Branched-chain amino acids promote gelatinase secretion from human periodontal ligament stem cells through nuclear factor kappa-B signaling

Abstract

Objective

To explore the effects of branched-chain amino acids (BCAAs) on periodontal tissues and regulation of gelatinase secretion by human periodontal ligament stem cells (hPDLSCs).

Design

The salivary BCAA levels (leucine, isoleucine, and valine) in the clinical participants were measured using mass spectrometry. A local injection model in the periodontium of Sprague Dawley rats was established to investigate the periodontal destruction induced by BCAAs. A BCAA-treatment model of hPDLSCs was established to detect the expression and activity of gelatinase and further explore the potential mechanism by which BCAAs enhance gelatinase secretion.

Results

Compared to the healthy controls, the salivary levels of leucine (p = 0.0190), isoleucine (p = 0.0351), and valine (p = 0.0072) were significantly elevated in individuals with periodontitis. In vivo experiments revealed that BCAAs aggravated periodontal extracellular matrix degradation and alveolar bone resorption in rats. Three-dimensional reconstruction of the rat maxilla demonstrated an increase in the distance from the cementoenamel junction to the alveolar bone crest (p < 0.0001), and a decrease in the bone volume fraction (p < 0.0001). In vitro experiments demonstrated that BCAAs activate the phosphorylation of nuclear factor kappa-B (NF-κB) signaling pathway in the hPDLSCs and consequently induce the secretion of gelatinases. The absence of any of the components in the BCAAs attenuated this effect.

Conclusion

BCAAs increase gelatinase secretion through the NF-κB (p-p65) signaling pathway, consequently exacerbating periodontal tissue destruction. This provides a novel insight on the role of BCAAs in the host immune-inflammatory response and increases our understanding of the possible involvement of BCAAs in the periodontitis development.