IGF-1 and BMP-7 synergistically stimulate articular cartilage repairing in the rabbit knees by improving chondrogenic differentiation of bone-marrow mesenchymal stem cells

J Cell Biochem. 2019 Apr;120(4):5570-5582. doi: 10.1002/jcb.27841. Epub 2018 Nov 11.

Abstract

Knee injury is known as a frequently occurred damage related to sports, which may affect the function of cartilage. This study aims to explore whether Insulin-like growth factor 1 (IGF-1) and bone morphogenetic protein-7 (BMP-7)-modified bone-marrow mesenchymal stem cells (BMSCs) affect the repair of cartilage damage found in the knee. Primarily, BMSCs were treated with a series of pEGFP-C1, IGF-1, and BMP-7, followed by determination of IGF-1 and BMP-7 expression. A rabbit cartilage defect model was also established. Afterfward, cell morphology, viability, cartilage damage repair effect, and expression of collagen I and collagen II at the 6th and the 12th week were measured. BMSCs treated with pEGFP-C1/IGF-1, pEGFP-C1/BMP-7, and pEGFP-C1/BMP-7-IGF-1 exhibited elevated expression of BMP-7 and IGF-1. Besides, BMSCs in the P10 generation displayed decreased cell proliferation. Moreover, BMSCs treated with IGF-1, BMP-7, and IGF-1-BMP-7 showed reduced histological score and collagen I expression while elevated collagen II expression, as well as better repair effect, especially in those treated with IGF-1-BMP-7. Collectively, these results demonstrated a synergistic effect of IGF-1 and BMP-7 on the BMSC chondrogenic differentiation on the articular cartilage damage repair in the rabbit knees, highlighting its therapeutic potential for the treatment of articular cartilage damage.

Keywords: Insulin-like growth factor 1; bone morphogenetic protein-7; bone-marrow mesenchymal stem cells; cartilage damage; gene modification.

MeSH terms

  • Allografts
  • Animals
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Cells / pathology
  • Bone Morphogenetic Protein 7 / pharmacology*
  • Cartilage, Articular / injuries
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Cell Differentiation / drug effects*
  • Chondrogenesis / drug effects*
  • Insulin-Like Growth Factor I / pharmacology*
  • Knee Injuries* / metabolism
  • Knee Injuries* / pathology
  • Knee Injuries* / therapy
  • Knee Joint / metabolism*
  • Knee Joint / pathology
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Rabbits

Substances

  • Bone Morphogenetic Protein 7
  • Insulin-Like Growth Factor I