Navigation of osteoblasts in the bone space

• Applicant: Philipp Mayer-Kuckuk, Ph.D.
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 276075520

Bone formation, for example during bone growth or remodeling, depends on the capacity of osteoblasts for migration to designated areas of bone formation. Thus, posing the fundamental question: How do osteoblasts navigate to the appropriate position within the bone space? It is known that they attach to the extracellular matrix via integrins and that they can migrate in a chemoattractant-dependent fashion. However, given limited specificity and number of known chemoattractans, it is unlikely that chemotaxis alone permits navigation. Therefore, our underlying hypothesis is that the interplay of biophysical and cellular signals provides coordinates for navigation. We plan on studying the kinetics of primary osteoblasts on the single cell level in real-time. For Aim 1, we hypothesize that osseous surfaces offer basic navigation signals to osteoblasts, while Aim 2 will test the hypothesis that two or three party cell interactions provide additional navigation coordinates for osteoblasts. In Aim 3, we will test if directed, localized fluid flow serves as landmark in osteoblast navigation. Together, these studies are expected to reveal go/stop signals osteoblasts use for navigation. The results will lead to extended studies addressing the pathways controlling such signals. The long term impact of the proposed studies is far-reaching with implications in many aspects of musculoskeletal research, such as bone tissue engineering, metabolic bone disease, and skeletal cancer.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Rainer Burgkart