Osteologie 2021; 30(04): 335-336
DOI: 10.1055/s-0041-1736714
Abstract

Single cell RNA sequencing identifies mitochondrial respiration as a key factor contributing to extracellular matrix integrity

K Bubb
1   Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany and Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany
,
T Holzer
1   Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany and Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany
,
J L Nolte
2   Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
,
M Krüger
2   Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
,
R Wilson
3   Central Science Laboratory, University of Tasmania, Hobart, TAS 7005, Australia   ;
,
U Schlötzer-Schrehardt
4   Department of Ophthalmology, University Hospital Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany
,
J Brinckmann
5   Department of Dermatology, Institute of Virology and Cell Biology, University of Lübeck, Lübeck, Germany
,
J Altmüller
6   Cologne Center for Genomics, University of Cologne, Cologne, Germany
,
A Aszodi
7   Department of General, Trauma and Reconstructive Surgery, Munich University Hospital, Ludwig-Maximilians-University, Munich, Germany
,
L Fleischhauer
7   Department of General, Trauma and Reconstructive Surgery, Munich University Hospital, Ludwig-Maximilians-University, Munich, Germany
8   Center for Applied Tissue Engineering and Regenerative Medicine, Munich University of Applied Sciences, Munich, Germany
,
H Clausen-Schaumann
8   Center for Applied Tissue Engineering and Regenerative Medicine, Munich University of Applied Sciences, Munich, Germany
,
K Probst
1   Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany and Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany
,
B Brachvogel
1   Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany and Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany
› Author Affiliations
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Introduction

During endochondral ossification, chondrocytes are in need of constant energy supply to maintain proliferation and matrix deposition. Mitochondrial respiration is one of the major cellular energy source and is described to drive postnatal growth, but the importance for extracellular matrix (ECM) homeostasis is poorly understood.


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Material and Methods

Cartilage morphology of 28 days old mice with a cartilage specific genetic inhibition of the respiratory chain (Col2Cre-Twinkle) was studied by immunological and histological methods. Individual transcriptomes of chondrocytes were analysed by single cell RNA sequencing (scRNA-seq) and proteome analysis was applied to define consequences for ECM composition. Properties of the ECM were characterised by ultrastructural analysis and atomic force microscopy.


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Results

Inactivation of the respiratory chain in chondrocytes results in disorganization and expansion of femoral head cartilage of Col2Cre-Twinkle mice. scRNA-seq analysis demonstrates that mitochondrial DNA encoded genes are specifically decreased in the nonarticular chondrocytes population accompanied by a changed expression of ECM-related genes. Among those thrombospondin-1 and matrilin-1 are accumulated in the enlarged disorganized femur head cartilage of mutant mice. The changes in the ECM are associated with an increase of ECM crosslinks and higher stiffness of mature cartilage.


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Conclusion

The results show that mitochondrial respiration is an important biochemical cue for ECM organisation and mechanostability of mature cartilage.


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Conflict of Interest

All authors declare that they have no conflict of interest.

Publication History

Article published online:
04 November 2021

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