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Polysacharide of Agaricus blazei gel mitigates bone necrosis in model of the jaws related to bisphosphonate via Wnt signaling

Summary

This study tested whether a gel made from Agaricus blazei mushroom could help repair jaw bone damage caused by bisphosphonate medications (used to treat bone loss). Using a rat model, researchers found that the mushroom gel significantly improved bone healing by activating biological pathways that promote bone-forming cell growth and activity. The treatment increased the number of living bone cells, improved bone quality, and reduced bone death and tissue damage. These promising results suggest the mushroom extract could become a helpful treatment to prevent or manage jawbone damage in patients taking bisphosphonate medications.

Background

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe condition affecting jaw bone tissue, particularly following tooth extraction in patients receiving bisphosphonate therapy. The pathophysiology involves complex multifactorial mechanisms including bone remodeling inhibition, inflammation, and angiogenesis inhibition. Recent research has identified the involvement of osteoblasts and the Wnt signaling pathway in BRONJ development.

Objective

To investigate the effects of Agaricus blazei polysaccharide (PAb) gel on bone tissue in rats with bisphosphonate-related osteonecrosis of the jaw (BRONJ). The study hypothesized that PAb gel could stimulate bone formation and alleviate BRONJ by activating Wnt signaling pathways.

Results

PAb gel significantly improved bone tissue outcomes by increasing viable osteocyte numbers (reversing 52% reduction), reducing empty lacunae, and decreasing bone sequestration. The treatment stimulated osteoblast activity through Wnt signaling pathway activation (increased β-catenin and Runx2 expression, decreased GSK3β). PAb gel also enhanced bone quality by increasing total and type I collagen, improving mineral-to-matrix ratios, and reducing bone solubility compared to bisphosphonate-treated controls.

Conclusion

PAb gel derived from Agaricus blazei effectively mitigated bone necrosis in the BRONJ model by stimulating bone remodeling through Wnt signaling pathway activation and concurrent improvement in bone quality. The findings suggest PAb gel emerges as a promising pharmacological tool for aiding BRONJ therapy or potentially preventing BRONJ development, though further clinical trials are needed to validate efficacy and safety in human patients.
  • Published in:Scientific Reports,
  • Study Type:Preclinical Randomized Controlled Study,
  • Source: PMID: 38589479, DOI: 10.1038/s41598-024-58445-5
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