The implication of the notch signaling pathway in biphasic calcium phosphate ceramic-induced ectopic bone formation:...

Calcium phosphate (BCP) ceramic is a promising material in bone regeneration because it was proved biocompatible, osteoconductive, osteoinductive, and effective. Although it manifests favorable characteristics in critical-sized bone defects repair, the mechanism of its osteoinduction is still unclear. In the present study, we studied the mechanism of ectopic bone formation, with interest in the Notch signaling pathway. BCP ceramics with or without Notch signaling inhibitor RO4929097 were cocultured with bone marrow-derived stem cells in vitro. The expression of osteogenesis (OPN/Col/Runx2) and Notch signaling pathway-related genes (Hes1/Jagged/Notch1) were increased in the BCP group compared with the control group without BCP but significantly decreased after adding RO4929097. Furthermore, a higher level of alkaline phosphatase activity was observed in the BCP group compared with RO4929097 and control group separately. For further confirmation, the intramuscularly ectopic implantation models of Beagle dogs were used. Quantitative real-time polymerase chain reaction showed a similar trend with the in vitro experiment. Histological and histomorphometric analysis indicated that bone formation was delayed by RO4929097. These findings illustrated that the Notch signaling pathway plays a pivotal role in bone formation induced by BCP; Notch signaling pathway may positively influence ectopic bone formation by promoting BMSCs to differentiate toward osteoblasts.