The role of caspase activation in the regulation of osteoclast fusion and bone homeostasis

• Applicant: Dr. Carina Scherbel, since 10/2022
• Subject Area: Rheumatology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 411374928

Osteoclasts are multinucleated, bone resorbing cells formed via fusion of monocyte progenitors. Increased osteoclast activity is regularly observed during pathologic states such as rheumatoid arthritis and different forms of osteoporosis. Existing studies identified several genes involved in osteoclast fusion but the basic cellular regulatory mechanisms underlying multinucleation of osteoclasts are poorly understood. Recent experiments proposed a role of phosphatidylserine exposure as well as of caspases in osteoclast development, but these two events have not been linked and the mechanisms underlying the pro-osteoclastic effect of caspases as well as pathways leading to phosphatidylserine exposure in osteoclast precursors are not understood. We hypothesize that osteoclast precursors display a controlled and non- apoptotic caspase activation that results in phosphatidylserine exposure and osteoclast precursor fusion without inducing cell death. To identify novel pathways and targets genes involved in osteoclast fusion will help to design novel therapeutic strategies for the treatment of osteoporosis and bone-related diseases.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Gerhard Krönke, from 1/2020 until 10/2022