Effects of controlled released BMP-7 on markers of inflammation and degradation during the cultivation of human osteoarthritic chondrocytes

J Biomater Appl. 2011 Nov;26(4):419-33. doi: 10.1177/0885328210374671. Epub 2010 Jul 12.

Abstract

The aim of the present study is to investigate the effects of BMP-7 released from polylactide microspheres on the appearance of various catabolic and inflammatory cytokines secreted by osteoarthritic chondrocytes cultivated in a collagen gel. Articular chondrocytes of 15 patients suffering from osteoarthritis are transferred to a collagen type-I gel. Additionally, BMP-7 encapsulated into polylactide microspheres (50 ng BMP-7/mL gel) is added. After 14 days, gene expression and protein appearance of various genes involved in matrix turnover and inflammation are investigated by immunohistochemical staining and RT-PCR and compared to untreated controls. TNF-α, MMP-13, IL-6, IL-1β, and VEGF gene expressions are decreased in the treatment group. In contrast, BMP-7-induced matrix synthesis is not affected, leaving collagen type-II (Col-II) gene expression to be elevated, while collagen type-I (Col-I) is decreased. In summary, controlled release of low concentrated BMP-7 from polylactide microspheres leads to a decrease in gene expression of the investigated inflammation and matrix degradation markers whereas matrix synthesis is induced.

MeSH terms

  • Base Sequence
  • Biomarkers / metabolism
  • Bone Morphogenetic Protein 7 / administration & dosage*
  • Cell Culture Techniques
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism*
  • Chondrocytes / pathology
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Delayed-Action Preparations
  • Gene Expression / drug effects
  • Humans
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Microspheres
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / administration & dosage
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • BMP7 protein, human
  • Biomarkers
  • Bone Morphogenetic Protein 7
  • Collagen Type I
  • Collagen Type II
  • Cytokines
  • Delayed-Action Preparations
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • MMP13 protein, human
  • Matrix Metalloproteinase 13