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| Item Type: | Article |
|---|---|
| Title: | Mitochondrial respiratory chain function promotes extracellular matrix integrity in cartilage |
| Creators Name: | Bubb, K., Holzer, T., Nolte, J.L., Krüger, M., Wilson, R., Schlötzer-Schrehardt, U., Brinckmann, J., Altmüller, J., Aszodi, A., Fleischhauer, L., Clausen-Schaumann, H., Probst, K. and Brachvogel, B. |
| Abstract: | Energy metabolism and extracellular matrix function together orchestrate and maintain tissue organization, but crosstalk between these processes is poorly understood. Here, we used single cell RNA-seq (scRNA-seq) analysis to uncover the importance of the mitochondrial respiratory chain for extracellular matrix homeostasis in mature cartilage. This tissue produces large amounts of a specialized extracellular matrix to promote skeletal growth during development and maintain mobility throughout life. A combined approach of high-resolution scRNA-seq, mass spectrometry/matrisome analysis, and atomic force microscopy was applied to mutant mice with cartilage-specific inactivation of respiratory chain function. This genetic inhibition in cartilage results in the expansion of a central area of 1-month-old mouse femur head cartilage, showing disorganized chondrocytes and increased deposition of extracellular matrix material. scRNA-seq analysis identified a cell cluster-specific decrease in mitochondrial DNA-encoded respiratory chain genes and a unique regulation of extracellular matrix-related genes in nonarticular chondrocytes. These changes were associated with alterations in extracellular matrix composition, a shift in collagen/non-collagen protein content, and an increase of collagen crosslinking and ECM stiffness. These results demonstrate that mitochondrial respiratory chain dysfunction is a key factor that can promote ECM integrity and mechanostability in cartilage and presumably also in many other tissues. |
| Keywords: | Atomic Force Microscopy, Extracellular Matrix, MMP10, Matrisome, Matrix Metalloproteinase, Mitochondria, Mitochondrial Respiratory Chain, Single Cell RNA-Seq, THBS1, Transcriptomics, Animals, Mice |
| Source: | Journal of Biological Chemistry |
| ISSN: | 1083-351X |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Volume: | 297 |
| Number: | 4 |
| Page Range: | 101224 |
| Date: | October 2021 |
| Official Publication: | https://doi.org/10.1016/j.jbc.2021.101224 |
| PubMed: | View item in PubMed |
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