The RANKL-OPG balance in pulmonary fibrosis

Alveolar macrophages express Receptor Activator of NF-κB (RANK), which is a known regulator of bone matrix turnover. Upon binding of its ligand RANKL, extracellular matrix (ECM) degradation can be induced. This interaction is inhibited by osteoprotegerin (OPG), the decoy receptor of RANKL and previously found to be elevated in pulmonary fibrosis (PF). We hypothesized that OPG in PF dampens ECM degradation by macrophages leading to fibrosis and proceeded to characterize and influence the system in lung tissue. We compared RANKL and OPG protein levels in lung tissue of PF patients (n=11) and controls (n=16), and control and PF mice (n=6). Exact sources were determined by immunohistochemistry, ELISA, and flow cytometry. Furthermore, mice with established PF were treated with soluble RANKL followed by total lung collagen analysis to assess PF. PF patients and mice had significantly higher OPG levels in lung tissue compared to their respective controls (p ECM modulator OPG is differentially expressed in healthy versus fibrotic conditions and induction of OPG following RANKL treatment suggests that the balance with RANKL is tightly regulated. These results support the importance of a RANKL-OPG balance in PF and may constitute a new target for treatment.