Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Hydroxychavicol Inhibits In Vitro Osteoclastogenesis via the Suppression of NF-κB Signaling Pathway

  • Sirada Srihirun (Department of Pharmacology, Faculty of Dentistry, Mahidol University) ;
  • Satarat Mathithiphark (Faculty of Allied Health Sciences, Burapha University) ;
  • Chareerut Phruksaniyom (Department of Pharmacology, Faculty of Dentistry, Mahidol University) ;
  • Pitchanun Kongphanich (Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Wisutthaporn Inthanop (Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Thanaporn Sriwantana (Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Salunya Tancharoen (Department of Pharmacology, Faculty of Dentistry, Mahidol University) ;
  • Nathawut Sibmooh (Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Pornpun Vivithanaporn (Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University)
  • Received : 2023.03.27
  • Accepted : 2023.07.31
  • Published : 2024.03.01
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Abstract

Hydroxychavicol, a primary active phenolic compound of betel leaves, previously inhibited bone loss in vivo by stimulating osteogenesis. However, the effect of hydroxychavicol on bone remodeling induced by osteoclasts is unknown. In this study, the anti-osteoclastogenic effects of hydroxychavicol and its mechanism were investigated in receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclasts. Hydroxychavicol reduced the number of tartrate resistance acid phosphatase (TRAP)-positive multinucleated, F-actin ring formation and bone-resorbing activity of osteoclasts differentiated from RAW264.7 cells in a concentration-dependent manner. Furthermore, hydroxychavicol decreased the expression of osteoclast-specific genes, including cathepsin K, MMP-9, and dendritic cell-specific transmembrane protein (DC-STAMP). For mechanistic studies, hydroxychavicol suppressed RANKL-induced expression of major transcription factors, including the nuclear factor of activated T-cells 1 (NFATc1), c-Fos, and c-Jun. At the early stage of osteoclast differentiation, hydroxychavicol blocked the phosphorylation of NF-κB subunits (p65 and Iκβα). This blockade led to the decrease of nuclear translocation of p65 induced by RANKL. In addition, the anti-osteoclastogenic effect of hydroxychavicol was confirmed by the inhibition of TRAP-positive multinucleated differentiation from human peripheral mononuclear cells (PBMCs). In conclusion, hydroxychavicol inhibits osteoclastogenesis by abrogating RANKL-induced NFATc1 expression by suppressing the NF-κB signaling pathway in vitro.

Keywords

Acknowledgement

This research study is supported by Specific League Funds from Mahidol University and Dean's Research Novice Award of the Faculty of Medicine Ramathibodi Hospital, Mahidol University. We acknowledge the facilities and technical assistance of the Research office, Faculty of Dentistry, Mahidol University. We would like to thank Mr. Sarut Thairat for his technical assistance for confocal microscopy.

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