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 where bone formation and bone resorption can be quantified in a reproducible manner.
Monitoring of osteoblast and osteoclast activity can be realized by quantifying ALP and TRAP activity in culture supernatant respectively. After culture, destructive techniques such as a resorption assay, Calcium/ALP/DNA assays, histology and qPCR will be used to provide more information on osteoclastic resorption and osteoblastic mineralization. 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.