Macrolide-based molecules drive bone regeneration

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Macrolide-based molecules drive bone regeneration

Researchers have found that a non-antibiotic derivative of erythromycin could help regenerate bone lost to age-related periodontitis, potentially leading to new treatments for bone loss disorders. (Image: alexisdc/Shutterstock)

NIIGATA, Japan/PHILADELPHIA, US: Ageing is known to increase people’s susceptibility to chronic inflammatory bone loss disorders, including periodontal disease. However, researchers from Niigata University and the University of Pennsylvania have recently found that a non-antibiotic derivative of the macrolide class of antibiotics may help regenerate bone that has been lost as a result of age-related periodontitis. Their work may contribute to the development of novel therapeutic agents for the treatment of bone loss disorders.

“The motivation behind this study is rooted in the understanding that the prevalence of tooth loss due to periodontal disease and fractures in our super-ageing society significantly diminishes the quality of life,” co-researcher Prof. Tomoki Maekawa, who works at the Center for Advanced Oral Science at Niigata University, said in a press release.

Development endothelial locus-1 (DEL-1) is an extracellular matrix protein that helps to reduce inflammation and repair tissue. However, its production declines with age, thus affecting bone regeneration and new bone formation capabilities in the elderly. The researchers had previously monitored DEL-1 expression in the periodontal tissue of mice of different ages and observed that DEL-1 expression gradually reduces with advancing age. In the present study, they demonstrated that locally injecting a special form of DEL-1 in the gingiva of ageing mice significantly improved their bone regeneration.

They then administered macrolides, such as erythromycin, and its non-antibiotic derivative EM-523 to 18-month-old mice and monitored their DEL-1 levels. This restored DEL-1 levels in treated mice and thus promoted the regeneration of bone that was lost due to naturally occurring age-related periodontitis.

The findings indicate that using macrolides and specifically the macrolide-derived compound EM-523 to target DEL-1 expression might be an effective strategy for encouraging bone regeneration in older people. Since EM-523 has non-antibiotic properties, the researchers believe that it may offer fewer adverse reactions and could additionally help prevent antimicrobial resistance.

“The use of drugs with established safety profiles can lead to the early development of an effective bone regeneration agent. We are hopeful that macrolide-based molecules can be developed further as a treatment option for periodontitis,” Prof. Maekawa concluded.

The study, titled “A novel macrolide–Del-1 axis to regenerate bone in old age”, was published online on 16 February 2024 in iScience.

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