Journal
BONE
Volume 74, Issue -, Pages 18-28Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2015.01.002
Keywords
Ophiopogonin D; Reactive oxygen species; Osteoclastogenesis; Osteogenesis; FoxO3a; beta-Catenin
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Funding
- Ministry of Science and Technology of the People's Republic of China [2011CB964703]
- National Natural High Technology Research and Development Program 863 [2012AA020502]
- National Natural Science Foundation of China [81400859]
- Program for Changjiang Scholars and Innovative Research Team in University [IRT13053]
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Excessive reactive oxygen species (ROS) play an important role in the development of osteoporosis. Ophiopogonin D (OP-D), isolated from the traditional Chinese herbal agent Radix Ophiopogon japonicus, is a potent anti-oxidative agent. We hypothesized that OP-D demonstrates anti-osteoporosis effects via decreasing ROS generation in mouse pre-osteoblast cell line MC3T3-E1 subclone 4 cells and a macrophage cell line RAW264.7 cells. We investigated OP-D on osteogenic and osteoclastic differentiation under oxidative status. Hydrogen peroxide (H2O2) was used to establish an oxidative damage model. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Then, we searched the molecular mechanism of OP-D against osteoporosis. Our results revealed that OP-D significantly promoted the proliferation of MC3T3-E1 cells and improved some osteogenic markers. Moreover, OP-D reduced TRAP activity and the mRNA expressions of osteoclastic genes in RAW264.7 cells. OP-D suppressed ROS generation in both MC3T3-E1 and RAW264.7 cells. OP-D treatment reduced the activity of serum bone degradation markers, including CTX-1 and TRAP. Further research showed that OP-D displayed anti-osteoporosis effects via reducing ROS through the FoxO3a-beta-catenin signaling pathway. In summary, our results indicated that the protective effects of OP-D against osteoporosis are linked to a reduction in oxidative stress via the FoxO3a-beta-catenin signaling pathway, suggesting that OP-D may be a beneficial herbal agent in bone-related disorders, such as osteoporosis. (C) 2015 Elsevier Inc. All rights reserved.
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