Tat SK et al. – Osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) levels, and consequently the OPG/RANKL ratio, differed according to human OA subchondral bone osteoblast classification; it is decreased in L and increased in H OA. These findings strongly suggest that the metabolic state of the L OA osteoblasts favours bone resorption. Methods
Study to investigate the OPG and RANKL expression levels, the histologic analysis of the subchondral bone as well as the osteoclast differentiation effect of osteoblasts
Gene expression was determined using RT-PCR, PGE2 and OPG levels by specific ELISA, and membranous RANKL by flow cytometry
Histological observation of the subchondral bone was performed on human knee specimens
Osteoclast differentiation and formation was assayed by using the pre-osteoclastic cell line RAW 264.7
OPG and RANKL modulation on L OA osteoblasts was monitored following treatment with osteotropic factors
Resorption activity was studied by the co-culture of differentiated PBMC/osteoblasts
Results
Human OA subchondral bone osteoblasts expressed less OPG than normal
Compared to normal, RANKL gene expression levels were increased in L OA and decreased in H OA cells
The OPG/RANKL mRNA ratio was diminished in L OA vs normal or H OA and markedly increased in H OA vs normal
Inhibition of endogenous PGE2 levels by indomethacin markedly decreased the ratio of OPG/RANKL on the H OA
In contrast to H OA osteoblasts, L OA cells induced a higher level of osteoclast differentiation and formation
A reduced subchondral bone on the L OA and an increased bone mass on the H OA was observed vs normal
OPG/RANKL mRNA expression ratio was reduced by vit D3 and increased by TNF-α, PTH and PGE2, while IL-1β demonstrated no effect
OPG protein levels showed similar profiles
No true effect was noted on membranous RANKL upon treatment with IL-1β, PGE2 and PTH, but an increase was observed with vit D3 and TNF-α
The resorption activity of the L OA cells was inhibited by all treatments except IL-1β, with maximum effect observed with vit D3 and PGE2
See all
