Gallic acid inhibits osteoclastogenesis and prevents ovariectomy-induced bone loss

Front Endocrinol (Lausanne). 2022 Dec 19:13:963237. doi: 10.3389/fendo.2022.963237. eCollection 2022.

Abstract

Osteoporosis is a common metabolic bone disease with a rapidly increasing prevalence, characterized by massive bone loss because of excessive osteoclast formation. Gallic acid (GA), a phenolic acid isolated from Cornus officinalis, has anti-inflammatory and anti-oxidant effects, but its effect on osteoclast formation has not been confirmed. In our study, we demonstrated that GA significantly inhibited RANKL-induced osteoclast formation and function of osteoclast in bone marrow monocytes (BMMs) and RAW264.7 cells in a dose-dependent manner without cytotoxicity. For molecular mechanisms, GA repressed osteoclastogenesis by blocking Akt, ERK, and JNK pathways, and suppressed osteoclastogenesis-related marker expression, including nuclear factor of the activated T-cell cytoplasmic 1 (NFATc1), c-Fos, and cathepsin K (CTSK). In addition, we further assessed the effect of GA in an ovariectomized mouse model, which indicated that GA has a notable effect on preventing bone loss. In conclusion, GA exerts notable effects in inhibiting osteoclastogenesis and preventing ovariectomy-induced bone loss, suggesting that GA is a potential agent in osteoporosis treatment.

Keywords: Akt; ERK; Gallic acid; JNK; osteoclast; osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Gallic Acid / pharmacology
  • Gallic Acid / therapeutic use
  • Humans
  • Mice
  • NFATC Transcription Factors / metabolism
  • Osteogenesis*
  • Osteoporosis* / drug therapy
  • Osteoporosis* / etiology
  • Osteoporosis* / prevention & control
  • Ovariectomy / adverse effects

Substances

  • Gallic Acid
  • NFATC Transcription Factors