The implication of the notch signaling pathway in biphasic calcium phosphate ceramic‐induced ectopic bone formation: A preliminary experiment

Abstract

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.

Study on the difference of osteogenesis and Notch signaling pathway expression in biphasic calcium‐phosphorus ceramic granule materials with different microstructure

“…Studies have suggested that up‐regulation of the Notch signaling pathway promoted differentiation of BMSCs and significantly enhanced early bone formation 14 . When co‐culturing Sprague–Dawley (SD) rat BMSCs and BCP material, a significant up‐regulation in the expression of the Notch signaling pathway was detected in our previous study 15 . We found that the expression level of Notch1was up‐regulated about 30‐fold on the 1st, 4th, and 7th days of co‐culture (in vitro), meanwhile the overall expression levels of osteogenic genes were also up‐regulated.…”

“…14 When co-culturing Sprague-Dawley (SD) rat BMSCs and BCP material, a significant up-regulation in the expression of the Notch signaling pathway was detected in our previous study. 15 We found that the expression level of Notch1was up-regulated about 30-fold on the 1st, 4th, and 7th days of co-culture (in vitro), meanwhile the overall expression levels of osteogenic genes were also up-regulated. Subsequently, after the addition of the Notch pathway inhibitor (RO4929097), the up-regulation was significantly inhibited, giving the conclusion that BCP can promote differentiation of BSMCs by upregulating the Notch signaling pathway and contributing to early osteogenesis.…”

“…In this study, nine 1‐year‐old beagle dogs (12–14 kg, male and female) were anesthetized with Sutai (0.5 ~ 0.55 mg/kg), atropine (1 ml), and dormicin (0.5 ml), placed prone on the table 15 . An incision about 8 cm‐10 cm long was made in the middle of their back.…”

“…In this study, nine 1-year-old beagle dogs (12-14 kg, male and female) were anesthetized with Sutai (0.5 ~0.55 mg/kg), atropine (1 ml), and dormicin (0.5 ml), placed prone on the table. 15 An incision about 8 cm-10 cm long was made in the middle of their back. The intramuscular pockets with a diameter of 2 cm and a depth of 3 cm were obtusely separated in the dorsal muscle.…”

Cryogenic 3D Printing of ß-TCP/PLGA Composite Scaffolds Incorporated With BpV (Pic) for Treating Early Avascular Necrosis of Femoral Head

“…In the last decade, scaffold-based bone tissue engineering has gained increasing attention in various orthopaedic applications ( Sadiasa et al, 2013 ; Tao et al, 2019 ; Guo et al, 2020 ). It is a key scientific issue to prevent and cure ANFH by implanting bioactive materials combined with biologically active factors of key regulatory pathways ( Sharma et al, 2019 ).…”