A novel macrolide–Del-1 axis to regenerate bone in old age

Kridtapat Sirisereephap, Hikaru Tamura, Jong Hyung Lim, Meircurius Dwi Condro Surboyo, Toshihito Isono, Takumi Hiyoshi, Andrea L. Rosenkranz, Yurie Sato-Yamada, Hisanori Domon, Akari Ikeda, Tomoyasu Hirose, Toshiaki Sunazuka, Nagako Yoshiba, Hiroyuki Okada, Yutaka Terao, Takeyasu Maeda, Koichi Tabeta, Triantafyllos Chavakis, George Hajishengallis, Tomoki Maekawa

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Aging is associated with increased susceptibility to chronic inflammatory bone loss disorders, such as periodontitis, in large part due to the impaired regenerative potential of aging tissues. DEL-1 exerts osteogenic activity and promotes bone regeneration. However, DEL-1 expression declines with age. Here we show that systemically administered macrolide antibiotics and a non-antibiotic erythromycin derivative, EM-523, restore DEL-1 expression in 18-month-old (“aged”) mice while promoting regeneration of bone lost due to naturally occurring age-related periodontitis. These compounds failed to induce bone regeneration in age-matched DEL-1-deficient mice. Consequently, these drugs promoted DEL-1-dependent functions, including alkaline phosphatase activity and osteogenic gene expression in the periodontal tissue while inhibiting osteoclastogenesis, leading to net bone growth. Macrolide-treated aged mice exhibited increased skeletal bone mass, suggesting that this treatment may be pertinent to systemic bone loss disorders. In conclusion, we identified a macrolide–DEL-1 axis that can regenerate bone lost due to aging-related disease.

Original languageEnglish
Article number108798
JournaliScience
Volume27
Issue number2
DOIs
Publication statusPublished - 16 Feb 2024

Keywords

  • Age
  • Immunology
  • Small molecule

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