Osteoblasts are specialized cells in our bones which are important for bone mineralization. A team of researchers from DKFZ-Hector Cancer Institute at the University Medical Center Mannheim* and University Medical Center Hamburg Eppendorf identified an enzyme regulating osteoblast activity. They further found that blocking this enzyme using therapeutics led to reduced cancer-induced bone resorption and diminished number of bone metastasis in multiple myeloma as well as lung and breast cancer models.
The team around first author Janik Engelmann, Sonja Loges and Isabel Ben-Batalla identified the two enzymes MERTK und TYRO3, which are both receptor tyrosine kinases important for bone production. Using mice with specific knock-out of one of the two enzymes in their osteoblasts they found that MERTK inactivation led to increased bone mass while TYRO3 deletion in osteoblasts induced bone mass reduction. With this first evidence that MERTK in osteoblasts could contribute to cancer-induced inhibition of bone formation they went on and used R992 to inhibit its activity. They showed that treatment of healthy mice with R992 led to increased number of osteoblasts and higher bone mass. Mouse models of multiple myeloma, lung or breast cancer showed decreased bone loss and reduced number of bone metastasis, too. Since R992 is not approved as drug yet, Sonja Loges and her team currently work on the development of an antibody against MERTK to be able to investigate the effect of MERTK inhibition in patients as well.
We are proud to present this new publication of our µBone researchers Sonja Loges & Isabel Ben-Batalla (Project 2) together with Klaus Pantel (Project 18) and Hanna Taipaleenmäki & Eric Hesse (Project 11) in Nature Communications. First author Janik Engelmann was the recipient of a µBone clinician-scientist fellowship.
Enjoy the read: Janik Engelmann, Jennifer Zarrer, Victoria Gensch, Kristoffer Riecken, Nikolaus Berenbrok, The Vinh Luu Antonia Beitzen-Heineke, Maria Elena Vargas-Delgado, Klaus Pantel, Carsten Bokemeyer, Somasekhar Bhamidipati, Ihab S. Darwish, Esteban Masuda, Tal Burstyn-Cohen, Emily J. Alberto, Sourav Ghosh, Carla Rothlin, Eric Hesse, Hanna Taipaleenmäki, Isabel Ben-Batalla, Sonja Loges. Regulation of bone homeostasis by Mertk and TYRO3. Nat Commun. 2022 Dec 12;13(1):7689. doi: 10.1038/s41467-022-33938-x.
* The DKFZ-Hector-Cancer Center at the University Medical Center Mannheim is a cooperation of the German Cancer Center (DKFZ), the Medical Faculty of Mannheim of the University of Heidelberg and the University Hospital Mannheim.