Suppressive effects of 1,4-dihydroxy-2-naphthoic acid administration on bone resorption

Masakazu Matsubara, Eiki Yamachika, H. Tsujigiwa, N. Mizukawa, T. Ueno, Jun Murakami, Nobuhisa Ishida, Y. Kaneda, N. Shirasu, S. Takagi

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


The main component of the metabolic by-products of fermentation by Propionibacterium freudenreichii ET-3 is 1,4-dihydroxy-2-naphthoic acid (DHNA), which has a naphthoquinone skeleton, as in vitamin K2. This study showed that DHNA improved bone mass reduction with osteoporosis model mice caused by FK506. Introduction: Growth of the intestinal bacterium Lactobacillus bifidus is specifically facilitated by DHNA. The present study used osteoporosis model mice to investigate the effects of DHNA on bone remodeling. Methods: FK506, an immunosuppressant, was used to prepare osteoporosis model mice. Thirty mice were divided into three groups: FK group, FK+DHNA group, and control group. In the FK group, FK506 was administered to induce bone mass reduction. In the FK-DHNA group, FK506 and DHNA were administered concurrently to observe improvements in bone mass reduction. To ascertain systemic and local effects of DHNA, we investigated systemic pathological changes in colon, kidney function and cytokine dynamics, and morphological and organic changes in bone and osteoclast dynamics as assessed by culture experiments. Results: Compared to the FK group without DHNA, colon damage and kidney dysfunction were milder for FK+DHNA group, and production of inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α) was more suppressed. Furthermore, compared to the group without DHNA, histological analyses and radiography showed that bone resorption was suppressed for the DHNA group. Culture experiments using osteoclasts from murine bone marrow showed osteoclast suppression for the DHNA group compared to the group without DHNA. Conclusion: These results show that DHNA has some effects for improving bone mass reduction caused by FK506.

Original languageEnglish
Pages (from-to)1437-1447
Number of pages11
JournalOsteoporosis International
Issue number8
Publication statusPublished - Aug 2010


  • Bone metabolism
  • Bone resorption
  • DHNA
  • FK506
  • Osteoporosis
  • Osteoporosis treatment

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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