Growth factor transgenes interactively regulate articular chondrocytes

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

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Adult articular chondrocytes lack an effective repair response to correct damage from injury or osteoarthritis. Polypeptide growth factors that stimulate articular chondrocyte proliferation and cartilage matrix synthesis may augment this response. Gene transfer is a promising approach to delivering such factors. Multiple growth factor genes regulate these cell functions, but multiple growth factor gene transfer remains unexplored. We tested the hypothesis that multiple growth factor gene transfer selectively modulates articular chondrocyte proliferation and matrix synthesis. We tested the hypothesis by delivering combinations of the transgenes encoding insulin-like growth factor I (IGF-I), fibroblast growth factor-2 (FGF-2), transforming growth factor beta1 (TGF-β1), bone morphogenetic protein-2 (BMP-2), and bone morphogenetic protien-7 (BMP-7) to articular chondrocytes and measured changes in the production of DNA, glycosaminoglycan, and collagen. The transgenes differentially regulated all these chondrocyte activities. In concert, the transgenes interacted to generate widely divergent responses from the cells. These interactions ranged from inhibitory to synergistic. The transgene pair encoding IGF-I and FGF-2 maximized cell proliferation. The three-transgene group encoding IGF-I, BMP-2, and BMP-7 maximized matrix production and also optimized the balance between cell proliferation and matrix production. These data demonstrate an approach to articular chondrocyte regulation that may be tailored to stimulate specific cell functions, and suggest that certain growth factor gene combinations have potential value for cell-based articular cartilage repair. J. Cell. Biochem. 114: 908-919, 2013. © 2012 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)908-919
Number of pages12
JournalJournal of Cellular Biochemistry
Volume114
Issue number4
DOIs
StatePublished - Apr 2013

Fingerprint

Chondrocytes
Transgenes
Intercellular Signaling Peptides and Proteins
Gene transfer
Joints
Insulin-Like Growth Factor I
Bone Morphogenetic Protein 2
Cell proliferation
Cartilage
Fibroblast Growth Factor 2
Genes
Bone
Repair
Transforming Growth Factor beta1
Cell Proliferation
Bone and Bones
Glycosaminoglycans
Articular Cartilage
Osteoarthritis
Collagen

Keywords

  • ARTICULAR CHONDROCYTES
  • DNA
  • GENE THERAPY
  • GROWTH FACTORS
  • MATRIX

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Growth factor transgenes interactively regulate articular chondrocytes. / Shi, Shuiliang; Mercer, Scott; Eckert, George J.; Trippel, Stephen.

In: Journal of Cellular Biochemistry, Vol. 114, No. 4, 04.2013, p. 908-919.

Research output: Contribution to journalArticle

Shi, Shuiliang ; Mercer, Scott ; Eckert, George J. ; Trippel, Stephen. / Growth factor transgenes interactively regulate articular chondrocytes. In: Journal of Cellular Biochemistry. 2013 ; Vol. 114, No. 4. pp. 908-919.
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