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

• DOI: 10.1111/febs.13695
• Publication Date: 2016-03-01T08:01:06Z
• Authors: Jun Xu; Xiao‐Qiang E; Nan‐Xiang Wang; Mo‐Nan Wang; Huan‐Xin Xie; Yan‐Hui Cao; Li‐Hua Sun; Jun Tian; Hua‐Jiang Chen; Jing‐Long Yan
• Keywords: Keratin-19; 0301 basic medicine; 2. Zero hunger; 0303 health sciences; Bone Morphogenetic Protein 7; Keratin-8; Genetic Vectors; Lentivirus; Bone Marrow Cells; Mesenchymal Stem Cells; Intervertebral Disc Degeneration; Mesenchymal Stem Cell Transplantation; Extracellular Matrix; Disease Models, Animal; 03 medical and health sciences; Chondrocytes; Gene Expression Regulation; Animals; Humans; Aggrecans; Glucuronosyltransferase; Intervertebral Disc; Collagen Type II; Glycosaminoglycans

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.