Chondrocyte hypertrophy and apoptosis induced by GROα require three-dimensional interaction with the extracellular matrix and a co-receptor role of chondroitin sulfate and are associated with the mitochondrial splicing variant of cathepsin B
| العنوان: | Chondrocyte hypertrophy and apoptosis induced by GROα require three-dimensional interaction with the extracellular matrix and a co-receptor role of chondroitin sulfate and are associated with the mitochondrial splicing variant of cathepsin B |
|---|---|
| المؤلفون: | Annalisa Facchini, Sabrina Burattini, Spartaco Santi, Patricia Fernandez, Elisabetta Falcieri, Andrea Facchini, Eleonora Olivotto, Michela Battistelli, Rosa Maria Borzì, Flavio Flamigni, Roberta Vitellozzi |
| المساهمون: | Olivotto E., Vitellozzi R., Fernandez P., Falcieri E., Battistelli M., Burattini S., Facchini A., Flamigni F., Santi S., Borzì R.M. |
| المصدر: | Journal of Cellular Physiology. 210:417-427 |
| بيانات النشر: | Wiley, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Adult, Physiology, Chemokine CXCL1, p38 mitogen-activated protein kinases, Clinical Biochemistry, Apoptosis, Core Binding Factor Alpha 1 Subunit, Chondrocyte hypertrophy, Biology, p38 Mitogen-Activated Protein Kinases, Cathepsin B, Chondrocyte, Mitochondrial Proteins, Extracellular matrix, chemistry.chemical_compound, Chondrocytes, Matrix Metalloproteinase 13, medicine, Humans, Protein Isoforms, Anoikis, Chondroitin sulfate, Cells, Cultured, Aggrecan, Aged, Glycosaminoglycans, Aged, 80 and over, Chondroitin Sulfates, Cell Differentiation, Hypertrophy, Cell Biology, Middle Aged, Extracellular Matrix, Up-Regulation, Cell biology, Enzyme Activation, Alternative Splicing, Cartilage, medicine.anatomical_structure, chemistry, Biochemistry, Chemokines, CXC |
| الوصف: | CXCR2 ligands contribute to chondrocyte hypertrophy and apoptosis, important determinants in cartilage pathophysiology. We unraveled the kinetics of signaling, biochemical, transcriptional, and morphological events triggered by GROα in human osteoarthritic chondrocytes kept in three-dimensional culture. p38 MAPK activation was assessed with a highly sensitive ELISA. Effector caspase activation was evaluated by cleavage of a fluorogenic substrate. Gene expression of key markers of hypertrophy (MMP-13, Runx-2) and matrix synthesis (aggrecan), and of cathepsin B isoform CB(-2,3) was evaluated by real time PCR. Occurrence of the morphological markers of apoptosis was investigated by transmission electron microscopy (TEM). GROα led to p38 MAPK activation in passaged chondrocytes cultured in micromass but not as a high-density monolayer. This caused the downstream triggering of chondrocyte hypertrophy (MMP-13 and Runx-2 upregulation, and calcium deposition) and apoptosis/anoikis following concurrence of matrix degrading activity, and inhibition of matrix synthesis which also involved the induction of CB(-2,3). These phenomena proved to be dependent on the co-receptor role of sulfated glycosaminoglycans (sGAG) and the activation of p38 MAPK, since they were abrogated either by preincubation with soluble chondroitin-4 sulfate or p38 MAPK inhibitors. The co-receptor role of sGAG was further demonstrated by colocalization experiments of these molecules with GROα in the stimulated micromasses. These findings suggest that extracellular matrix exerts a regulatory role in chondrocytes differentiation, and that meaningful investigation of the effects of chemokines on chondrocyte biology requires culture conditions respectful of both the differentiated status of the chondrocytes and of their three-dimensional interaction with the extracellular matrix. J. Cell. Physiol. 210: 417–427, 2007. © 2006 Wiley-Liss, Inc. |
| وصف الملف: | STAMPA |
| تدمد: | 1097-4652 0021-9541 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dcc58548709cdc59214ce40beeb21365Test https://doi.org/10.1002/jcp.20864Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....dcc58548709cdc59214ce40beeb21365 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974652 00219541 |
|---|