degeneration - metabolism; Intervertebral Disc Degeneration - pathology; Intervertebral Disc Degeneration - therapy; Intervertebral discs; Keratin; Keratin-19 - genetics; Keratin-19 - metabolism; Keratin-8 - genetics; Keratin-8 - metabolism; Lentivirus - genetics; Lentivirus - metabolism; Mesenchymal Stem Cell Transplantation; mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Nuclei; Nucleus pulposus; Overexpression; Rabbits; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal Transduction; Smad; Smad protein; Smad1 Protein - antagonists & inhibitors; Smad1 Protein - genetics; Smad1 Protein - metabolism; Sox9 protein; SOX9 Transcription Factor - genetics; SOX9 Transcription Factor - metabolism; Spine; Stability; Stem cells; Sulfates; Surgical implants; Survival; Therapy; intervertebral disc degeneration; Smad; BMP7; mesenchymal stem cells; nucleus pulposus
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.13695

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. Overexpression of BMP7 induced differentiation of bone marrow mesenchymal stem cells (BMSCs) towards a nucleus pulposus (NP) phenotype. In vivo analysis in a rabbit model of disc degeneration showed that implantation of BMP7‐overexpressing BMSCs promoted cell differentiation and proliferation in the NP, and these effects were mediated by the Smad pathway. These results suggest potential therapeutic avenues for the treatment of disc diseases.