Anethole inhibits RANKL-induced osteoclastogenesis by downregulating ERK/AKT signaling and prevents ovariectomy-induced bone loss in vivo
| Autor: | Cong Wang, Hao Qu, Yuankang Zhang, Rongxin He, Nong Lin |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
Ovariectomy Immunology Allylbenzene Derivatives Anisoles Bone resorption chemistry.chemical_compound Mice Osteoclast Bone Density Osteogenesis medicine Immunology and Allergy Animals Humans Bone Resorption Extracellular Signal-Regulated MAP Kinases Anethole Pharmacology Cathepsin Glycogen Synthase Kinase 3 beta Osteoblasts biology Receptor Activator of Nuclear Factor-kappa B Chemistry NF-kappa B Osteoblast Cell Differentiation Resorption Mice Inbred C57BL medicine.anatomical_structure RAW 264.7 Cells RANKL Ovariectomized rat Cancer research biology.protein Osteoporosis Female Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | International immunopharmacology. 100 |
| ISSN: | 1878-1705 |
| Popis: | Postmenopausal osteoporosis is a chronic population health hazard systemic metabolic disease caused by excessive bone resorption and reduced bone formation. The activity between osteoblast and osteoclast, with their mutual effects, influence the procedure of normal bone remodeling. Over-activated osteoclast differentiation and function play a crucial role in excessive bone resorption. Hence, therapy strategies targeting osteoclast activity may promote the bone mass preservation and delay the osteoporosis process. Natural compound (anethole) is emerging as potential therapeutics for various metabolic diseases. The purpose of this study is to investigate the potential effects of anethole on RANKL-induced osteoclast formation and function in vitro and in vivo. Here, in vitro TRAP staining assay was performed to investigate the inhibitory effect of anethole on osteoclast differentiation. Bone pits resorption assay revealed that osteoclast-mediated bone resorption was inhibited by anethole. At mRNA and protein levels, anethole significantly reduced the expression of osteoclast-specific genes expression in a concentration- or time-dependent manner, including NFATc1, MMP-9, DC-STAMP, c-F, TRAP, CTR, Cathepsin K, and V-ATPase d2. Furthermore, intracellular signaling transduction assay indicated that anethole inhibited osteoclast formation via blocking ERK and AKT signaling. GSK3β, the downstream signal of AKT, is simultaneously suppressed with anethole treatment. Based on ovariectomized (OVX) mice model, micro-CT and histological staining results suggested that anethole prevented estrogen deficiency-induced bone mass loss and increased osteoclast activity in vivo. In conclusion, our results show significant indications that anethole exhibits an osteoprotective effect and may be potential for the treatment of osteoporosis. |
| Databáze: | OpenAIRE |
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