A role for chemokines in the induction of chondrocyte phenotype modulation
Samantha Paoletti
Istituto di Ricerca in Biomedicina, Bellinzona, Switzerland
Search for more papers by this authorMariagrazia Uguccioni
Istituto di Ricerca in Biomedicina, Bellinzona, Switzerland
Search for more papers by this authorAndrea Facchini
Istituti Ortopedici Rizzoli, Bologna, Italy, and Università degli Studi di Bologna, Bologna, Italy
Search for more papers by this authorCorresponding Author
Rosa Maria Borzì
Istituti Ortopedici Rizzoli, Bologna, Italy
Laboratorio di Immunologia e Genetica, Istituto di Ricerca Codivilla Putti, Istituti Ortopedici Rizzoli, Via di Barbiano 1/10, Bologna 40136, ItalySearch for more papers by this authorSamantha Paoletti
Istituto di Ricerca in Biomedicina, Bellinzona, Switzerland
Search for more papers by this authorMariagrazia Uguccioni
Istituto di Ricerca in Biomedicina, Bellinzona, Switzerland
Search for more papers by this authorAndrea Facchini
Istituti Ortopedici Rizzoli, Bologna, Italy, and Università degli Studi di Bologna, Bologna, Italy
Search for more papers by this authorCorresponding Author
Rosa Maria Borzì
Istituti Ortopedici Rizzoli, Bologna, Italy
Laboratorio di Immunologia e Genetica, Istituto di Ricerca Codivilla Putti, Istituti Ortopedici Rizzoli, Via di Barbiano 1/10, Bologna 40136, ItalySearch for more papers by this authorAbstract
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-β-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.
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