Regulation of osteoclast structure and function by FAK family kinases

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: Pyk2;    podosome;    M‐;    CSF;   

DOI  :  10.1189/jlb.0512259

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Osteoclastsarehighlyspecializedcellsthatresorbboneandcontributetoboneremodeling.Diseasessuchasosteoporosisandosteolyticbonemetastasisoccurwhenosteoclast‐mediatedboneresorptiontakesplaceintheabsenceofconcurrentbonesynthesis.Considerableefforthasbeenplacedonidentifyingmoleculesthatregulatetheboneresorptionactivityofosteoclasts.Tothisend,weinvestigateduniqueandoverlappingfunctionsofmembersoftheFAKfamily(FAKandPyk2)inosteoclastfunctions.Withtheuseofaconditionalknockoutmousemodel,inwhichFAKisselectivelytargetedfordeletioninosteoclastprecursors(FAKΔmyeloid),wefoundthatlossofFAKresultedinreducedboneresorptionbyosteoclastsinvitro,coincidentwithimpairedsignalingthroughtheCSF‐1R.However,bonearchitectureappearednormalinFAKΔmyeloidmice,suggestingthatPyk2mightfunctionallycompensateforreducedFAKlevelsinvivo.Thiswassupportedbydatashowingthatpodosomeadhesionstructures,whichareessentialforbonedegradation,weresignificantlymoreimpairedinosteoclastswhenFAKandPyk2werereducedthanwheneithermoleculewasdepletedindividually.WeconcludethatFAKcontributestocytokinesignalingandboneresorptioninosteoclastsandpartiallycompensatesfortheabsenceofPyk2tomaintainproperadhesionstructuresinthesecells...

【 授权许可】

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