Curcumin reduces the cytotoxicity and osteogenesis inhibition induced by oxidative stress via inhibited the NF-κB and MAPK signaling

// Qihua Qi 1, 2, * , Liangping Li 3, * , Ze min Ling 1, 2 , Yan Chen 1, 2 , Junxuan Ma 2 , Wei Guo 1, 2 , Manman Gao 1, 2 , Zhiyu Zhou 2 , R. Geoff Richards 4 and Xuenong Zou 1, 2 1 Department of Spine Surgery, Orthopedic Research Institute, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China 2 Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China 3 Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, 310016, China 4 AO Research Institute Davos, Davos, 7270, Switzerland * These authors contributed equally to this work Correspondence to: Xuenong Zou, email: zxnong@hotmail.com Keywords: oxidative stress; osteogenesis; reactive oxygen species; curcumin; bone fusion Received: October 30, 2017      Accepted: December 05, 2017      Published: January 02, 2018 ABSTRACT Excessive oxidative stress is considered a significant pathogenic factor leading to the failure of bony fusion at the interface between implanted materials and the host. Curcumin has demonstrated anti-inflammatory and antioxidant properties. However, there were few studies investigating the effects of curcumin on osteogenesis, as well as the underlying mechanism involved in pre-osteoblastic MC3T3-E1 cells. We established an oxidative damage model by exposing MC3T3-E1 cells to hydrogen peroxide (H 2 O 2 ) for 24 h before osteogenic induction with curcumin. We discovered that oxidative stress diminished the viability of MC3T3-E1 cells, inhibited alkaline phosphatase (ALP) activity and calcium mineralization, and down-regulated osteogenesis-related gene expression; low concentrations of curcumin (1–10 μM) reversed the effects of oxidative stress during osteogenic induction, but high concentrations (20 μM) did not. Notably, curcumin exerted its protective effects in part by inhibiting the phosphorylation of JNK and p38 induced by H 2 O 2 and by blocking of the NF-κB signaling pathway. In vivo analysis indicated that curcumin alleviated the deterioration of the micro-architecture of trabecular bone and the reduction in bone mineral density (BMD) of the distal femur; the protective effects of curcumin were dose-dependent. Taken together, these results indicate that curcumin can exert protective effects on osteogenesis and bone remodeling via inhibition of the NF-κB and MAPK pathways. This study suggests that curcumin might be effective in preventing oxidative stress and facilitate osteogenesis.