FTY720Inhibits Bone Destruction Induced By Polyethylene Wear Particles In Mouse Air Pouch Model

Objective: To investigate the effect of FTY720(Fingolimod) onosteolysis induced by ultra-high-molecular-weight polyethylene(UHMWPE) particles in mouse air pouch model.Methods：The air pouches model was established, mice were dividedinto four groups: ultra-high-molecular-weight polyethylene(UHMWPE)particles and FTY720group(UHMWPE was introduced into the airpouches and mice were injected intraperitoneally with FTY720);UHMWPE group(UHMWPE was introduced into the air pouches andmice were injected intraperitoneally with DMSO); FTY720group(normalsaline was introduced into the air pouches and mice were injectedintraperitoneally with FTY720); blank group(normal saline wasintroduced into the air pouches and mice were injected intraperitoneallywith DMSO).Four weeks later, all the mice are sacrificed, pouch walls andimplanted calvaria were collected. The inflammatory reaction and thenumber of exuded inflammatory cells of the pouch walls were detectedthrough HE staining, some of inflammatory cytokines, IL-6and TNF-α, in tissue homogenate were detected with ELISA; the resorption of the boneslices were detected with scanning electron microscopy; the osteoclastassociated gene TRAP in pouch tissues were detected with RT-PCR.Results:①HE staining results showed that the number of exudedinflammatory cells of the pouch walls in the UHMWPE and FTY720group(4892±457)had no difference compared with the UHMWPEgroup(4931±572)(P>0.05),there was no difference between the FTY720group(2013±375)and the blank group(2151±310)(P>0.05); butinflammatory cell amounts in the UHMWPE groups were higher thanthe groups that without treatment UHMWPE(P<0.05).②ELISA resultsshowed that the quantity of inflammatory cytokines IL-6and TNF-α intissue homogenate in the UHMWPE and FTY720group[(130.13±3.22),(129.22±5.02)]had no difference compared with theUHMWPE group[(149.22±6.09),(140.52±2.68)](P>0.05), there was nodifference between the FTY720group[(68.24±2.83),(82.88±5.34)] and theblank group[(69.51±2.31),(74.15±4.64)](P>0.05); but the inflammatorycytokine(IL-6and TNF-α) concentrations in the UHMWPE groups werehigher than the groups that without treatment UHMWPE(P<0.05).③Scanning electron microscopy showed that the area of resorption of thebone slices in the UHMWPE and FTY720group[(10.21±1.78)%] waslower than the UHMWPE group[(17.79±2.56)%], the FTY720group[(1.82±1.37)%] was lower than the blank groups[(6.27±2.11)%]; and the area of resorption of the bone slices in the UHMWPE groups werehigher than the groups that without treatment UHMWPE(P<0.05).④RT-PCR results showed that osteoclasts-associated TRAP mRNA in theUHMWPE and FTY720group(0.53±0.04)was lower than the UHMWPEgroup(0.74±0.05), the FTY720group(0.22±0.03) was lower than the blankgroup(0.38±0.04); and osteoclasts-associated TRAP mRNA in theUHMWPE groups were higher than the groups that without treatmentUHMWPE(P<0.05).Conclusion：FTY720could inhibit the bone destruction that causedby the UHMWPE in mouse air pouch mode.