The key royal jelly component 10-hydroxy-2-decenoic acid protects against bone loss by inhibiting NF-κB signaling downstream of FFAR4

J Biol Chem. 2020 Aug 21;295(34):12224-12232. doi: 10.1074/jbc.RA120.013821. Epub 2020 Jul 9.


The supplementation of royal jelly (RJ) is known to provide a variety of health benefits, including anti-inflammatory and anti-obesity effects. RJ treatment also reportedly protects against bone loss, but no single factor in RJ has yet been identified as an anti-osteoporosis agent. Here we fractionated RJ and identified 10-hydroxy-2-decenoic acid (10H2DA) as a key component involved in inhibiting osteoclastogenesis based on mass spectrometric analysis. We further demonstrated free fatty acid receptor 4 (FFAR4) as directly interacting with 10H2DA; binding of 10H2DA to FFAR4 on osteoclasts inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced activation of NF-κB signaling, thereby attenuating the induction of nuclear factor of activated T cells (NFAT) c1, a key transcription factor for osteoclastogenesis. Oral administration of 10H2DA attenuated bone resorption in ovariectomized mice. These results suggest a potential therapeutic approach of targeting osteoclast differentiation by the supplementation of RJ, and specifically 10H2DA, in cases of pathological bone loss such as occur in postmenopausal osteoporosis.

Keywords: 10-hydroxy-2-decenoic acid; NF-κB (NF-κB); bone; fatty acid; free fatty acid receptor 4 (FFAR4); osteoclast; osteoporosis; royal jelly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Disease Models, Animal
  • Fatty Acids / chemistry*
  • Fatty Acids, Monounsaturated / chemistry
  • Fatty Acids, Monounsaturated / pharmacology*
  • Female
  • Mice
  • NF-kappa B / metabolism*
  • NFATC Transcription Factors / metabolism
  • Osteoclasts / metabolism*
  • Osteoclasts / pathology
  • Osteoporosis / drug therapy*
  • Osteoporosis / metabolism
  • Osteoporosis / pathology
  • RANK Ligand / metabolism
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects*


  • FFAR4 protein, mouse
  • Fatty Acids
  • Fatty Acids, Monounsaturated
  • NF-kappa B
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • RANK Ligand
  • Receptors, G-Protein-Coupled
  • Tnfsf11 protein, mouse
  • 10-hydroxy-2-decenoic acid
  • royal jelly