Inflammation, a common situation during the process of bone healing, is reported to play a negative role in bone regeneration. Up to date, therapeutic strategies for inflammation triggered inhibition of osteoblast differentiation are still limited. The aim of this study was to explore the potential roles and molecular mechanisms of Herbacetin in the process of osteoblast differentiation under LPS-mediated inflammatory environment. By using MC3T3-E1, C2C12 and primary mouse calvarial osteoblast (PMCO) cells as experimental models, we observed that LPS stimulation suppressed osteoblast differentiation via inhibiting alkaline phosphatase (ALP) activity and the expression of several osteoblastic genes (osterix, runx2 and osteocalcin). However, the negative role of LPS during osteoblast differentiation could be restored by Herbacetin treatment. Mechanistical studies revealed that Herbacetin treatment suppressed AKT activation and in turn blocked NF-κB signaling pathway. Furthermore, reactivating AKT by a selective PTEN inhibitor SF1670 suppressed the effect of Herbacetin. These data suggested that Herbacetin might play a protective role in osteoblast differentiation in MC3T3-E1/C2C12/PMCO cells under LPS stimulation.
Keywords: AKT/NF-κB; Herbacetin; LPS; osteoblast differentiation.