IL‐1β differently stimulates proliferation and multinucleation of distinct mouse bone marrow osteoclast precursor subsets

[摘要] Osteoclastsarebone‐resorbingcellsandtargetsfortreatingbonediseases.Previously,wereportedthatdistinctmurineosteoclastprecursorsubsets,suchasearlyblasts(CD31hiLy‐6C−),myeloidblasts(CD31+Ly‐6C+),andmonocytes(CD31−Ly‐6Chi),responddifferentlytotheosteoclastogenesis‐inducingcytokines,macrophagecolony‐stimulatingfactor,andreceptoractivatorfornuclearfactorκBligand.Itisunknown,however,howthesecelltypesrespondtotheosteoclast‐stimulatinginflammatorycytokineinterleukin1β.Thisstudyaimstoinvestigatetheeffectofinterleukin1βonosteoclastogenesisderivedfromdifferentmousebonemarrowprecursors.Earlyblasts,myeloidblasts,andmonocytesweresortedfrommousebonemarrowcellsusingflowcytometry.Cellswereculturedonplasticoronboneslicesinthepresenceofmacrophagecolony‐stimulatingfactorandreceptoractivatorfornuclearfactorκBligand,withoutorwithinterleukin1β(0.1–10ng/ml).Wefoundthatinterleukin1βstimulatedmultinucleationandboneresorptionofosteoclastsderivedfromthe3precursorsatdifferentrates.Themostlargeosteoclasts(>20nuclei)andhighestlevelofboneresorption(16.3%)wasbymyeloidblast–derivedosteoclasts.Interleukin1βparticularlyacceleratedproliferationofearlyblastsandthemostsmallosteoclasts(3–5nuclei)formedonplastic.Lifespanvariedamongosteoclastsderivedfromdifferentprecursors:largeosteoclasts(>2400µm2)formedmostrapidly(75h)frommyeloidblastsbuthadashortlifespan(30h).Monocytesneededthelongesttime(95h)forthegenerationofsuchlargeosteoclasts,butthesecellshadalongerlifespan(50h).Ourresultsindicatethatthedifferentbonemarrowosteoclastprecursorsaredifferentlystimulatedbyinterleukin1βwithrespecttoproliferation,multinucleation,lifespan,andboneresorption...

[学科分类] 生理学

[关键词] early blasts;myeloid blasts;monocytes;osteoclastogenesis;bone resorption