Gene expression and proliferation analysis in young, aged, and osteoarthritic sheep chondrocytes effect of growth factor treatment

J Orthop Res. 2006 Nov;24(11):2087-94. doi: 10.1002/jor.20245.

Abstract

Cartilage is a support tissue with a poor capacity to self-repair. Its cells, chondrocytes, are responsible for synthesizing and renewing the matrix that surrounds them in a constant turnover mechanism. Autologous chondrocyte implantation (ACI) is one of the techniques that promises to be an alternative to common strategies for chondral lesions. To apply this technique, a large amount of cells must be obtained. In our work, we studied the state of cells from different cartilage (young, aged, and osteoarthritic sheep) cultured in monolayer by analyzing their proliferation rate using bromodeoxyuridine and their gene expression profile by RT-PCR. A decrease was found in expression of type II collagen and aggrecan in aged, osteoarthritic, and passaged chondrocytes. Treatment of cells with growth factors aFGF, IGF-I, TGF-beta, and OP-1 improved the proliferation rate in all cells studied and stimulated gene expression of type II collagen, aggrecan, and TGF-beta. Osteoarthritic cells showed a poor response according to matrix gene expression, while young cells responded properly, and aged chondrocytes showed a moderate response. These results suggest that the state of cartilage may affect the behavior of cultured chondrocytes.

MeSH terms

  • Aggrecans / genetics
  • Aggrecans / metabolism
  • Aging / physiology
  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Disease Models, Animal
  • Gene Expression / drug effects*
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Osteoarthritis / pathology
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sheep
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • Aggrecans
  • Collagen Type II
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Bromodeoxyuridine