[Human chondrocyte responsiveness to bone morphogenetic protein-2 after their in vitro dedifferentiation: potential use of bone morphogenetic protein-2 for cartilage cell therapy]

Pathol Biol (Paris). 2009 Jun;57(4):282-9. doi: 10.1016/j.patbio.2008.04.013. Epub 2008 Jun 6.
[Article in French]

Abstract

Aim of the study: Cartilage has a limited capacity for healing after trauma. Autologous chondrocyte implantation is widely used for the treatment of patients with focal damage to articular cartilage. Chondrocytes are isolated from biopsy specimen, cultured in monolayers on plastic then transplanted over the cartilage defect. However, chondrocyte amplification on plastic triggers their dedifferentiation. This phenomenon is characterized by loss of expression of type II collagen, the most abundant cartilage protein. The challenge for autologous chondrocyte implantation is to provide patients with well-differentiated cells. The aim of the present study was to test the capability of bone morphogenetic protein (BMP)-2 to promote redifferentiation of human chondrocytes after their expansion on plastic.

Materials and methods: Chondrocytes extracted from nasal cartilage obtained after septoplasty were serially cultured in monolayers. After one, two or three passages, BMP-2 was added to the culture medium. The cellular phenotype was characterized at the gene level by using RT-PCR. The expression of genes coding for type II procollagen with the ratio of IIB/IIA forms, aggrecan, Sox9, osteocalcin and type I procollagen was monitored.

Results: Our results show that BMP-2 can stimulate chondrogenic expression of the chondrocytes amplified on plastic, without inducing osteogenic expression. However, this stimulatory effect decreases with the number of passages.

Conclusion: The efficiency of autologous chondrocyte implantation could be improved by using chondrocytes treated with BMP-2 during their in vitro preparation.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aggrecans / biosynthesis
  • Aggrecans / genetics
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Cell Dedifferentiation / drug effects
  • Cell- and Tissue-Based Therapy / methods
  • Cells, Cultured / cytology
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Chondrocytes / cytology
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Collagen Type II / biosynthesis
  • Collagen Type II / genetics
  • Extracellular Matrix Proteins / biosynthesis*
  • Extracellular Matrix Proteins / genetics
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Male
  • Middle Aged
  • Osteocalcin / biosynthesis
  • Osteocalcin / genetics
  • Procollagen / biosynthesis
  • Procollagen / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • SOX9 Transcription Factor / biosynthesis
  • SOX9 Transcription Factor / genetics
  • Young Adult

Substances

  • Aggrecans
  • Bone Morphogenetic Protein 2
  • Collagen Type II
  • Extracellular Matrix Proteins
  • Procollagen
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Osteocalcin