Abstract
Postmenopausal osteoporosis is caused by an imbalance between osteoclasts and osteoblasts and causes severe bone loss. Osteoporotic medicines are classified into bone resorption inhibitors and bone formation promoters according to the mechanism of action. Long-term use of bisphosphonate and selective estrogen receptor modulators (SERMs) can cause severe side effects in postmenopausal osteoporosis patients. Therefore, it is important to find alternative natural products that reduce osteoclast activity and increase osteoblast formation. Sparganii Rhizoma (SR) is the dried tuberous rhizome of Sparganium stoloniferum Buchanan-Hamilton and is called “samreung” in Korea. However, to date, the effect of SR on osteoclast differentiation and the ovariectomized (OVX)-induced bone loss model has not been reported. In vitro, tartrate-resistant acid phosphatase (TRAP) staining, western blots, RT-PCR and other methods were used to examine the effect of SR on osteoclast differentiation and osteoblasts. In vivo, we confirmed the effect of SR in a model of OVX-induced postmenopausal osteoporosis. SR inhibited osteoclast differentiation and decreased the expression of TNF receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells 1 (NFATc1) and c-Fos pathway. In addition, SR stimulates osteoblast differentiation and increased protein expression of the bone morphogenetic protein 2 (BMP-2)/SMAD signaling pathway. Moreover, SR protected against bone loss in OVX-induced rats. Our results appear to advance our knowledge of SR and successfully demonstrate its potential role as a osteoclastogenesis-inhibiting and osteogenesis-promoting herbal medicine for the treatment of postmenopausal osteoporosis.
Highlights
Bone remodeling is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts (Matsuo and Irie, 2008)
RAW 264.7 cells were treated with receptor activator of nuclear factor-κB ligand (RANKL) (100 ng/ml) and Sparganii Rhizoma (SR) (125, 250, 500, 1,000 μg/ml) for 5 days, and the viability of osteoclasts was not affected after SR treatment
These results indicate that the osteoclast inhibitory effect of SR is not due to toxicity (Figures 1A,B)
Summary
Bone remodeling is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts (Matsuo and Irie, 2008). Bone metabolic diseases such as osteoporosis and Paget’s disease occur when bone formation is reduced due to a decrease in the activity of osteoblasts. Excessive activity of osteoclasts is increased or when the two factors act at the same time (Feng and McDonald, 2011). Osteoporosis is known to be associated with several factors (menopause and aging), and it is characterized by excessive bone loss, weakening of bone microstructure and increased risk of fracture (Sozen et al, 2017). For the treatment of osteoporosis, bone resorption inhibitors such as bisphosphonate and selective estrogen receptor modulators (SERMs) are mainly used (Kennel and Drake, 2009; Gu et al, 2016). The discovery of alternative natural products that decrease osteoclast activity and increase osteoblast formation with fewer side effects than the current medications is crucial
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