Study finds novel macrolide–DEL-1 axis drives bone regeneration in aging individuals (Erythromycin rebuilds bone in older people)

Medical Xpress / Niigata University / iScience ^ | Jan. 25, 2024 | Kridtapat Sirisereephap et al

[ConservativeMind]

Researchers have identified a novel macrolide–DEL-1 axis that helps in bone regeneration and new bone formation. This finding may lead to the development of therapeutic agents to treat bone loss disorders.

Periodontitis is a serious gum infection that damages the soft tissue and destroys the bone that supports teeth. It is usually the result of poor oral hygiene that leads to bacterial infections. Aging may increase susceptibility to periodontitis by altering immune and regenerative functions.

Development endothelial locus-1 (DEL-1), crucial for inflammation resolution and tissue repair, declines with age. The low levels of DEL-1 protein also affect bone regeneration and new bone formation capabilities in the elderly.

Their study highlights the ability of erythromycin to stimulate DEL-1 expression, promoting bone regeneration in aging mice. The non-antibiotic derivative EM-523 reproduces these effects. Mechanistically, macrolide treatments enhance bone formation and reduce osteoclasts, suggesting a potential therapeutic avenue for periodontitis-induced bone loss in humans, especially the elderly.

The research team observed a decline in DEL-1 expression with age and found that 12-month-old mice exhibited reduced bone regeneration compared to younger mice. Local microinjections of recombinant DEL-1-Fc in the gingiva of older mice rescued the bone regeneration deficiency.

Next, the team administered macrolides antibiotics, particularly erythromycin and its non-antibiotic derivative, EM-523, to 18-month-old "aged" mice and monitored the DEL-1 levels. Interestingly, DEL-1 levels were restored in treated mice and the increased levels of DEL-1 promoted the regeneration of bone that was lost due to naturally occurring age-related periodontitis.

Further in-depth studies demonstrated the promising role of DEL-1, indicating new bone formation in the jaws and related gum tissues through increased alkaline phosphatase activity and osteogenic gene expression. These studies also revealed that macrolides influenced inflammation resolution and reduced osteoclastogenesis in a DEL-1-dependent manner.

[ConservativeMind]

The non-antibiotic version is not available, but the antibiotic has been around for a long time.

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