Osteoprotegerin is elevated in pulmonary fibrosis and associates with IPF progression: a pilot study

Introduction: Osteoprotegerin (OPG), a decoy receptor for receptor activator of NF-κB ligand (RANKL), serves as a biomarker for liver fibrosis severity. Our recent findings show OPG production in fibrotic lung tissue, though its specific cellular source and role in pulmonary fibrosis are unknown. We hypothesized that OPG is produced by fibroblasts and serves as a marker for pulmonary fibrosis progression.

Methods: We examined OPG expression in human and mouse control and fibrotic lung tissue and used primary human lung fibroblasts and murine precision-cut lung slices to study OPG production. Serum from idiopathic pulmonary fibrosis (IPF) patients and controls was analyzed to investigate correlations between OPG levels and disease status, as measured by lung function.

Results: OPG-protein levels were significantly higher in murine and human fibrotic lung tissue compared to control. OPG-protein levels in fibrotic mouse lung tissue correlated positively with collagen deposition. OPG-mRNA and protein production increased in mouse lung slices upon TGFβ stimulation. Isolated lung fibroblasts from IPF patients produced more OPG-protein than controls. Serum OPG levels in IPF patients negatively correlated with diffusing capacity to carbon monoxide. Serum OPG levels above 1,243 pg/mL were linked to disease progression in IPF patients.

Conclusion: OPG is produced by fibroblasts in lung tissue, associates with fibrosis, and may be a potential prognostic biomarker for IPF progression. Validation in a larger cohort is necessary to further explore OPG’s role in pulmonary fibrosis and its potential for assessing fibrotic lung disease prognosis in individual patients.