Izazinzulu zichaza ngendima yeproteyini ethile kwisizukulwana seeseli ezibaluleke kakhulu kugcino lwamathambo
Isifo esinganyangekiyo samathambo kunye nezifo ezidibeneyo, ezinjenge-osteoporosis kunye ne-rheumatoid arthritis, zichaphazela izigidi zabantu kwihlabathi liphela, ngakumbi abantu abadala, behlisa umgangatho wobomi babo. Into ebalulekileyo kuzo zombini ezi zifo kukusebenza okugqithisileyo kweeseli ezinyibilikisa amathambo ezibizwa ngokuba zii-osteoclasts. I-Osteoclast yenziwa ngokwahlulahlula kuhlobo oluthile lweeseli zomzimba ezibizwa ngokuba yi-macrophage, emva koko bafumana indima yabo entsha kulondolozo lwamathambo kunye namalungu: ukophula izicubu zethambo ukuvumela ii-osteoblast-olunye uhlobo lweseli-ukulungisa nokulungisa inkqubo yamathambo .
Ngokubanzi, iinkqubo ezimbini ze-intracellular ziyabandakanyeka kolu mahluko: okokuqala, ukukhutshelwa-apho kwenziwa khona i-RNA yomthunywa (i-mRNA) ukusuka kulwazi lwemfuzo kwi-DNA -kwaye emva koko, uguqulo-apho ulwazi kwi-mRNA luchongiwe khona ukuvelisa iiproteni yenza imisebenzi ethile kwiseli. Ukusukela ekufumanekeni kwendima yeprotein ethile ebizwa ngokuba yi-RANKL kulwakhiwo lwe-osteoclast, izazinzulu zisombulule isahlulo esibonakalayo sephazili apho iiseli zibonisa umendo kunye nothungelwano lokukhutshelwa lulawula isizukulwana se-osteoclast. Nangona kunjalo, iinkqubo zeselfowuni ezikhutshelweyo zibandakanyeka zihlala ziqondwa.
Ngoku, kuphononongo olutsha olupapashwe kwi-Biochemical and Biophysical Research Communications, izazinzulu kwiYunivesithi yaseTokyo yezeNzululwazi, eJapan, zaveza indima yeprotein ebizwa ngokuba yiCpeb4 kule nkqubo inzima. I-Cpeb4 yinxalenye ye- "cytoplasmic polyadenylation element binding (CPEB)" yosapho lweeproteni, ezibophelela kwi-RNA kwaye zilawule ukuguqulelwa kokusebenza kunye nengcinezelo, kunye nezinye iindlela "zokuphamba" ezivelisa ukwahluka kweprotein. UGqr Tadayoshi Hayata, owayekhokele kolu phando, uyacacisa: “Iiproteni ze-CPEB ziyanyanzeliswa kwiinkqubo ezahlukeneyo zebhayoloji kunye nezifo, ezinje nge-autism, umhlaza, kunye nokwahluka kweeseli ezibomvu zegazi. Nangona kunjalo, imisebenzi yabo yomahluko we-osteoclast ayaziwa ngokucacileyo. Ke ngoko, siqhube uthotho lwamalinge okubonisa iproteni evela kolu sapho, i-Cpeb4, sisebenzisa iinkcubeko zeseli zeemacrophages zegundane. ”
Kwimvavanyo eyahlukeneyo yenkcubeko yeseli eyenziweyo, ii-macrophage zegundane zavuselelwa nge-RANKL ukwenza umahluko we-osteoclast kunye nokuvela kwenkcubeko kwajongwa. Okokuqala, izazinzulu zafumanisa ukuba i-Cpeb4 gene expression, kwaye ngenxa yoko isixa seproteyini yeCpeb4, inyuke ngexesha lokwahlulahlula i-osteoclast. Emva koko, ngokusebenzisa i-immunofluorescence microscopy, bajonga utshintsho kwindawo ye-Cpeb4 ngaphakathi kweeseli. Bafumanise ukuba i-Cpeb4 isuka kwi-cytoplasm iye kwi-nuclei, ngelixa iveza imilo ethile (ii-osteoclast zihlala zidibana kunye zenze iiseli ezine-nuclei ezininzi). Oku kubonisa ukuba umsebenzi weCpeb4 onxulunyaniswa nokwahlulahlula i-osteoclast kunokwenzeka ukuba wenziwe ngaphakathi kwe-nuclei.
Ukuqonda indlela i-RANKL evuselelayo ebangela ukuba le ndawo i-Cpeb4 isuswe kwakhona, izazinzulu zikhetha "ukuthintela" okanye ukucinezela ezinye zeeprotein ezibandakanyekayo "ezantsi" kwiindlela zangaphakathi zomqondiso ezibangelwa kukukhuthaza. Bachonge iindlela ezimbini eziyimfuneko kwinkqubo. Nangona kunjalo, olunye uvavanyo luya kufuneka ukuba ufunde ngokupheleleyo ngokulandelelana kweziganeko ezenzekayo kunye nazo zonke iiproteni ezichaphazelekayo.
Okokugqibela, uGqr Hayata kunye neqela lakhe babonisa ukuba i-Cpeb4 iyimfuneko yokwenziwa kwe-osteoclast kusetyenziswa iinkcubeko ze-macrophage apho i-Cpeb4 yayiphelile. Iiseli kwezi nkcubeko azikhange ziphinde zenze umahluko wokuba zii-osteoclasts.
Zidibene kunye, iziphumo lilitye lokunyathela ukuqonda iindlela zeselfowuni ezichaphazelekayo ekwakhiweni kwe-osteoclast. Ugqirha Hayata uthi: "Isifundo sethu sikhanyisa indima ebalulekileyo ye-RNA-ebophayo ye-protein Cpeb4" njengempembelelo "yokwahlulahlula i-osteoclast. Oku kusenza siziqonde ngcono iimeko zophendlo lwezifo zamathambo kunye nezifo ezidibeneyo kwaye kunokuba negalelo kuphuhliso lwezicwangciso zonyango lwezifo eziphambili ezinjenge-osteoporosis kunye ne-rheumatoid arthritis. ” Ndiyathemba, inqanaba elinzulu lokuqonda kwesifo se-osteoclast esiququzelelwa lolu phononongo ekugqibeleni liza kuguqulela kumgangatho wobomi ophuculweyo wabantu abaphila nezifo ezibuhlungu zamathambo kunye nokudibana.
Malunga neYunivesithi yaseTokyo yeSayensi
IYunivesithi yaseTokyo yeSayensi (i-TUS) yiyunivesithi eyaziwayo nehlonitshwayo, kunye neyona yunivesithi inkulu kwezophando yabucala eJapan, eneekhampasi ezine kumbindi weTokyo nakwiidolophu zayo naseHokkaido. Eyasungulwa ngo-1881, iyunivesiti iye yaqhubeka igalelo ekuphuhlisweni kweJapan kwisayensi ngokubethelela uthando lwezesayensi kubaphandi, ochwepheshe kunye nootitshala.
Ngomsebenzi "Wokudala isayensi kunye netekhnoloji yophuhliso oluhambelanayo lwendalo, abantu, kunye noluntu", i-TUS yenze uluhlu olubanzi lophando ukusuka kwisiseko ukuya kwisayensi esetyenzisiweyo. Tus uye wamkela indlela ezixubeneyo kuphando kunye nokwenza uphando olunzulu kwezinye iinkalo namhlanje kubaluleke kakhulu. I-TUS yidemokhrasi apho eyona nto ibalaseleyo kwisayensi yamkelwe kwaye yondliwa. Yiyo kuphela eyunivesithi yabucala eJapan evelise iBhaso likaNobel kunye neyunivesithi yabucala kuphela eAsia ukuvelisa abaphumeleleyo beBhaso likaNobel kwicandelo lezenzululwazi yendalo.
Malunga noNjingalwazi oDibeneyo uTadayoshi Hayata ovela kwiYunivesithi yaseTokyo yeSayensi
Ukusukela nge-2018, uGqr Tadayoshi Hayata ubenguNjingalwazi onxulumene naye kunye noMphandi oyiNtloko kwiSebe le-Molecular Pharmacology, iFakhalthi yezeNzululwazi ngamachiza, kwiYunivesithi yaseTokyo yezeNzululwazi. Ilabhoratri yakhe ijolise kwimetabolism yethambo, ukwahluka kweselula, ikhemesti yemolekyuli, kunye neenkalo ezifanayo ukuqonda imeko yesifo samathambo kunye nokudibana kunye nokufumana iithagethi zonyango. UGqr Hayata unxulumana neMibutho eliqela yaseJapan kunye noMbutho waseMelika woPhando lweMathambo kunye nezeZimbiwa. Upapashe ngaphezulu kwama-50 amanqaku okuqala kwaye wanika ngaphezulu kwe-150 yeenkcazo kwiinkomfa zezifundo. Ukongeza, uphando lwakhe kwi-osteoporosis luyenzile kumaphephandaba aseJapan amatyeli aliqela.
Ulwazi ngezemali
Olu phononongo luxhaswe nguJSPS KAKENHI [inombolo yesibonelelo 18K09053]; INanken-Kyoten, i-TMDU (2019); iSiseko seNakatomi; Inkxaso yoPhando nge-Astellas; Igalelo leMfundo likaPfizer; I-Daiichi-Sankyo Igalelo leMfundo; Igalelo lezefundo laseTeijin Pharma; Igalelo lezemfundo laseJapan uEli Lilly; Igalelo leOtsuka Pharmaceutical Academic; Igalelo lezeMfundo eShionogi; Igalelo leChugai Pharmaceutical Academic.
