Regulation of articular chondrocyte catabolic genes by growth factor interaction

Shuiliang Shi, Scott Mercer, George J. Eckert, Stephen Trippel

Research output: Contribution to journalArticle

Abstract

Osteoarthritis is characterized by a loss of articular cartilage homeostasis in which degradation exceeds formation. Several growth factors have been shown to promote cartilage formation by augmenting articular chondrocyte anabolic activity. This study tests the hypothesis that such growth factors also play an anticatabolic role. We transferred individual or combinations of the genes encoding insulin-like growth factor-I, bone morphogenetic protein-2, bone morphogenetic protein-7, transforming growth factor-β1, and fibroblast growth factor-2, into adult bovine articular chondrocytes and measured the expression of catabolic marker genes encoding A disintegrin and metalloproteinase with thrombospondin motifs-4 and -5, matrix metalloproteinases-3 and -13, and interleukin-6. When delivered individually, or in combination, these growth factor transgenes differentially regulated the direction, magnitude, and time course of expression of the catabolic marker genes. In concert, the growth factor transgenes regulated the marker genes in an interactive fashion that ranged from synergistic inhibition to synergistic stimulation. Synergistic stimulation prevailed over synergistic inhibition, reaching maxima of 15.2- and 2.7-fold, respectively. Neither the magnitude nor the time course of the effect of the transgene combinations could be predicted on the basis of the individual transgene effects. With few exceptions, the data contradict our hypothesis. The results demonstrate that growth factors that are traditionally viewed as chondrogenic tend also to promote catabolic gene expression. The competing actions of these potential therapeutic agents add an additional level of complexity to the selection of regulatory factors for restoring articular cartilage homeostasis or promoting repair.

Original languageEnglish (US)
JournalJournal of Cellular Biochemistry
DOIs
StatePublished - Jan 1 2019

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Chondrocytes
Intercellular Signaling Peptides and Proteins
Transgenes
Genes
Joints
Cartilage
Gene encoding
Articular Cartilage
Homeostasis
Bone Morphogenetic Protein 7
Matrix Metalloproteinase 13
Thrombospondins
Disintegrins
Matrix Metalloproteinase 3
Bone Morphogenetic Protein 2
Transforming Growth Factors
Metalloproteases
Fibroblast Growth Factor 2
Insulin-Like Growth Factor I
Gene expression

Keywords

  • articular chondrocytes
  • cellular regulation
  • cytokines
  • gene transfer
  • growth factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Regulation of articular chondrocyte catabolic genes by growth factor interaction. / Shi, Shuiliang; Mercer, Scott; Eckert, George J.; Trippel, Stephen.

In: Journal of Cellular Biochemistry, 01.01.2019.

Research output: Contribution to journalArticle

Shi, Shuiliang ; Mercer, Scott ; Eckert, George J. ; Trippel, Stephen. / Regulation of articular chondrocyte catabolic genes by growth factor interaction. In: Journal of Cellular Biochemistry. 2019.
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