A Role for Chemokines in the Induction of Chondrocyte Phenotype Modulation

Ilaria Mazzetti, Giorgia Magagnoli, Samantha Paoletti, Mariagrazia Uguccioni, Eleonora Olivotto, Roberta Vitellozzi, Luca Cattini, Andrea Facchini, Rosa Maria Borzì

Research output: Contribution to journalArticle

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Abstract

Objective. To extend the study of the chemokine receptor repertoire on human chondrocytes to receptors with reported housekeeping functions (CXCR3, CXCR4, CXCR5, and CCR6) and to evaluate whether ligands of these receptors play a role in chondrocyte phenotype modulation and proliferation. Methods. Chemokine receptor expression was determined by flow cytometry. Subcultures of chondrocytes were collected and fixed at confluence or during the exponential phase of growth and analyzed for chemokine receptor modulation. The effects of chemokines on isolated cells as well as chondrocytes cultured within an intact extracellular matrix were investigated. Isolated human chondrocytes were stimulated with 100 nM chemokines (monokine induced by interferon-γ, stromal cell-derived factor 1α [SDF-1α], B cell-attracting chemokine 1 [BCA-1], or macrophage inflammatory protein 3α), and conditioned media were assessed for matrix-degrading enzyme contents (matrix metalloproteinases [MMPs] 1, 3, and 13, and N-acetyl-α-D-glucosaminidase [NAG]). Cell proliferation and phenotype modulation were evaluated by bromodeoxyuridine incorporation and cathepsin B production. Induction of cell proliferation was assessed in cartilage explants by immunodetection of the proliferation-associated antigen S100A4. Results. CXCR3, CXCR4, CXCR5, and CCR6 were detected on human chondrocytes. CXCR3 and CXCR4 expression was increased in exponentially growing chondrocyte subcultures. Ligands of all receptors enhanced the release of MMPs 1, 3, and 13. Release of NAG and cathepsin B was significantly higher in chemokine-stimulated cultures than in unstimulated cultures. SDF-1α and BCA-1 also induced DNA synthesis and chondrocyte proliferation, as was shown by the up-regulation of S100A4 in cartilage explants as well. Conclusion. Our findings extend the repertoire of functional responses elicited by the activity of chemokines on chondrocytes and open new avenues in our understanding of the control of chondrocyte differentiation status by chemokines and their receptors.

Original languageEnglish
Pages (from-to)112-122
Number of pages11
JournalArthritis and Rheumatism
Volume50
Issue number1
DOIs
Publication statusPublished - Jan 2004

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Chondrocytes
Chemokines
Phenotype
Chemokine Receptors
Matrix Metalloproteinase 13
Chemokine CXCL12
Hexosaminidases
Matrix Metalloproteinase 3
Cathepsin B
Matrix Metalloproteinase 1
Cartilage
B-Lymphocytes
Cell Proliferation
Monokines
Ligands
Macrophage Inflammatory Proteins
Housekeeping
Bromodeoxyuridine
Conditioned Culture Medium
Interferons

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

A Role for Chemokines in the Induction of Chondrocyte Phenotype Modulation. / Mazzetti, Ilaria; Magagnoli, Giorgia; Paoletti, Samantha; Uguccioni, Mariagrazia; Olivotto, Eleonora; Vitellozzi, Roberta; Cattini, Luca; Facchini, Andrea; Borzì, Rosa Maria.

In: Arthritis and Rheumatism, Vol. 50, No. 1, 01.2004, p. 112-122.

Research output: Contribution to journalArticle

Mazzetti, I, Magagnoli, G, Paoletti, S, Uguccioni, M, Olivotto, E, Vitellozzi, R, Cattini, L, Facchini, A & Borzì, RM 2004, 'A Role for Chemokines in the Induction of Chondrocyte Phenotype Modulation', Arthritis and Rheumatism, vol. 50, no. 1, pp. 112-122. https://doi.org/10.1002/art.11474
Mazzetti I, Magagnoli G, Paoletti S, Uguccioni M, Olivotto E, Vitellozzi R et al. A Role for Chemokines in the Induction of Chondrocyte Phenotype Modulation. Arthritis and Rheumatism. 2004 Jan;50(1):112-122. https://doi.org/10.1002/art.11474
Mazzetti, Ilaria ; Magagnoli, Giorgia ; Paoletti, Samantha ; Uguccioni, Mariagrazia ; Olivotto, Eleonora ; Vitellozzi, Roberta ; Cattini, Luca ; Facchini, Andrea ; Borzì, Rosa Maria. / A Role for Chemokines in the Induction of Chondrocyte Phenotype Modulation. In: Arthritis and Rheumatism. 2004 ; Vol. 50, No. 1. pp. 112-122.
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