| First Author | Sirisereephap K | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 2 | Pages | 108798 |
| PubMed ID | 38261928 | Mgi Jnum | J:351218 |
| Mgi Id | MGI:7578541 | Doi | 10.1016/j.isci.2024.108798 |
| Citation | Sirisereephap K, et al. (2024) A novel macrolide-Del-1 axis to regenerate bone in old age. iScience 27(2):108798 |
| abstractText | 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. |
