Abstract
The stem of Acer tegmentosum has been widely used in Korea for the treatment of hepatic disorders. In this study, we investigated the bone protective effect of water extract of the stem of Acer tegmentosum (WEAT). We found that WEAT inhibits osteoclast differentiation induced by receptor activator of nuclear factor-κB ligand (RANKL), an essential cytokine for osteoclast differentiation. In osteoclast precursor cells, WEAT inhibited RANKL-induced activation of JNK, NF-κB, and cAMP response element-binding protein, leading to suppression of the induction of c-Fos and nuclear factor of activated T cells cytoplasmic 1, key transcription factors for osteoclast differentiation. In addition, WEAT inhibited bone resorbing activity of mature osteoclasts. Furthermore, the oral administration of WEAT reduced RANKL-induced bone resorption and trabecular bone loss in mice. Taken together, our study demonstrates that WEAT possesses a protective effect on bone destruction by inhibiting osteoclast differentiation and function.
Highlights
Bone is constantly remodeled through the removal of old bone by osteoclasts and the replacement of new bone by osteoblasts
Upon binding of RANKL to RANK expressed on osteoclast precursors, TNF receptor-associated factors are recruited to the intracellular domain of RANK and activate downstream signaling pathways including mitogen-activated protein (MAP) kinases and NF-κB, and cAMP response element-binding protein (CREB), which leads to the induction of osteoclastogenic transcription factors such as c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) [4,5,6,7,8,9,10]
When WEAT was added to the cultures at the same time as RANKL, a dose-dependent inhibition of osteoclast differentiation was observed, with nearly complete inhibition of osteoclast differentiation at 50 μg/mL (Figure 1A,B)
Summary
Bone is constantly remodeled through the removal of old bone by osteoclasts and the replacement of new bone by osteoblasts. The TNF ligand superfamily member, receptor activator of nuclear factor NF-κB ligand (RANKL), which is expressed in cells of osteoblastic lineage and lymphoid tissue, is a pivotal factor for the formation, function, and survival of osteoclasts [2,3]. Previous studies have demonstrated that the RANKL-RANK-OPG axis is important for normal bone remodeling and plays a crucial role in pathological bone destruction [11]. To find medicinal herbs with potential bone protective effects, we investigated the effects of various herbal extracts on RANKL-induced osteoclast differentiation from its precursor cells and found that water extract of the stem of. Previous studies have shown that extracts of the stem of Acer tegmentosum possess various pharmacological properties including anti-inflammatory, anti-gastrophatic, anti-adipogenic, anti-cancer, and anti-oxidant effects [14,15,16,17,18]. Using a murine model of bone destruction by RANKL, its bone protective effect was examined
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