Caffeic Acid Inhibits RANKL and TNFa-induced Osteoclastogenesis by Targeting TAK1-p44/42 MAPK
Abstract
BACKGROUND: The potential of the caffeic acid in other important Receptor Activator Nuclear Factor kB Ligand (RANKL)-Tumor Necrosis Factor (TNF)a-induced osteoclastogenic signaling pathways has not been known. Therefore, the current study was conducted to explore as well as to understand the inhibition potential of caffeic acid.
METHODS: RAW264.7 cells were cultured, treated with caffeic acid, RANKL and TNFa. Tartrate Resistant Acid Phosphatase (TRAP) staining was performed to detect TRAP+ osteoclast-like polynuclear cells. To detect the activity of p44/42 Mitogen Activated Protein Kinase (MAPK), Akt, and Transforming Growth Factor-β-activated Kinase (TAK)1, the phosphorylated forms of the proteins were investigated with the immunoblotting assay.
RESULTS: Pre-treatment of caffeic acid inhibited the RANKL and TNFa-induced differentiation of RAW264.7 cells into TRAP+ osteoclast-like polynuclear cells. RANKL and TNFa induced phosphorylation of p44/42 MAPK at Thr202/Tyr204, phosphorylation of Akt at both Ser473 and Thr308 and phosphorylation of TAK1 at Ser412. Pre-treatment with caffeic acid prior to the RANKL and TNFa induction, inhibited the phosphorylation of MAPK, and TAK1, but not Akt.
CONCLUSION: Caffeic acid might regulate the RANKL-TNFa-induced osteoclastogenic pathway in RAW264.7 by targeting TAK1, which later activation of p44/42 MAPK was abolished.
KEYWORDS: caffeic acid, osteoclastogenesis, p44/42, Erk1/2, Akt, TAK1, RAW264.7
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Toh K, Kukita T, Wu Z , Kukita A, Sandra F, Tang QY, et al. Possible involvement of MIP-1α in the recruitment of osteoclast progenitors to the distal tibia in rats with adjuvant-induced arthritis. Lab Invest. 2004; 84: 1092-102, CrossRef.
Ketherin, Sandra F. Osteoclastogenesis in periodontitis: signaling pathway, synthetic and natural inhibitors. Mol Cell Biomed Sci. 2018; 2: 11-8, CrossRef.
Sandra F, Kukita T, Muta T, Iijima T. Caffeic acid inhibited receptor activator of nuclear factor kappaB ligand (RANKL)-tumor necrosis factor (TNF) alpha-TNF receptor associated factor (TRAF) 6 induced osteoclastogenesis pathway. Indones Biomed J. 2013; 5: 173-8, CrossRef.
Chawalitpong S, Sornkaew N, Suksamrarn A, Palaga T. Diarylheptanoid from Curcuma comosa Roxb. suppresses RANKL-induced osteoclast differentiation by decreasing NFATc1 and c-Fos expression via MAPK pathway. Eur J Pharmacol. 2016; 788: 351-9, CrossRef.
Sandra F, Ketherin K. Caffeic Acid Inhibits RANKL and TNF-α-induced phosphorylation of p38 mitogen-activated protein kinase in RAW-D cells. Indones Biomed J. 2018; 10: 140-3, CrossRef.
Sandra F, Briskila J, Ketherin. RANKL and TNF-a-induced JNK/SAPK osteoclastogenic signaling pathway was inhibited by caffeic acid in RAW-D cells. Indones J Cancer Chemoprevent. 2018; 9: 63-7, CrossRef.
Sandra F, Kukita T, Tang QY, Iijima T. Caffeic acid inhibits NFκB activation of osteoclastogenesis signaling pathway. Indones Biomed J. 2011; 3: 216-22, CrossRef.
Bishop RT, Marino S, Carrasco G, Li B, Allen RJ, Sparatore A, et al. Combined administration of a small-molecule inhibitor of TRAF6 and docetaxel reduces breast cancer skeletal metastasis and osteolysis. Cancer Lett. 2020; 488: 27-39, CrossRef.
Makeudom A, Supanchart C, Montreekachon P, Khongkhunthian S, Sastraruji T, Krisanaprakornkit J, et al. The antimicrobial peptide, human β-defensin-1, potentiates in vitro osteoclastogenesis via activation of the p44/42 mitogen-activated protein kinases. Peptides. 2017; 95: 33-9, CrossRef.
Matsumoto M, Sudo T, Saito T, Osada H, Tsujimoto M. Involvement of p38 mitogen-activated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of NF-kappa B ligand (RANKL). J Biol Chem. 2000; 275: 31155-61, CrossRef.
Yamanaka Y, Clohisy JCF, Ito H, Matsuno T, Abu-Amer Y. Blockade of JNK and NFAT pathways attenuates orthopedic particle-stimulated osteoclastogenesis of human osteoclast precursors and murine calvarial osteolysis. J Orthop Res. 2013; 31: 67-72, CrossRef.
Ren LR, Wang H, He XQ, Song MG, Chen XQ, Xu YQ. Staphylococcus aureus protein A induces osteoclastogenesis via the NF‑κB signaling pathway. Mol Med Rep. 2017; 16: 6020-8, CrossRef.
Meng J, Zhang W, Wang C, Zhang W, Zhou C, Jiang G, et al. Catalpol suppresses osteoclastogenesis and attenuates osteoclast-derived bone resorption by modulating PTEN activity. Biochem Pharmacol. 2020; 171: 113715, CrossRef.
Tang QY, Kukita T, Ushijima Y, Kukita A, Nagata K, Sandra F, et al. Regulation of osteoclastogenesis by Simon extracts composed of caffeic acid and related compounds: successful suppression of bone destruction accompanied with adjuvant-induced arthritis in rats. Histochem Cell Biol. 2006; 125: 215-25, CrossRef.
Sandra F, Sidharta MA. Caffeic acid induced apoptosis in MG63 osteosarcoma cells through activation of caspases. Mol Cell Biomed Sci. 2017; 1: 28-33, CrossRef.
Sandra F, Hudono KF, Putri AA, Putri CAP. Caspase inhibitor diminishes caffeic acid-induced apoptosis in osteosarcoma. Indones Biomed J. 2017; 9: 160-4, CrossRef.
Kim HH, Chung WJ, Lee SW, Chung PJ, You JW, Kwon HJ, et al. Association of sustained ERK activity with integrin beta3 induction during receptor activator of nuclear factor kappaB ligand (RANKL)‐directed osteoclast differentiation. Exp Cell Res. 2003; 289: 368‐377, CrossRef.
Moon JB, Kim JH, Kim K, Youn BU, Ko A, Lee SY, et al. Akt induces osteoclast differentiation through regulating the GSK3β/NFATc1 signaling cascade. J Immunol. 2012; 188: 163-9, CrossRef.
Mizukami J, Takaesu G, Akatsuka H, Sakurai H, Ninomiya-Tsuji J, Matsumoto K, et al. Receptor activator of NF-κB Ligand (RANKL) activates TAK1 mitogen-activated protein kinase kinase kinase through a signaling complex containing RANK, TAB2, and TRAF6. Mol Cell Biol. 2002; 22: 992-1000, CrossRef.
Kobayashi Y, Mizoguchi T, Take I, Kurihara S, Udagawa N, Takahashi N. Prostaglandin E2 enhances osteoclastic differentiation of precursor cells through protein kinase A-dependent phosphorylation of TAK1. J Biol Chem. 2005; 280: 11395-403, CrossRef.
He Y, Staser K, Rhodes SD, Liu Y, Wu X, Park SJ, et al. Erk1 positively regulates osteoclast differentiation and bone resorptive activity. PLoS One. 2011; 6: e24780, CrossRef.
Park JH, Lee NK, Lee SY. Current Understanding of RANK Signaling in Osteoclast Differentiation and Maturation. Mol Cells. 2017; 40: 706-13, CrossRef.
DOI: https://doi.org/10.18585/inabj.v13i4.1593
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