M1 Bent Brachvogel, Julia Etich
Mitochondrial dysfunction in cartilage and its consequences for ECM and joint homeostasis
University Hospital for Pediatrics and Adolescent Medicine
Experimental Neonatology
Faculty of Medicine, University of Cologne
Joseph-Stelzmann-Str. 52, 50931 Cologne
Dr. Julia Etich
Klinik und Poliklinik für Kinder- und Jugendmedizin
Experimentelle Neonatologie
Medizinische Fakultät, Universität zu Köln
Joseph-Stelzmann-Str. 52, 50931 Köln
Summary
The integrity of cartilage is warranted by the interaction of chondrocytes with their surrounding extracellular matrix (ECM), but during aging this interplay deteriorates. Mitochondria should act as substantial factor for chondrocyte homeostasis and ECM production, secretion and degradation and recent descriptive studies link mitochondrial dysfunction to pathological cartilage degeneration. We could show that mitochondrial dysfunction in cartilage disturbs the ECM composition leading to premature growth plate closure, dystrophic bone formation and impaired joint integrity. Within the research unit we now want to understand the molecular mechanisms by which mitochondrial dysfunction affect cartilage/ECM homeostasis and joint integrity. Consequences on cartilage and bone organization, inflammation and the metabolism will be determined and the link between mitochondrial dysfunction and aging-related degenerative cartilage diseases will be studied. This project will provide an understanding of the role of mitochondria for ECM production and remodeling, cartilage to bone transformation and the pathogenesis of mitochondria-related joint diseases.Publications
Georgieva VS, Etich J, Bluhm B, Zhu M, Frie C, Wilson R, Zaucke F, Bateman J, Brachvogel B 2020 Ablation of the miRNA Cluster 24 Has Profound Effects on Extracellular Matrix Protein Abundance in Cartilage. Int J Mol Sci 21(11):E4112.
Heilig J, Dietmar H, Brachvogel B, Paulsson M, Zaucke F, Niehoff A 2020 Collagen IX deficiency causes premature vascularization and ossification of murine femoral heads through an imbalance of pro- and antiangiogenic factors. Osteoarthritis Cartilage 28(7):988-999.
Etich J, Koch M, Wagener R, Zaucke F, Fabri M, Brachvogel B 2019 Gene Expression Profiling of the Extracellular Matrix Signature in Macrophages of Different Activation Status: Relevance for Skin Wound Healing. Int J Mol Sci 20(20).
Holzer T, Probst K, Etich J, Auler M, Georgieva VS, Bluhm B, Frie C, Heilig J, Niehoff A, Nüchel J, Plomann M, Seeger JM, Kashkar H, Baris OR, Wiesner RJ, Brachvogel B 2019 Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases. J Cell Biol 218(6):1853-1870.
Üstün Y, Reibetanz M, Brachvogel B, Nischt R, Eckes B, Zigrino P, Krieg T 2019 Dual role of laminin‑511 in regulating melanocyte migration and differentiation. Matrix Biol 80:59-71.
Weiland D, Brachvogel B, Hornig-Do HT, Neuhaus JFG, Holzer T, Tobin DJ, Niessen CM, Wiesner RJ, Baris OR 2018 Imbalance of Mitochondrial Respiratory Chain Complexes in the Epidermis Induces Severe Skin Inflammation. J Invest Dermatol 138(1):132-140.
Bergmeier V, Etich J, Pitzler L, Frie C, Koch M, Fischer M, Rappl G, Abken H, Tomasek JJ, Brachvogel B 2017 Identification of a myofibroblast-specific expression signature in skin wounds. Matrix Biol Aug 7. pii: S0945-053X(17)30084-7.
Bluhm B, Ehlen HWA, Holzer T, Georgieva VS, Heilig J, Pitzler L, Etich J, Bortecen T, Frie C, Probst K, Niehoff A, Belluoccio D, Van den Bergen J, Brachvogel B 2017 miR-322 stabilizes MEK1 expression to inhibit RAF/MEK/ERK pathway activation in cartilage. Development 144(19):3562-35771.
Etich J, Holzer T, Pitzler L, Bluhm B, Brachvogel B 2015 MiR-26a modulates extracellular matrix homeostasis in cartilage. Matrix Biol 43:27-34.
Wilson R, Norris EL, Brachvogel B, Angelucci C, Zivkovic S, Gordon L, Bernardo BC, Stermann J, Sekiguchi K, Gorman JJ, Bateman JF 2012 Changes in the chondrocyte and extracellular matrix proteome during post-natal mouse cartilage development. Mol Cell Proteomics 11(1):M111 014159.
Belluoccio D, Etich J, Rosenbaum S, Frie C, Grskovic I, Stermann J, Ehlen H, Vogel S, Zaucke F, von der Mark K, Bateman JF, Brachvogel B 2010 Sorting of growth plate chondrocytes allows the isolation and characterization of cells of a defined differentiation status. J Bone Miner Res 25(6):1267-1281.
Belluoccio D, Grskovic I, Niehoff A, Schlotzer-Schrehardt U, Rosenbaum S, Etich J, Frie C, Pausch F, Moss SE, Poschl E, Bateman JF, Brachvogel B 2010 Deficiency of annexins A5 and A6 induces complex changes in the transcriptome of growth plate cartilage but does not inhibit the induction of mineralization. J Bone Miner Res 25(1):141-153.
