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Engineered Cartilage Maturation Regulates Cytokine Production and Interleukin-1β Response

  • Symposium: Clinically Relevant Strategies for Treating Cartilage and Meniscal Pathology
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Because the injured joint has an actively inflammatory environment, the survival and repair potential of cartilage grafts may be influenced by inflammatory processes. Understanding the interactions of those processes with the graft may lead to concepts for pharmacologic or surgical solutions allowing improved cartilage repair.

Questions/purposes

We asked whether the maturation level of cartilaginous tissues generated in vitro by expanded human articular chondrocytes (HACs) modulate (1) the spontaneous production of cytokines and (2) the response to interleukin (IL)-1β.

Methods

Twelve pellets/donor prepared with monolayer-expanded HACs (n = 6 donors) were evaluated at six different culture times for mRNA expression (n = 72) and spontaneous baseline release of monocyte chemoattractant protein (MCP)-1, IL-8, and transforming growth factor (TGF)-β1 (n = 72). We cultured 24 pellets/donor from each of four donors for 1 or 14 days (defined as immature and mature, respectively) and exposed the pellets to IL-1β for 3 days. MCP-1, IL-8, TGF-β1, and metalloprotease (MMP)-1 and MMP-13 were quantified in pellets and culture supernatants.

Results

By increasing culture time, the spontaneous release of IL-8 and MCP-1 decreased (12.0- and 5.5-fold, respectively), whereas that of TGF-β1 increased (5.4-fold). As compared with immature pellets, mature pellets responded to IL-1β by releasing lower amounts of MMP-1 (2.9-fold) and MMP-13 (1.7-fold) and increased levels of IL-8, MCP-1, and TGF-β1 (1.5-, 5.0-, and 7.5-fold, respectively). IL-8 and MCP-1 promptly returned to baseline on withdrawal of IL-1β.

Conclusions

Our observations suggest more mature cartilaginous tissues are more resistant to IL-1β exposure and can activate chemokines required to initiate tissue repair processes.

Clinical Relevance

The implantation of more mature cartilaginous tissues might provide superior graft survival and improve/accelerate cartilage repair.

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Acknowledgments

We thank Professor Marcel Jakob for the procurement of cartilage samples. We are grateful to Mrs F. Wolf and Jennifer Frueh for their assistance with Luminex assay and to Dr. Sylvie Miot for her precious help in the culture of chondrocytes and in the biochemical analyses.

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Authors and Affiliations

  1. Department of Biomedicine, University Hospital Basel, Basel, Switzerland

    Silvia Francioli PhD, Ivan Martin PhD & Andrea Barbero PhD

  2. Laboratorio di Immunologia e Genetica, Istituto di Ricerca Codivilla Putti, Istituto Ortopedico Rizzoli, Bologna, Italy

    Carola Cavallo PhD & Brunella Grigolo PhD

  3. Institute for Surgical Research & Hospital Management, University Hospital Basel, Hebelstrasse 20, ZLF, Room 405, 4031, Basel, Switzerland

    Ivan Martin PhD

Authors
  1. Silvia Francioli PhD
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  2. Carola Cavallo PhD
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  3. Brunella Grigolo PhD
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  4. Ivan Martin PhD
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  5. Andrea Barbero PhD
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Corresponding author

Correspondence to Ivan Martin PhD.

Additional information

One or more of the authors (IM) received funding from the Swiss National Science Foundation (Grant 3200B0-110054).

Each author certifies that his or her institution has approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and informed consent for participation in the study was obtained.

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Francioli, S., Cavallo, C., Grigolo, B. et al. Engineered Cartilage Maturation Regulates Cytokine Production and Interleukin-1β Response. Clin Orthop Relat Res 469, 2773–2784 (2011). https://doi.org/10.1007/s11999-011-1826-x

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  • DOI: https://doi.org/10.1007/s11999-011-1826-x

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