Funktion der cGMP/PKGI Signalkaskade während der Osteogenese, und in Krankheitsmodellen
Zusammenfassung der Projektergebnisse
Cyclic guanosine monophosphat (cGMP) mediates physiological effects of nitric oxide and natriuretic peptides on different processes in whole body, including bone formation and ossification. Osteoporotic bone loss, the most common metabolic bone disease affecting humans, is becoming major problem due to increasing ageing population. Novel therapies for osteoporosis are needed and cGMP modulating substances could be an interesting approach to treat osteoporosis. Using osteogenic cell models and knockout mice, we recently demonstrated involvement of PKGII in bone development. In addition, PKGII initiates proliferative responses in mechanically stimulated osteoblast. Our data in mesenchymal stem cells and primary osteoblasts showed high expression of PKGI. Deletion of PKGI in primary osteoblasts showed a trend towards lower osteogenic marker mRNA expression for alkaline phosphatase (ALP) in vitro. Furthermore, BMP-induced gene osteoblast differentiation was enhanced with cGMP treatment suggesting a PKGI- dependent mechanism.
