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BMP 7 enhances the effect of BMSC s on extracellular matrix remodeling in a rabbit model of intervertebral disc degeneration
Author(s) -
Xu Jun,
E XiaoQiang,
Wang NanXiang,
Wang MoNan,
Xie HuanXin,
Cao YanHui,
Sun LiHua,
Tian Jun,
Chen HuaJiang,
Yan JingLong
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13695
Subject(s) - extracellular matrix , intervertebral disc , microbiology and biotechnology , chemistry , degeneration (medical) , bone morphogenetic protein 2 , extracellular , matrix metalloproteinase , anatomy , biochemistry , biology , pathology , in vitro , medicine
Intervertebral discs ( IVD s) provide stability and flexibility to the spinal column; however, IVD s, 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 ( BMSC s) over‐expressing bone morphogenetic protein 7 ( BMP 7) to promote ECM remodeling of degenerated IVD s. Lentivirus‐mediated BMP 7 over‐expression induced differentiation of BMSC s 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 BMP 7 on ECM remodeling was mediated by the Smad pathway. In vivo analysis in a rabbit model of disc degeneration showed that implantation of BMSC s over‐expressing BMP 7 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 BMP 7 on restoring ECM homeostasis in NP cells, and suggest potential strategies for improving cell therapy for the treatment of disc diseases.