Abstract
The aim of this study was to evaluate the effects of root bark of Eleutherococcus sessiliflorus (ES) on osteoclast differentiation and function in vitro and in vivo. In vitro, we found that ES significantly inhibited the RANKL-induced formation of TRAP-positive multinucleated osteoclasts and osteoclastic bone resorption without cytotoxic effects. ES markedly downregulated the expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1); c-Fos; and osteoclast-related marker genes, such as TRAP, osteoclast-associated receptor (OSCAR), matrix metalloproteinase-9 (MMP-9), calcitonin receptor, cathepsin K, the 38 kDa d2 subunit of the vacuolar H+-transporting lysosomal ATPase (Atp6v0d2), dendritic cell-specific transmembrane protein (DC-STAMP), and osteoclast-stimulatory transmembrane protein (OC-STAMP). These effects were achieved by inhibiting the RANKL-mediated activation of MAPK signaling pathway proteins, including p38, ERK, and JNK. In vivo, ES attenuated OVX-induced decrease in bone volume to tissue volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and bone mineral density, but increased trabecular separation (Tb.Sp) in the femur. Collectively, our findings showed that ES inhibited RANKL-activated osteoclast differentiation in bone marrow macrophages and prevented OVX-mediated bone loss in rats. These findings suggest that ES has the potential to be used as a therapeutic agent for bone-related diseases, such as osteoporosis.
Highlights
Osteoporosis is a systemic skeletal disease characterized by a decrease in bone mass and abnormalities in the bone microstructure, resulting in an increased risk of fractures
To examine the effects of Eleutherococcus sessiliflorus (ES) on RANKL-induced osteoclastogenesis, bone marrow macrophages (BMMs) treated with M-CSF and RANKL were cultured in the presence or absence of ES for 4 days
To determine the cytotoxicity of ES, BMMs were treated with various concentrations of ES (12.5, 25, and 50 μg/mL) in the presence of M-CSF, and cell viability was measured by the XTT assay
Summary
Osteoporosis is a systemic skeletal disease characterized by a decrease in bone mass and abnormalities in the bone microstructure, resulting in an increased risk of fractures. It mainly occurs in postmenopausal women and elderly men. The treatment for osteoporosis includes two types of therapies: antiresorptive and anabolic. Antiresorptive drugs primarily reduce bone resorption, while anabolic drugs increase new bone formation. Several therapeutic agents for osteoporosis increase bone mineral density (BMD) and reduce the risk of skeletal fractures; these treatments were reported to have various adverse effects, such as osteonecrosis of the jaw, thrombosis, atypical femur fractures, hypocalcemia, and stroke [3,4,5]
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