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Background: Osteoclasts are the only cell type capable of breaking down bone matrix, and its excessive activation is responsible for the development of bone-destructive diseases.
Euphorbia lathyris L. (ELL) is an herbal plant that belongs to the Euphorbiaceae family. This study investigated the effects of the methanol extract of the aerial part of ELL on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation and signaling pathways. Methods: Osteoclasts were formed by co-culturing mouse bone marrow with osteoblasts or by culturing mouse bone marrow-derived macrophages (BMMs) with macrophage colony-stimulating factor (M-CSF) and RANKL.
Bone resorption assays were performed using dentine slices. The expression level of mRNA was analyzed by real-time polymerase chain reaction (PCR) or reverse transcription (RT)-PCR. Western blotting assays were performed to detect the expression or activation level of proteins. Results: ELL inhibited RANKL-induced osteoclast formation without cytotoxicity. Furthermore, the RANKL-stimulated bone resorption was diminished by ELL. Mechanistically, ELL blocked the RANKL-triggered p38 mitogen-activated protein kinase (MAPK) phosphorylation, which resulted in the suppression of the expression of c-Fos and nuclear factor of activated T cells (NFATc1). In osteoblasts, ELL had little effect on the mRNA expression of RANKL and osteoprotegerin (OPG). Conclusions: The present data suggest that ELL has an inhibitory effect on osteoclast differentiation and function via downregulation of the p38/c-Fos/NFATc1 signaling pathways. Thus, ELL could be useful for the treatment of bone diseases associated with excessive bone resorption.
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참고문헌 (26)
참고문헌 신청
Tanaka Y / 2005 / Osteoblasts and osteoclasts in bone remodeling and inflammation / Curr Drug Targets Inflamm Allergy 4:325~328
Teitelbaum SL / 2000 / Bone resorption by osteoclasts / Science 289:1504~1508
Suda T / 1999 / Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families / Endocr Rev 20:345~357
Boyle WJ / 2003 / Osteoclast differentiation and activation / Nature 423:337~342
Arai F / 1999 / Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB(RANK)receptors / J Exp Med 190:1741~1754
Teitelbaum SL / 2000 / Bone resorption by osteoclasts / Science 289:1504~1508
Suda T / 1999 / Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families / Endocr Rev 20:345~357
Boyle WJ / 2003 / Osteoclast differentiation and activation / Nature 423:337~342
Arai F / 1999 / Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB(RANK)receptors / J Exp Med 190:1741~1754
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