Anti-inflammatory effect of polydeoxyribonucleotide on zoledronic acid-pretreated and lipopolysaccharide-stimulated RAW 264.7 cells.

Bisphosphonates are generally used as therapeutic agents for bone diseases. However, previous reports on bisphosphonates-related osteonecrosis of the jaw (BRONJ) demonstrated that inflammation triggers and worsens the disease. Recently, polydeoxynucleotide (PDRN), an A2A receptor agonist, has been suggested for the treatment of various diseases and broadly studied for its anti-inflammatory effect. The present study aimed to measure the effect of PDRN on macrophage cells treated with zoledronic acid (ZA) and lipopolysaccharide (LPS). Macrophage cells were cultured with ZA for 24 h, following which they were stimulated with LPS in the presence or absence of varying concentrations of PDRN for 24 h. The cell viability and nitric oxide (NO) production of the cells were analyzed. In addition, protein expression levels were quantified by western blotting. Cell viability was compromised and NO was overexpressed by ZA and LPS stimulation. However, under ZA and LPS stimulation cell viability was enhanced, and NO production, and inducible nitric oxide synthase, interleukin (IL)-1β, -6, and tumor necrosis factor-α overexpression were suppressed on exposure to PDRN. A2A receptor and vascular endothelial growth factor (VEGF) expression levels increased following PDRN treatment. These results indicate that PDRN treatment of macrophages inhibits the inflammatory cytokines induced by ZA and LPS stimulation. It was hypothesized that the inflammatory cytokines were inhibited through A2A activation by PDRN. In addition, increased VEGF expression may contribute to increased vascularization and subsequently improve the pathological condition in BRONJ. As inflammation and LPS may stimulate the occurrence of BRONJ, the present study postulated that PDRN is possibly a candidate for the therapeutic management of BRONJ by decreasing inflammation and increasing vascularization.