Emodin promotes the osteogenesis of MC3T3-E1 cells via BMP-9/Smad pathway and exerts a preventive effect in ovariectomized rats

Xiaojing Chen, Shuang Zhang, Xiaoting Chen, Yan Hu, Jin Wu, Shuyan Chen, Jing Chang, Genfa Wang, and Yanhong Gao

Department of Geriatrics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China

Acta Biochim Biophys Sin 2017, 49: 867–878; doi: 10.1093/abbs/gmx087

Emodin, a natural anthraquinone extracted from the Chinese herbs rhubarb and giant knotweed rhizome, has been reported to enhance osteoblast differentiation. However, the mechanisms underlying its ability to regulate osteogenesis are unclear. The objective of this study was to determine the role of emodin in osteoblast function in vitro and its osteoprotective effect in vivo. Emodin enhanced the differentiation and mineralization of MC3T3-E1 cells, as evidenced by elevated alkaline phosphatase activity and increased number of mineralized nodules. In cultured osteoblasts, emodin significantly induced the mRNA expression of BMP-9 which is one of the least studied but most osteogenic bone morphogenetic proteins (BMPs). Furthermore, the bone morphogenetic protein receptor-Smad (BMPR-Smad) signaling axis and p38 mitogen activated protein kinase (p38 MAPK) were activated. The in vivo function of emodin were evaluated by assessing bone histomorphology, trabecular bone microarchitecture, mechanical properties of the skeleton, and serum parameters of bone turnover in ovariectomized (OVX) rats. Emodin combined with low-dose of estrogen improved trabecular bone microarchitecture in the fourth lumbar vertebra compared with low-dose estrogen alone and enhanced vertebral body strength. Moreover, emodin suppressed the OVX-induced elevation of serum osteocalcin (OC). In addition, there were fewer side effects on uterine hypertrophy with the combination therapy than with high-dose estrogen alone. However, emodin alone did not exert any osteoprotective effect. These results suggest that emodin may be a promising alternative agent for osteoporosis in combination therapy.

HE-stained histological sections of tibia

 Three-dimensional reconstruction of trabecular bone

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