Shikimic Acid Inhibits Osteoclastogenesis in Vivo and in Vitro by Blocking RANK/TRAF6 Association and Suppressing NF-κB and MAPK Signaling Pathways
| Autor: | Longjuan Qin, Xiaoqun Li, Xin Zhi, Jiacan Su, Liehu Cao, Xiao Chen, Xiao Zhai |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Physiology MAP Kinase Signaling System NFATc1 Osteoclasts Shikimic Acid Bone resorption lcsh:Physiology lcsh:Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice Postmenopausal osteoporosis Osteoclast In vivo Osteogenesis medicine Animals lcsh:QD415-436 Viability assay Calcitonin receptor Bone Resorption Cells Cultured Cathepsin TNF Receptor-Associated Factor 6 biology lcsh:QP1-981 Receptor Activator of Nuclear Factor-kappa B Chemistry Acid phosphatase NF-kappa B Cell Differentiation Mesenchymal Stem Cells Shikimic acid Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure RAW 264.7 Cells biology.protein Female Signal Transduction |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 51, Iss 6, Pp 2858-2871 (2018) |
| ISSN: | 1421-9778 |
| Popis: | Background/Aims: Bone homeostasis is associated with the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Unbalanced bone homeostasis as a result of reduced osteogenesis or excessive osteoclastogenesis can lead to disorders such as osteoporosis, Paget’s disease, and rheumatoid arthritis. Shikimic acid is a cyclohexanecarboxylic acid, reported to exhibit pharmacological properties including anti-inflammatory and antioxidant activities. However, its effects on bone homeostasis remain unknown. Methods: First, the in vitro MTT cell viability assay was performed. Tartrate-resistant acid phosphatase (TRAP) and actin ring formation assays, as well as immunofluorescence staining were then performed to evaluate osteoclastogenesis. Potential signaling pathways were characterized by western blotting and verified in overexpression experiments. Related factors were examined by western blotting, reverse transcription polymerase chain reaction, electrophoretic mobility shift assay, and co-immunoprecipitation. Ovariectomized mice were used for the in vivo study. Results: TRAP staining showed that shikimic acid significantly inhibited osteoclastogenesis and pit resorption in bone marrow monocytes and RAW264.7 cells, and actin ring formation assays showed that shikimic acid suppressed the bone resorption function of osteoclasts. Furthermore, shikimic acid inhibited the receptor activator of nuclear factor-κB RANK/tumor necrosis factor receptor-associated factor 6 (TRAF6) association, suppressed nuclear factor-κB and mitogen-activated protein kinase signaling pathways, and downregulated nuclear factor of activated T-cell cytoplasmic 1. The expression of osteoclastogenesis biomarkers, including TRAF6, calcitonin receptor, TRAP, cathepsin K, and matrix metalloproteinase-9, was inhibited. In vivo, shikimic acid also significantly ameliorated bone loss and prevented osteoclastogenesis in ovariectomized mice. Conclusion: Shikimic acid inhibited osteoclastogenesis and osteoclast function by blocking RANK ligand-induced recruitment of TRAF6, as well as downstream signaling pathways in vitro. Shikimic acid also reduced ovariectomy-induced osteoclastogenesis and bone loss in vivo. |
| Databáze: | OpenAIRE |
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