Periodontitis induces skeletal muscle atrophy by increasing circulating levels of activin A.

2026-05-06

Periodontitis is linked to various systemic conditions, but its impact on skeletal muscle remains unclear. Here, we utilized a ligature-induced periodontitis model in male mice and showed that periodontitis significantly reduces muscle and bone mass without affecting fat mass or food intake. Interestingly, activin A, well-documented inducer of muscle atrophy, is highly expressed in periodontitis-affected gingiva. The activin A gene ( Inhba ) is predominantly expressed in gingival fibroblasts and epithelial cells, which undergo significant proliferation as periodontitis progresses, as well as in myeloid cells infiltrating inflamed periodontal tissues and myeloid cell-derived osteoclasts. A similar upregulation pattern of INHBA was also confirmed in periodontitis-affected human tissues by scRNA-seq analysis. Furthermore, we demonstrated that serum activin A levels are increased in periodontitis-affected mice and patients. Gingival overexpression of activin A via AAV- Inhba transduction activates canonical activin signaling in skeletal muscle, as evidenced by increased pSMAD3 and MuRF1 expression, leading to significant muscle loss. Notably, intra-gingival injection of si Inhba significantly reduced serum activin A levels and restored muscle mass and myofiber size. Our findings indicate that activin A is a mediator of muscle atrophy in periodontitis and suggest that local injection of si Inhba may prevent periodontitis-induced muscle atrophy without apparent systemic adverse effects.

Full text

DOI https://doi.org/10.1038/s41467-026-72766-1