Effects Of Lanthanum Chloride On Wear Particle-induced Aseptic Inflammation In Vitro And In Vivo Experimental Researches

Objective：To provide the theoretical basis for effects and mechanisms of lanthanumchloride on wear particle-induced inflammatory osteolysis, it was investigated whatwere in vivo and in vitro effects of different concentrations and doses of lanthanumchloride (LaCl3) on the aseptic inflammation stimulated by artificial joint wearparticles.Methods：Artificial joint wear particles were prepared by vacuum ball mill in vitro.In vitro, RAW264.7cells were naturally divided into eight groups: blank controlgroup, wear particle group, wear particle+LaCl3(2.5μmol/L,10μmol/L and100μmol/L) group and LaCl3(2.5μmol/L,10μmol/L and100μmol/L) group. After48htreatments, each group was analyzed by CCK-8assay and flow cytometry torespectively detect cell viability and apoptosis; ELISA, RT-PCR and western blotwere employed to detect gene and protein expression levels of TNF-α, IL-1β andNF-κB. In vivo, murine air-pouch models were performed with45male BALB/cmice that were randomly divided into blank control group, wear particle group andwear particle+LaCl3(0.1μmol,0.9μmol and8.1μmol) group. All animals weresacrificed and tissue specimens were harvested at7days after grouping. HE stainingwas applied to observe inflammatory reaction; ELISA, RT-PCR and western blotwere employed to detect mRNA and protein levels of TNF-α, IL-1β and NF-κB in themurine air-pouch membrances.Results：During treatments, three concentrations and doses of LaCl3had no influenceon the viability of RAW264.7cells and the survival of mice. Wear particles preparedby vacuum ball mill in vitro could stimulate aseptic inflammation in vivo and in vitroeffectively. In vitro,2.5μmol/L and10μmol/L LaCl3could significantly inhibit thegene and protein expressions of TNF-α, IL-1β and NF-κB (P<0.05), but100μmol/LLaCl3did not exert an obvious inflammation-inhibiting effect, and even in turnpromoted inflammation. In vivo,0.9μmol LaCl3could inhibit the gene and proteinexpressions of TNF-α, IL-1β and NF-κB (P<0.05);0.1μmol and8.1μmol LaCl3didnot exert an inflammation-inhibiting effect and even caused adverse effects at 8.1μmol.Conclusion：LaCl3in present study shows no toxicity to the RAW264.7cells and theBALB/c mice; the wear particle-induced aseptic inflammation in vivo and in vitro canbe inhibited by LaCl3in a certain range of concentrations and doses, the mechanismof which is involved in the inhibition of NF-κB activation; the inhibitory effects ofLaCl3are concentration-and dose-dependent, LaCl3outside the range not only can’tinhibit the aseptic inflammation, but even has a tendency to cause opposite and otheradverse effects.