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Biology of bone regeneration – Franziska Knopf

Bone fractures in humans heal well, especially at young age. Unfortunately, bone is not replaced after severe injury or upon long term treatment with certain drugs. In order to better understand mechanisms of successful versus impaired bone regeneration, we make use of highly regenerative zebrafish, and evaluate their bone forming capacity in different experimental contexts.

 

 

 

 

Fig.: Zebrafish caudal fin (left). Gene expression in the early regenerating fin (right).

Previous and current research

Although bone is a regenerative tissue also in humans, it can be permanently lost in circumstances of trauma, cancer or degenerative diseases. Due to their high regenerative capacity zebrafish have emerged as a powerful tool to study bone regeneration. In particular, bone forming and bone degrading cells (osteoblasts and osteoclasts) can be visualized easily in zebrafish, thus allowing their observation in the living organism. This can be used to monitor osteoblast and osteoclast function throughout processes of bone formation and bone degradation, and to study cross-talk of bone cells with other types of cells, such as immune cells, in the bone niche.

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Future projects and goals

Our overall research goal is to unravel the mechanisms underlying bone formation with a view to exploit the regenerative capabilities of zebrafish. In particular, we investigate cellular and molecular mechanisms of succesful versus impaired bone regeneration in the zebrafish fin and skull, and take advantage of the zebrafish model to study the pathogenesis of different forms of bone fragility.

Selected publications

Geurtzen, K., Vernet, A., Freidin, A., Rauner, M., Hofbauer, L.C., Schneider, J.E., Brand, M., Knopf, F. Immune suppressive and bone inhibitory effects of prednisolone in growing and regenerating zebrafish tissues. Journal of Bone and Mineral Research 2017 (in press); doi 10.1002/jbmr.3231.

Masselink, W., Cole, N., Berger, S., Fenyes, F., Sonntag, C., Wood, A., Nguyen, P.D., Cohen, N., Knopf, F., Weidinger, G., Hall, T.E., & Currie, P.D. (2016). A somitic contribution to the apical ectodermal ridge is essential for fin formation. Nature 535 (7613): 542-546.

Antos, C.L., Knopf, F., and Brand, M. Regeneration of organs and appendages in zebrafish: A window into underlying control mechanisms. In: Encyclopedia of Life Sciences, John Wiley & Sons, Ltd: Chichester http://www.els.net/A26051.

Geurtzen, K.*, Knopf, F*., Wehner, D. Huitema, L.F., Schulte-Merker, S. and Weidinger, G. (2014). Mature osteoblasts dedifferentiate in response to traumatic bone injury in the zebrafish fin and skull. Development 141: 2225-2234. * equal contribution.

Knopf, F., Hammond, C., Chekuru, A., Kurth, T., Hans, S., Weber, C.W., Mahatma, G., Fisher, S., Brand, M., Schulte-Merker, S., and Weidinger, G. (2011). Bone regenerates via dedifferentiation of osteoblasts in the zebrafish fin. Developmental Cell 20:713-724.

Knopf, F.*, Schnabel, K.*, Haase, C., Pfeifer, K., Anastassiadis, K., and Weidinger, G. (2010). Dually inducible TetON systems for tissue-specific conditional gene expression in zebrafish. Proceedings of the National Academy of Sciences 107 (46):19933-8. * equal contribution.

Group members

Contact

Group Leader

Dr. Franziska Knopf

Assistant to Group Leader

Anke Weber