Growth-related oncogene α induction of apoptosis in osteoarthritis chondrocytes

Rosa Maria Borzi, Ilaria Mazzetti, Giorgia Magagnoli, Samantha Paoletti, Mariagrazia Uguccioni, Rita Gatti, Guido Orlandini, Luca Cattini, Andrea Facchini

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. To evaluate the apoptotic effect of the chemokine growth-related oncogene α (GROα), which we recently reported to be up-regulated in osteoarthritis (OA) chondrocytes. Chondrocyte apoptosis is considered to be a major determinant of cartilage damage in OA, a disease resulting from the aberrant production of inflammatory mediators (cytokines and chemokines) and effectors (matrix metalloproteinases and reactive oxygen and nitrogen species) by chondrocytes. Methods. We investigated the apoptotic effect of GROα on isolated human cells and on in vitro-cultured cartilage explants by conventional methods (morphology, detection of DNA fragmentation in situ and in solution, exposure of phosphatidylserine) and by analysis of "early" biochemical events (plasma membrane depolarization, activation of caspase 3, and phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase). Results. We clearly demonstrated that GROα was able to initiate a series of morphologic, biochemical, and molecular changes that led to chondrocyte apoptosis. Moreover, we found that additional signals delivered from the extracellular matrix (ECM) were essential in the control of chondrocyte susceptibility to GROαinduced apoptosis, since cell death was detected only when cells were stimulated after reestablishment of their proper interactions with the ECM, or in cartilage explant samples with reduced ECM, as indicated by decreased Safranin O staining. Conclusion. GROα can induce apoptosis in articular chondrocytes, and the induction is dependent upon additional signals from the ECM. These findings are relevant to understanding the pathogenesis of OA, in view of the availability of the GROα chemokine in the joint space in the course of this rheumatic disease.

Original languageEnglish
Pages (from-to)3201-3211
Number of pages11
JournalArthritis and Rheumatism
Volume46
Issue number12
DOIs
Publication statusPublished - Dec 1 2002

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Fingerprint Dive into the research topics of 'Growth-related oncogene α induction of apoptosis in osteoarthritis chondrocytes'. Together they form a unique fingerprint.

Cite this