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A 3D System for Culturing Human Articular Chondrocytes in Synovial Fluid
Published on: January 31, 2012
Endogenous versus exogenous growth factor regulation of articular chondrocytes
Shuiliang Shi1, Albert G Chan, Scott Mercer
1Department of Orthopaedic Surgery, Indiana University School of Medicine, 541 Clinical Drive, CL600, Indianapolis, Indiana, 46202-5111.
Abstract:
Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-β1 stimulated these reparative functions, while endogenous TGF-β1 had little effect. Endogenous TGF-β1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-β1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form.
Insights
Delivery method impacts growth factor effectiveness for cartilage repair. Insulin-like growth factor-I (IGF-I) works well with gene or protein therapy, but transforming growth factor-beta1 (TGF-β1) gene therapy is less effective due to activation issues.
Area of Science:
- Biochemistry
- Regenerative Medicine
- Cell Biology
Background:
- Articular chondrocytes are key targets for cartilage repair.
- Growth factors can be delivered via exogenous proteins or gene therapy for endogenous production.
- The optimal delivery method for growth factors in cartilage repair remains unclear.
Purpose of the Study:
- To compare the effectiveness of exogenous versus endogenous delivery of insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1) on articular chondrocyte function.
- To investigate the influence of delivery method on chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression.
Main Methods:
- Adult bovine articular chondrocytes were treated with recombinant IGF-I and TGF-β1 proteins (exogenous).
- Chondrocytes were also treated with genes encoding IGF-I and TGF-β1 for endogenous production (gene therapy).
- Effects on DNA content, glycosaminoglycan production, and aggrecan gene expression were measured.
Main Results:
- IGF-I demonstrated similar anabolic effects on chondrocytes regardless of whether it was delivered exogenously or endogenously.
- Exogenous TGF-β1 significantly stimulated chondrocyte reparative functions.
- Endogenous TGF-β1 showed limited effects unless the transgene product was activated, suggesting challenges in latent complex conversion.
Conclusions:
- Effective growth factor delivery strategies for articular cartilage repair vary depending on the specific growth factor.
- Both gene therapy and protein therapy are viable options for IGF-I delivery.
- TGF-β1 gene therapy efficacy may be limited by chondrocytes' capacity to activate the latent form of the growth factor.
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