Related Experiment Video

Updated: Jul 28, 2025

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

13.3K

AMPK negatively regulates RANKL-induced osteoclast differentiation by controlling oxidative stress

Miori Tanaka1, Hirofumi Inoue2, Nobuyuki Takahashi2

  • 1Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan; The Nippon Foundation Human Milk Bank, 17-10 Nihonbashi-koamicho, Chuo-ku, Tokyo, 103-0016, Japan.

Free Radical Biology & Medicine
|June 3, 2023
PubMed

Insights

AMP-activated protein kinase (AMPK) regulates bone metabolism by inhibiting osteoclast differentiation through antioxidant pathways. Activating AMPK with phytochemicals may treat bone diseases by reducing bone resorption.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolism

Background:

  • AMP-activated protein kinase (AMPK) is a key cellular energy sensor involved in metabolic regulation.
  • AMPK deficiency is linked to increased osteoclast numbers and reduced bone mass, but the underlying mechanisms are not fully understood.

Purpose of the Study:

  • To elucidate the mechanistic link between AMPK and osteoclast differentiation.
  • To investigate the role of AMPK in the bone-protective effects of phytochemicals.

Main Methods:

  • Utilized siRNA to knockdown AMPK expression in cells undergoing osteoclast differentiation.
  • Assessed the impact of AMPK knockdown on osteoclastogenesis, gene expression, and signaling pathways (MAPK, NF-κB).
  • Evaluated the effects of antioxidant treatment (N-acetyl-l-cysteine) and phytochemicals (hesperetin, gallic acid, resveratrol, curcumin) on osteoclast differentiation.

Main Results:

  • AMPK knockdown promoted RANKL-induced osteoclast differentiation and activation of MAPK and NF-κB signaling.
  • AMPK deficiency impaired the synthesis of heme oxygenase-1 and Nrf2, crucial components of the antioxidant defense system.
  • Antioxidant treatment and phytochemicals activating AMPK suppressed osteoclast differentiation and associated signaling pathways.

Conclusions:

  • AMPK inhibits osteoclast differentiation by bolstering the antioxidant defense system and managing oxidative stress.
  • AMPK activation through dietary phytochemicals presents a potential therapeutic strategy for bone diseases characterized by excessive bone resorption.
Keywords:
AMPKCell-fusionHO-1OsteoclastOxidative stressPhytochemicals

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