Abstract
Osteoporosis with bone loss is widely recognized as a major health problem. Bone homeostasis is maintained by balancing bone formation and bone resorption. The imbalance caused by increased bone resorption over bone formation can lead to various bone-related diseases such as osteoporosis and rheumatoid arthritis. Osteoclasts are the principal cells responsible for bone resorption and the main targets of anti-resorptive therapies. However, excessive inhibition of osteoclast differentiation may lead to inhibition of osteoblast differentiation. Therefore, it is important to screen for new compounds capable of inhibiting bone resorption and enhancing bone formation. Toddalia asiatica (L.) Lam. has been utilized traditionally for medicinal purposes such as the treatment of rheumatism. Currently, the extract is considered to be a good source of pharmacological agents for the treatment of bone-related diseases, but the active compounds have yet to be identified. We investigated whether toddaculin, derived from Toddalia asiatica (L.) Lam., affects both processes by inhibiting bone resorption and enhancing bone formation. Towards this end, we used pre-osteoclastic RAW 264 cells and pre-osteoblastic MC3T3-E1 cells. We found that toddaculin not only inhibited the differentiation of osteoclasts via activation of the NF-κB, ERK 1/2, and p38 MAPK signaling pathways, but it also induced differentiation and mineralization of osteoblasts by regulating differentiation factors. Thus, toddaculin might be beneficial for the prevention and treatment of osteoporosis.
Highlights
Osteoclasts resorb bone and support normal bone remodeling
In the present study, we investigated whether toddaculin had both effects by in vitro studies of pre-osteoclastic RAW 264 cells and pre-osteoblastic MC3T3-E1 cells
Osteoporosis with bone loss is widely recognized as a major health problem afflicting more than 200 million people worldwide [14, 15]
Summary
Osteoclasts resorb bone and support normal bone remodeling. Osteoclasts are regulated by receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) and macrophage colonystimulating factor (M-CSF) [1]. Since tartrate-resistant acid phosphatase (TRAP) is highly expressed in osteoclasts, TRAP activity is used as a sensitive marker for osteoclasts [2]. Excess osteoclast activity is known to lead to various bone-related diseases such as osteoporosis and rheumatoid arthritis [3]. Osteoblasts stimulate mineralization and bone production by regulating proliferation and differentiation of osteoblast precursors [4]. Alkaline phosphatase (ALP) is highly expressed in osteoblasts, and ALP activity is used as a sensitive marker for osteoblasts [5]
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