Silencing mitogen-activated protein kinase-activated protein kinase-2 arrests inflammatory bone loss

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorLi, Qiyan
dc.creatorYu, Hong
dc.creatorZinna, Robert
dc.creatorMartin, Kylie
dc.creatorHerbert, Betthany
dc.creatorLiu, Angen
dc.creatorRossa Júnior, Carlos
dc.creatorKirkwood, Keith L.
dc.date2015-08-06T16:12:50Z
dc.date2016-10-25T20:53:28Z
dc.date2015-08-06T16:12:50Z
dc.date2016-10-25T20:53:28Z
dc.date2011
dc.date.accessioned2017-04-06T08:35:35Z
dc.date.available2017-04-06T08:35:35Z
dc.identifierThe Journal of Pharmacology and Experimental Therapeutics, v. 336, p. 633-642, 2011.
dc.identifier0022-3565
dc.identifierhttp://hdl.handle.net/11449/125692
dc.identifierhttp://acervodigital.unesp.br/handle/11449/125692
dc.identifierhttp://dx.doi.org/10.1124/jpet.110.172395
dc.identifier7634063102292261
dc.identifierhttp://jpet.aspetjournals.org/content/336/3/633.full
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/936286
dc.descriptionp38 mitogen-activated protein kinases (MAPKs) are critical for innate immune signaling and subsequent cytokine expression in periodontal inflammation and bone destruction. In fact, previous studies show that systemic p38 MAPK inhibitors block periodontal disease progression. However, development of p38 MAPK inhibitors with favorable toxicological profiles is difficult. Here, we report our findings regarding the contribution of the downstream p38 MAPK substrate, mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAPK-2), in immune response modulation in an experimental model of pathogen-derived lipopolysaccharide (LPS)-induced periodontal bone loss. To determine whether small interfering RNA (siRNA) technology has intraoral applications, we initially validated MK2 siRNA specificity. Then, gingival tissue surrounding maxillary molars of rats was injected with MK2 siRNA or scrambled siRNA at the palatal regions of bone loss. Intraoral tissues treated with MK2 siRNA had significantly less MK2 mRNA expression compared with scrambled siRNA-treated tissues. MK2 siRNA delivery arrested LPS-induced inflammatory bone loss, decreased inflammatory infiltrate, and decreased osteoclastogenesis. This proof-of-concept study suggests a novel target using an intraoral RNA interference strategy to control periodontal inflammation.
dc.languageeng
dc.relationThe Journal of Pharmacology and Experimental Therapeutics
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectInnate immunity
dc.subjectCell signaling
dc.subjectBone resorption
dc.subjectRANKL
dc.subjectImmunology
dc.titleSilencing mitogen-activated protein kinase-activated protein kinase-2 arrests inflammatory bone loss
dc.typeOtro


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