The role and its significance of the receptor activator of nuclear factor-κB ligand in arterial calcification

Abstract

Objective To investigate the mechanism that receptor activator of NF-κB ligand(RANKL)promotes arterial calcification. Methods Firstly, RANKL was added into the culture media, in which the monocyte precursor cells alone were cultured.Morphological observation and tartrate resistant acid phosphatase(TRAP)stain were used to assess whether RANKL could induce the monocyte precursor cells to differentiate into osteoclast-like cells.During arterial calcification, both in vivo and in vitro expressions of RANKL and osteoprotegerin(OPG, as RANKL inhibitor)were measured via real-time PCR.The extent of osteoclast-like cell differentiation was also assessed. Results It was found that RANKL could induce osteoclast-like cell differentiation.There were no both in vivo and in vitro expressions of osteoclast-like cells in the early stage of calcification.At that time, the ratio of RANKL to OPG was very low.In the late stage of calcification, a small amount of osteoclast-like cell expression coincided with a relatively high ratio of RANKL to OPG.According to the results, the ratio of RANKL to OPG was very low during most of the arterial calcification period.This made it possible for OPG to completely inhibit RANKL-induced osteoclast-like cell differentiation.The ratio of RANKL to OPG was(0.36±0.08)(F=36)and(1.68±0.08)(F=36)respectively in the early and late subgroup of calcification group in the animal model, but was zero in the control group(both P<0.05). The ratio of RANKL to OPG was(0.42±0.09)(F=16)and(1.50±0.10)(F=16)respectively in the early and late subgroup of calcification group in the cell model, but was zero in the control group(both P<0.05). Conclusions Our result likely explains why RANKL has the ability to induce osteoclast-like cell differentiation, but acts as a promoter of calcification. Key words: NF-kappaB; Osteoclast; Arterial Calcification