RRC ID 71741
Author Balint E, Marshall CF, Sprague SM.
Title Role of interleukin-6 in beta2-microglobulin-induced bone mineral dissolution.
Journal Kidney Int
Abstract BACKGROUND:beta2-microglobulin (beta2m) amyloidosis is commonly seen in patients undergoing long-term dialysis. beta2m has been shown to induce in vitro bone mineral dissolution. The present study was designed to investigate the effect of beta2m on osteoblast function and the role of interleukin-6 (IL-6) on beta2m-induced bone resorption.
METHODS:Using neonatal mouse calvariae as well as primary osteoblasts and MC 3T3 osteoblast-like cells, IL-6 production, release, and gene expression were investigated with enzyme-linked immunosorbent assay (ELISA) and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) techniques, respectively.
RESULTS:In calvariae, beta2m induced a time- and dose-dependent calcium release, which was maximum following a 48-hour incubation at a concentration of 10-5 mol/L. beta2m (10-6 mol/L) also induced a significant release of IL-6 from calvarial and primary osteoblastic cultures. Using 10-6 mol/L beta2m, the amount of IL-6 mRNA in MC 3T3 cells increased in a time-dependent fashion, which peaked at 3 hours and declined to baseline by 12 hours. In primary osteoblast cells, beta2m maximally increased IL-6 mRNA levels at 6 hours; however, they remained elevated up to 24 hours. Compared with control, the presence of beta2m significantly increased cell proliferation of both primary osteoblasts and MC 3T3 cells. To investigate osteoblastic function further, osteocalcin mRNA was quantitated. Incubation with beta2m for 3 to 24 hours did not alter the amount of osteocalcin mRNA in the MC 3T3 osteoblast cells.
CONCLUSION:beta2m affects bone metabolism by mechanisms that include increasing IL-6 gene expression and release, and enhancing osteoblast proliferation without affecting osteocalcin gene expression.
Volume 57(4)
Pages 1599-607
Published 2000-4-1
DOI 10.1046/j.1523-1755.2000.00004.x
PII S0085-2538(15)46909-1
PMID 10760095
MeSH Animals Bone Density / drug effects* Bone and Bones / cytology Bone and Bones / metabolism Calcium / metabolism Cell Division / drug effects Cells, Cultured Gene Expression / drug effects Interleukin-6 / biosynthesis Interleukin-6 / metabolism Interleukin-6 / physiology* Male Mice Osteoblasts / cytology Osteoblasts / drug effects Osteoblasts / metabolism Osteoblasts / physiology Osteocalcin / genetics RNA, Messenger / metabolism beta 2-Microglobulin / pharmacology*
IF 8.945
Resource
Human and Animal Cells MC3T3-E1(RCB1126)