The Expression Profile And Potential Mechanisms Of Lipoxygenase Family In Periodontitis And Diabetes-associated Periodontitis

ObjectivePeriodontitis is a chronic inflammatory disease which is affected by diabetes.In arachidonic acid metabolism,lipoxygenases pathway is involved in the development of inflammatory diseases and diabetes.This study aims to clarify the expression profile and potential pathogenic mechanisms of lipoxygenases in periodontitis and diabetes-associated periodontitis.MethodsIn the present study,gingival tissues from periodontitis patients were collected to investigate the expression profile of lipoxygenase family.The potential pathogenic mechanisms of lipoxygenases were speculated by Spearman’s correlation analysis.By establishing mouse model of diabetesassociated periodontitis,the expression profile of lipoxygenases in gingival tissues from diabetes-associated periodontitis was examined.Finally,the effect of the product of ALOX12,12(S)-HETE,on the osteogenic differentiation of BMSC was investigated.ResultsCompared with healthy gingival tissues,ALOX5(p<0.05)and ALOX15B(p<0.001)was upregulated in periodontitis.Functionally,ALOX5 was positively correlated with TNF-α、MMP-8、MMP-9 and RANKL,and ALOX15 B was positively correlated with MMP-8 and RANKL.Compared with experimental periodontitis,ALOX12 was upregulated in the gingival tissues from diabetes-associated periodontitis in mice(p<0.01).High glucose could induce ALOX12 expression in BMSC.Besides,the osteogenic differentiation of BMSC was inhibited by the 12(S)-HETE,the product of ALOX12,companied with the activated p38 MAPK and suppressed BMP2/Smad signaling pathway.ConclusionIn human periodontitis gingival tissues,ALOX5 and ALOX15 B were upregulated and may involve in the regulation of inflammation,connective tissue destruction and osteoclastogenesis.Compared with experimental periodontitis,ALOX12 was upregulated in gingival tissues from diabetesassociated periodontitis in mice.In addition,the product of ALOX12,12(S)-HETE,may inhibit the osteogenic differentiation of BMSC by activating p38 MAPK pathway and inhibiting BMP2/Smad pathway,resulting in the disorder of bone metabolism in periodontitis.