Pathogenesis of gout: Exploring more therapeutic target.

Gout is a chronic metabolic and immune disease, and its specific pathogenesis is still unclear. When the serum uric acid exceeds its saturation in the blood or tissue fluid, it is converted to monosodium urate crystals, which lead to acute arthritis of varying degrees, urinary stones, or irreversible peripheral joint damage, and in severe cases, impairment of vital organ function. Gout flare is a clinically significant state of acute inflammation in gout. The current treatment is mostly anti-inflammatory analgesics, which have numerous side effects with limited treatment methods. Gout pathogenesis involves many aspects. Therefore, exploring gout pathogenesis from multiple perspectives is conducive to identifying more therapeutic targets and providing safer and more effective alternative treatment options for patients with gout flare. Thus, this article is of great significance for further exploring the pathogenesis of gout. The author summarizes the pathogenesis of gout from four aspects: signaling pathways, inflammatory factors, intestinal flora, and programmed cell death, focusing on exploring more new therapeutic targets.

OPG inhibits gene expression of RANK and CAII in mouse osteoclast-like cell.

This study was designed to determine the effects of the osteoprotegerin (OPG) on the mRNA expression of carbonic anhydrase II (CAII) and the receptor activator of NF-κB (RANK) in mouse osteoclast-like cells. Marrow cells were harvested from femora and tibiae of mouse and cultured in 6-well chamber slides. After 1 day of incubation, the marrow cells were exposed to M-CSF (25 ng/ml), RANKL (50 ng/ml), and different concentrations of OPG (50, 75, and 100 ng/ml, respectively) for 3 days. Osteoclast-like cells were confirmed by both tartrate-resistant acid phosphatase (TRAP) stain and bone resorption assay. The expression of RANK and CAIImRNA was determined with real-time fluorescent quantitative polymerase chain reaction. The numbers of multinucleated, TRAP-positive osteoclast-like cells, and resorption pits formed were observed. Compared with the M-CSF + RANKL group, RANKmRNA expression was statistically decreased in the M-CSF and M-CSF + RANKL + OPG (100 ng/ml) groups (P = 0.004, P = 0.024, respectively); Compared with the M-CSF, M-CSF + RANKL, and M-CSF + RANKL + OPG (100 ng/ml) group, CAIImRNA expression in the M-CSF + RANKL + OPG (75 ng/ml) groups was statistically decreased (P = 0.001, P = 0.008, and P = 0.036, respectively). These data suggest that OPG could regulate the expression of RANK and CA II mRNA in the marrow culture system.