10-Gingerol Suppresses Osteoclastogenesis in RAW264.7 Cells and Zebrafish Osteoporotic Scales

• Published in: Frontiers in cell and developmental biology Vol. 9; p. 588093
• Main Authors: Zang, Liqing, Kagotani, Kazuhiro, Nakayama, Hiroko, Bhagat, Jacky, Fujimoto, Yuki, Hayashi, Akihito, Sono, Ryoji, Katsuzaki, Hirotaka, Nishimura, Norihiro, Shimada, Yasuhito
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 03-03-2021
• Subjects: bone regeneration; bone resorption; Cell and Developmental Biology; Danio rerio; natural product; osteopenia; osteopenia; bone regeneration; natural product; Danio rerio; bone resorption
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2021.588093

Osteoporosis is the most common aging-associated bone disease and is caused by hyperactivation of osteoclastic activity. We previously reported that the hexane extract of ginger rhizome [ginger hexane extract (GHE)] could suppress receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells. However, the anti-osteoclastic components in GHE have not yet been identified. In this study, we separated GHE into several fractions using silica gel column chromatography and evaluated their effects on osteoclastogenesis using a RAW264.7 cell osteoclast differentiation assay (
) and the zebrafish scale model of osteoporosis (
). We identified that the fractions containing 10-gingerol suppressed osteoclastogenesis in RAW264.7 cells detected by tartrate-resistant acid phosphatase (TRAP) staining. In zebrafish, GHE and 10-gingerol suppressed osteoclastogenesis in prednisolone-induced osteoporosis regenerated scales to promote normal regeneration. Gene expression analysis revealed that 10-gingerol suppressed osteoclast markers in RAW264.7 cells [osteoclast-associated immunoglobulin-like receptor, dendrocyte-expressed seven transmembrane protein, and matrix metallopeptidase-9 (
)] and zebrafish scales [osteoclast-specific cathepsin K (CTSK),
, and
]. Interestingly, nuclear factor of activated T-cells cytoplasmic 1, a master transcription regulator of osteoclast differentiation upstream of the osteoclastic activators, was downregulated in zebrafish scales but showed no alteration in RAW264.7 cells. In addition, 10-gingerol inhibited CTSK activity under cell-free conditions. This is the first study, to our knowledge, that has found that 10-gingerol in GHE could suppress osteoclastic activity in both
and
conditions.