Sesamin Protects the Femoral Head From Osteonecrosis by Inhibiting ROS-Induced Osteoblast Apoptosis in Rat Model.

Shuang Deng,Jian-Lin Zhou,Hong-Song Fang,Zhi-Gang Nie,Sen Chen,Hao Peng

doi:10.3389/fphys.2018.01787

Shuang Deng, Jian-Lin Zhou + Show 4 more

Open Access

https://doi.org/10.3389/fphys.2018.01787

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Abstract

Glucocorticoids intake has become the most common pathogenic factor for osteonecrosis of the femoral head (ONFH). Annually, tens of millions of patients suffer from pain related to ONFH. Researchers have proposed several underlying mechanisms of ONFH, including osteocyte apoptosis, cell differentiation disorder, and angiogenesis hindrance. Sesamin, isolated from Sesamum indicum seeds, was reported could affect osteocyte inflammation and differentiation in osteoarthritis and osteoporosis. We investigated the underlying influence of sesamin on ONFH rat model. Fifteen male Sprague-Dawley rats were randomly divided into three groups. The ONFH model group only received the methylprednisolone (MPS) and lipopolysaccharide (LPS) injection to promote the development of ONFH. The sesamin treatment group was injected with sesamin, MPS, and LPS. The control group was untreated. Rats from above groups were sacrificed 4 weeks later. The effect of sesamin on ONFH rats was validated by H&E staining. TUNEL staining showed that femoral head necrosis was attenuated by sesamin. Furthermore, the phosphorylation of Akt was increased and the downstream cellular apoptosis signal pathway was inhibited. Intracellular ROS level was decreased after sesamin treatment. In conclusion, our findings suggest that sesamin protects the femoral head from osteonecrosis by inhibiting ROS-induced osteoblast apoptosis.

Highlights

20,000–30,000 patients in the United States are diagnosed as osteonecrosis of the femoral head (ONFH) annually (Moya-Angeler et al, 2015)
Osteonecrosis of the femoral head has become a common disease with a high disability rate
Apoptotic signals transduced through the PI3K/Akt-Bax/Bcl-2/caspase 3 pathway has been reported in some orthopedic diseases (Li et al, 2012, 2015; Sato et al, 2015)

Summary

INTRODUCTION

20,000–30,000 patients in the United States are diagnosed as ONFH annually (Moya-Angeler et al, 2015). Sesamin Inhibits ROS-Induced Osteonecrosis alters inflammation in GC-induced animal models, leading to side effects including ONFH (Beck et al, 2009). Sesamin was reported to have various anti-cancer functions, including protecting cells from oxidative stress, reducing tumor cell proliferation, inhibiting inflammatory processes, and stimulating cellular apoptosis (Nakano et al, 2003; Hou et al, 2004; Fujikawa et al, 2005; Banjerdpongchai et al, 2010; Chung et al, 2010). We investigated the function of sesamin in an ONFH rat model and primary osteoblasts. Experiments using primary osteoblasts indicated that Dex activated cellular apoptosis, which was reversed by sesamin, possibly by decreasing ROS expression. Our study is the first functional investigation of sesamin in ONFH, and provides a wider perspective for disease treatment

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