Bent Brachvogel

FM | Experimental Neonatology (UHC)

Prof. Dr. Bent Brachvogel CECAD Cologne
Prof. Dr. Bent Brachvogel

Principal Investigator

Research Areas

1
3

Metabolism-Matrix Crosstalk in Skeletal Growth & Aging

With aging people experience joint stiffening, cartilage and bone degeneration. Early perturbations in the metabolism-matrix crosstalk can accelerate these aging processes and cause degenerative joint diseases.

Research Focus

The extracellular matrix is a dynamic bioactive network which connects muscle, cartilage and bone to coordinate musculoskeletal development. Many of these matrix structures are maintained throughout life, very often under metabolically challenging conditions. We unraveled the overall importance of a postnatal metabolic switch from glycolysis to mitochondrial respiration to sustain matrix and joint cartilage integrity. Lack of respiration results in premature cartilage matrix degeneration and growth retardation as it is frequently observed in patients with mitochondrial diseases. We now focus our research on the crosstalk between metabolism and matrix that translates mitochondrial dysfunction into age-related joint diseases.

Our Goals

Our research focusses on early postnatal metabolic perturbations that cause degenerative joint diseases.

  • Specifically, we aim to decipher how cells with defective mitochondria rewire their metabolism and signaling networks to maintain basal cellular function and how these adaptations provoke premature joint cartilage degeneration. We hypothesize that the primarily cellular response against mitochondrial dysfunction, in the long term, disrupts matrix formation and accelerates premature cartilage degeneration leading to mitochondria-related skeletal pathologies.

We aim to define metabolic pathways and regulatory networks that provoke age-related matrix degradation and joint diseases.

  • Moreover, we are pursuing research to understand the reciprocal impact of matrix perturbation on joint cartilage metabolism and mitochondria function and we aim to model related human diseases using an iPSC/organoid technology platform. This technology will be employed to provide underpinning mechanistic knowledge of aging and degeneration processes caused by disturbed metabolism-matrix interactions that are specific to the human system and complement our animal models.

Key Publications


  1.  Zhou M, Metzen F, Hopkinson M, Betz J, Heilig J, Sodhi J, Imhof T, Niehoff A, Birk DE, Izu Y, Krüger M, Pitsillides AA, Altmüller J, van Osch GJVM, Straub V,  Schreiber G, Paulsson M, Koch M, Brachvogel B. (2023) Ablation of collagen XII disturbs joint extracellular matrix organization and causes patellar subluxation iSience, 2023 Jun 28;26(7):107225
  2. Bubb, K., Holzer, T., Nolte, J. L., Kruger, M., Wilson, R., Schlotzer-Schrehardt, U., Brinckmann, J., Altmuller, J., Aszodi, A., Fleischhauer, L., Clausen-Schaumann, H., Probst, K., and Brachvogel, B. (2021) Mitochondrial respiratory chain function promotes extracellular matrix integrity in cartilage. J Biol Chem, 101224
  3. Auler, M., Bergmeier, V., Georgieva, V. S., Pitzler, L., Frie, C., Nuchel, J., Eckes, B., Hinz, B., and Brachvogel, B. (2021) miR-127-3p Is an Epigenetic Activator of Myofibroblast Senescence Situated within the MicroRNA-Enriched Dlk1-Dio3Imprinted Domain on Mouse Chromosome 12. J Invest Dermatol141, 1076-1086 e1073
  4. Holzer, T., Probst, K., Etich, J., Auler, M., Georgieva, V. S., Bluhm, B., Frie, C., Heilig, J., Niehoff, A., Nuchel, J., Plomann, M., Seeger, J. M., Kashkar, H., Baris, O. R., Wiesner, R. J., and Brachvogel, B. (2019) Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases. J Cell Biol218, 1853-1870
  5. Bluhm, B., Ehlen, H. W. A., Holzer, T., Georgieva, V. S., Heilig, J., Pitzler, L., Etich, J., Bortecen, T., Frie, C., Probst, K., Niehoff, A., Belluoccio, D., Van den Bergen, J., and Brachvogel, B. (2017) miR-322 stabilizes MEK1 expression to inhibit RAF/MEK/ERK pathway activation in cartilage. Development144, 3562-3577
Prof. Dr. Bent Brachvogel CECAD Cologne
Prof. Dr. Bent Brachvogel

Principal Investigator

Research Areas

1
3