Alginate encapsulation impacts the insulin-like growth factor-I system of monolayer-expanded equine articular chondrocytes and cell response to interleukin-1beta.
Abstract: Alginate hydrogel culture has been shown to reestablish chondrocytic phenotype following monolayer expansion; however, previous studies have not adequately addressed how culture conditions affect the signaling systems responsible for chondrocyte metabolic activity. Here we investigate whether chondrocyte culture history influences the insulin-like growth factor-I (IGF-I) signaling system and its regulation by interleukin-1 (IL-1). Articular chondrocytes (ACs) from equine stifle joints were expanded by serial passage and were either encapsulated in alginate beads or maintained in monolayer culture for 10 days. Alginate-derived cells (ADCs) and monolayer-derived cells (MDCs) were then plated at high density, stimulated with IL-1beta (1 and 10 ng/mL) or IGF-I (50 ng/mL) for 48 h, and assayed for levels of type I IGF receptor (IGF-IR), IGF binding proteins (IGFBPs), and endogenously secreted IGF-I. Intermediate alginate culture yielded relatively low IGF-IR levels that increased in response to IL-1beta, whereas higher receptor levels on MDCs were reduced by cytokine. MDCs also secreted substantially more IGFBP-2, the predominant binding protein in conditioned media (CM), though IL-1beta suppressed levels for both cell populations. Concentrations of autocrine/paracrine IGF-I paralleled IGFBP-2 secretion. Disparate basal levels of IGF-IR and IGFBP-2, but not IGF-I, were attributed to relative transcript expression. Systemic differences coincided with varied effects of IL-1beta and IGF-I on cell growth and type I collagen expression. We conclude that culture strategy impacts the IGF-I signaling system of ACs, potentially altering their capacity to mediate cartilage repair. Consideration of hormonal regulators may be an essential element to improve chondrocyte culture protocols used in tissue engineering applications.
Publication Date: 2007-05-24 PubMed ID: 17518712DOI: 10.1089/ten.2006.0345Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
Summary
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The research studies how the encapsulation of horse joint cells with alginate affects their response to insulin-like growth factor-I and interleukin-1. The encapsulation method was found to influence the signaling systems of the cell that regulate metabolic activity.
Background of the Study
- This study is about the impact of culturing equine articular chondrocytes (type of cells present in horses’ joints) in alginate hydrogel. This method is known to restore these cells’ character after layer expansion.
- The research focused on how the IGF-I (Insulin-like Growth Factor-I) system, an important element in the metabolic activity of chondrocytes, is influenced by the culture method and how it is affected by interleukin-1 (IL-1), a group of cytokines proteins that play central roles in the regulation of immune responses.
Methodology
- Chondrocytes were encapsulated in alginate beads or maintained in monolayer culture for 10 days. After this, the cells were plated at high density and stimulated with IL-1beta or IGF-I.
- The researchers assessed the levels of type I IGF receptor (IGF-IR), IGF binding proteins (IGFBPs), and endogenously secreted IGF-I in response to the two growth factors. The effects of these factors on cell growth and type I collagen expression were evaluated.
Results
- Alginate-derived cells had lower IGF-IR levels which increased in response to IL-1beta, while monolayer-derived cells had higher IGF-IR levels that were reduced by the same cytokine.
- Monolayer-derived cells secrete more IGFBP-2, the predominant binding protein, but IL-1beta lowered the levels in both cell populations. The secretion of autocrine/paracrine IGF-I was correlated with the levels of IGFBP-2.
- Differences in the IGF-IR and IGFBP-2 levels were attributed to the relative transcript expression but not IGF-I.
- IL-1beta and IGF-I influenced cell growth and type I collagen expression in diverse ways, which was linked to systemic differences in the cells.
Conclusions
- The researchers found that the way chondrocytes are cultured significantly affects the IGF-I system, which could in turn influence their capacity to mediate repair in cartilage.
- This suggests that hormonal regulators should be considered when improving chondrocyte culture protocols for use in tissue engineering applications.
Cite This Article
APA
Porter RM, Akers RM, Howard RD, Forsten-Williams K.
(2007).
Alginate encapsulation impacts the insulin-like growth factor-I system of monolayer-expanded equine articular chondrocytes and cell response to interleukin-1beta.
Tissue Eng, 13(6), 1333-1345.
https://doi.org/10.1089/ten.2006.0345 Publication
Researcher Affiliations
- Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0211, USA.
MeSH Terms
- Alginates / chemistry
- Animals
- Biocompatible Materials / chemistry
- Cartilage, Articular / cytology
- Cartilage, Articular / drug effects
- Cartilage, Articular / physiology
- Cell Culture Techniques / methods
- Cell Proliferation / drug effects
- Cells, Cultured
- Chondrocytes / cytology
- Chondrocytes / drug effects
- Chondrocytes / physiology
- Dose-Response Relationship, Drug
- Female
- Glucuronic Acid / chemistry
- Hexuronic Acids / chemistry
- Horses
- Insulin-Like Growth Factor I / administration & dosage
- Insulin-Like Growth Factor I / metabolism
- Interleukin-1beta / administration & dosage
- Interleukin-1beta / metabolism
- Tissue Engineering / methods
Grant Funding
- AR046414 / NIAMS NIH HHS
Citations
This article has been cited 3 times.- Hu T, Lo ACY. Collagen-Alginate Composite Hydrogel: Application in Tissue Engineering and Biomedical Sciences. Polymers (Basel) 2021 Jun 2;13(11).
- Bratlie KM, York RL, Invernale MA, Langer R, Anderson DG. Materials for diabetes therapeutics. Adv Healthc Mater 2012 May;1(3):267-84.
- Weimer A, Madry H, Venkatesan JK, Schmitt G, Frisch J, Wezel A, Jung J, Kohn D, Terwilliger EF, Trippel SB, Cucchiarini M. Benefits of recombinant adeno-associated virus (rAAV)-mediated insulinlike growth factor I (IGF-I) overexpression for the long-term reconstruction of human osteoarthritic cartilage by modulation of the IGF-I axis. Mol Med 2012 May 9;18(1):346-58.
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