Longitudinal monitoring of in vitro remodeling

Stefan Remmers

The maintenance of bone is regulated by formation and resorption processes mediated by osteoblasts and osteoclasts respectively. Imbalances in these processes are responsible for skeletal diseases such as osteoporosis. Most therapies act on this formation/resorption equilibrium and slow the progression of osteoporosis. However, we do not understand the physiology and pathophysiology of bone well enough to be able to cure osteoporosis, and the disease remains degenerative in nature. In order to study bone physiology and pathophysiology in more detail, we will design a model system capable of mimicking bone remodeling in vitro. The simplest model system for bone remodeling should have human osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells) in co-culture on mineralized 3D constructs, that can be monitored non-destructively over time to determine when and how mineralized bone matrix remodels in response to biochemical or physical stimuli. Monitoring of the mineralized matrix structure and its deposition and degradation can be established using micro-computed tomography (µCT), a fast and non-destructive 3D imaging technique. Other non-destructive techniques will be employed to further aid in elucidating bone resorption and formation processes over time. After culture, destructive techniques such as histology and qPCR will be used to provide more information. The model will be validated using known drugs, and can be used to study the effect of applied biochemical and physical stimuli on bone formation and resorption. Such a model will hopefully aid in both fundamental research on bone physiology and diseases and in testing medication against such diseases.

This project is supported by the "Seventh Framework Programme" (FP/2007-2013) / EU Project No. 336043