To investigate the effects of local injection of different doses of lanthanum chloride （LaCl3） on aseptic inflammation in mice stimulated by wear particles from artificial joints, the particles were prepared by vacuum ball mill in vitro and air-pouch models were performed with 45 male BALB/c mice that were randomly divided into blank control group, wear particle group and wear parti- cle ＋ LaCl3 （0.1, 0.9 and 8.1 μmol） group. All animals were sacrificed and tissue specimens were harvested 7 days after treatment. Hematoxylin and eosin （H＆E） staining, enzyme-linked immunosorbent assay （ELISA）, reverse transcription-polymerase chain reac- tion （RT-PCR） and western blot were applied to observe inflammatory reaction and detect the expression of pro-inflammatory cyto- kines （TNF-et, IL-1β） and nuclear factor-κB （NF-κB） in mRNA and protein levels in air-pouch membrances. The results showed that wear particles could stimulate aseptic inflammation in vivo effectively; 0.9 μmol LaCl3 could significantly inhibit wear parti- cle-induced gene and protein expression of pro-inflammatory cytokines and NF-Id3 （P〈0.05）; 0.1 and 8. 1 μmol LaCl3 did not exert an inflammation-inhibiting effect and even caused adverse effects at 8.1 μmol. In conclusion, LaC13 played a protective role against wear particle-induced aseptic inflammation dose-dependently, which was involved in NF-κB related signaling pathways.
To explore the impact of different concentrations of lanthanum chloride （LaC13） on critical components of wear particle-mediated signaling pathways in inflammation and osteoclastogenesis, RAW264.7 cells were naturally divided into eight groups and analyzed by CCK-8 assay, flow cytometry, ELISA, RT-PCR and western blot after treatments. The results showed that three concentrations of LaCI3 had no influence on viability of RAW264.7 cells and down-regulated receptor activator of nuclear factor rd3 （RANK） instead of macrophage colony-stimulating factor receptor （M-CSFR）. Additionally, 2.5 and 10 pmol/L LaC13 could signifi- cantly inhibit gene and protein levels of pro-inflammatory cytokines （tumor necrosis factor-or and interleukin-113, i.e., TNF-ct and IL-113） and NF-r,B/p65, but 100 pmol/L LaC13 did not exert an obvious inflammation-inhibiting effect, and even induced inflamma- tion. In conclusion, these findings demonstrated that LaC13 was able to suppress wear particle-induced inflammation and activation of NF-rd3 in a certain range of concentrations in vitro and mainly decrease the expression of RANK, but not M-CSFR, all of which were generally recognized to play a pivotal role in osteoclastogenesis.
