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

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.
Yosuke Tsuchiya 1,  Mikihito Hayashi 2,  Katashi Nagamatsu 3,  Takehito Ono 4,  Masaki Kamakura 5,  Takanori Iwata 6,  Tomoki Nakashima 7
Affiliations

Affiliations

  • 1 Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
  • 2 Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Agency for Medical Research and Development, Precursory Research for Innovative Medical Care (PRIME), Tokyo, Japan.
  • 3 R&D Division, MORIKAWA KENKODO CO., LTD., Kumamoto, Japan.
  • 4 Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan.
  • 5 Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, Toyama, Japan.
  • 6 Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
  • 7 Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan. Electronic address: naka.csi@tmd.ac.jp.
PMID: 32647011 DOI: 10.1074/jbc.RA120.013821
Abstract

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.

Figures
Products