Ososayensi bachaza indima yephrotheni ethile ekukhiqizeni amaseli abalulekile ekugcinweni kwamathambo
Izifo ezingelapheki zamathambo namalunga, njenge-osteoporosis nesifo samathambo, zithinta izigidi zabantu emhlabeni wonke, ikakhulukazi asebekhulile, zehlisa izinga lokuphila kwabo. Isici esibalulekile kuzo zombili lezi zifo ukusebenza ngokweqile kwamangqamuzana ahlakaza amathambo abizwa ngokuthi ama-osteoclast. Ama-osteoclast akhiwa ngokuhlukaniswa ohlotsheni oluthile lwengqamuzana lokuzivikela ezifweni olubizwa ngokuthi i-macrophage, ngemva kwalokho athola indima yawo entsha ekugcineni amathambo namalunga: ukubhidliza izicubu zamathambo ukuze kuvunyelwe ama-osteoblasts—olunye uhlobo lwengqamuzana—ukuba alungise futhi alungise kabusha isimiso sohlaka lwamathambo. .
Ngobubanzi, izinqubo ezimbili ze-intracellular zihilelekile kulokhu kuhlukaniswa: okokuqala, ukuloba-lapho isithunywa i-RNA (mRNA) sidalwa kusuka kulwazi lofuzo ku-DNA-bese-ke, ukuhumusha-lapho ulwazi oluku-mRNA lunqunywa khona ukukhiqiza amaprotheni. yenza imisebenzi ethile kuseli. Kusukela kwatholakala indima yephrotheni ethile ebizwa ngokuthi i-RANKL ekwakhekeni kwe-osteoclast, ososayensi baxazulule ingxenye enkulu yendida lapho izindlela zokubonisa amaseli kanye namanethiwekhi okulotshwa alawula ukukhiqizwa kwe-osteoclast. Kodwa-ke, izinqubo zamaselula zangemuva kokulotshwa ezihilelekile zisazoqondwa.
Manje, ocwaningweni olusha olushicilelwe ku-Biochemical and Biophysical Research Communications, ososayensi base-Tokyo University of Science, e-Japan, badalule indima yephrotheni ebizwa nge-Cpeb4 kule nqubo eyinkimbinkimbi. I-Cpeb4 iyingxenye “ye-cytoplasmic polyadenylation element binding (CPEB)” yomndeni wamaprotheni, abophezela ku-RNA futhi alawule ukwenziwa kusebenze kokuhumusha kanye nokucindezelwa, kanye “nezinye izindlela zokuhlanganisa” ezikhiqiza ukuhlukahluka kwamaprotheni. UDkt Tadayoshi Hayata, obehola lolu cwaningo, uyachaza: “Amaprotheni e-CPEB abandakanyeka ezinqubweni ezihlukahlukene zebhayoloji nezifo, njenge-autism, umdlavuza, nokuhlukaniswa kwamangqamuzana abomvu egazi. Kodwa-ke, imisebenzi yabo ekuhlukaniseni i-osteoclast ayaziwa ngokucacile. Ngakho-ke, senze uchungechunge lokuhlola ukuze sibonise iphrotheni evela kulo mndeni, i-Cpeb4, sisebenzisa amasiko amaseli we-macrophages yegundane. "
Ezivivinyweni ezihlukahlukene zesiko lamaseli olwenziwa, ama-macrophage egundane akhuthazwa nge-RANKL ukuze aqalise ukuhlukaniswa kwe-osteoclast futhi ukuvela kwesiko kwaqashwa. Okokuqala, ososayensi bathola ukuthi i-Cpeb4 gene expression, futhi ngenxa yalokho inani le-Cpeb4 protein, lenyuka ngesikhathi sokuhlukaniswa kwe-osteoclast. Khona-ke, nge-microscopy ye-immunofluorescence, babona ngeso lengqondo izinguquko endaweni ye-Cpeb4 ngaphakathi kwamaseli. Bathole ukuthi i-Cpeb4 isuka ku-cytoplasm iye ku-nuclei, kuyilapho yethula izimo ezithile (ama-osteoclast avame ukuhlangana ndawonye futhi akhe amaseli anama-nuclei amaningi). Lokhu kubonisa ukuthi umsebenzi we-Cpeb4 ohlotshaniswa nokuhlukaniswa kwe-osteoclast cishe wenziwa ngaphakathi kwe-nuclei.
Ukuze uqonde ukuthi ukugqugquzelwa kwe-RANKL kubangela kanjani lokhu kususwa kabusha kwe-Cpeb4, ososayensi ngokukhetha "bavimbele" noma bacindezela amanye amaprotheni abandakanyeka "ezansi komfula" ezindleleni zokusayina ze-intracellular ezibangelwa ukukhuthazwa. Bahlonze izindlela ezimbili ezidingekayo kule nqubo. Noma kunjalo, kuzodingeka ukuhlola okwengeziwe ukuze kufundwe ngokugcwele ngokulandelana kwezenzakalo ezenzekayo nawo wonke amaprotheni ahilelekile.
Ekugcineni, uDkt Hayata nethimba lakhe babonise ukuthi i-Cpeb4 iyadingeka ngempela ekwakhekeni kwe-osteoclast kusetshenziswa amasiko e-macrophage lapho i-Cpeb4 yaqedwa khona. Amaseli kulawa masiko awazange aphinde ahluke ukuze abe ama-osteoclast.
Ihlanganiswe ndawonye, imiphumela iyisitebhisi sokuqonda izinqubo zamaselula ezihilelekile ekwakhekeni kwe-osteoclast. UDkt Hayata uyaphawula: “Ucwaningo lwethu lusikhanyisela ngendima ebalulekile yephrotheni ebopha i-RNA i-Cpeb4 “njengethonya” elihle lokuhlukanisa i-osteoclast. Lokhu kusenza siziqonde kangcono izimo zokugula kwezifo zamathambo namalunga futhi kungase kube nomthelela ekwakhiweni kwamasu okwelapha izifo ezinkulu ezifana ne-osteoporosis nesifo samathambo.” Ngethemba, izinga elijulile lokuqonda isizukulwane se-osteoclast esiqhutshwa yilolu cwaningo ekugcineni lizohumusha izinga lempilo elithuthukisiwe kubantu abaphila nezifo ezibuhlungu zamathambo namalunga.
Mayelana neTokyo University of Science
I-Tokyo University of Science (TUS) iyunivesithi eyaziwa futhi ehlonishwayo, futhi iyunivesithi enkulu kunazo zonke yocwaningo oluzimele lwesayensi eJapan, enamakhampasi amane enkabeni yeTokyo namaphethelo ayo naseHokkaido. Isungulwe ku-1881, inyuvesi ibilokhu inikele ekuthuthukeni kweJapan kwezesayensi ngokugxilisa uthando lwesayensi kubaphenyi, ochwepheshe, nakothisha.
Ngomsebenzi "Wokwakha isayensi nobuchwepheshe bokuthuthukiswa okuhambisanayo kwemvelo, abantu, nomphakathi", i-TUS yenze ucwaningo oluningi kusuka kusisekelo kuya kwesayensi esetshenzisiwe. I-TUS yamukele indlela ehlukahlukene yokwenza ucwaningo futhi yenza ucwaningo olunzulu kweminye yemikhakha ebaluleke kakhulu namuhla. I-TUS iyinhlangano yentando yeningi lapho okungcono kakhulu kwisayensi kuqashelwa futhi kunakekelwe khona. Yiyona kuphela eyunivesithi yangasese eJapan ekhiqize owazuza umklomelo weNobel kanye neyunivesithi yangasese kuphela e-Asia yokukhiqiza abawine uMklomelo kaNobel emkhakheni wesayensi yemvelo.
Mayelana NoSolwazi Ohlangene u-Tadayoshi Hayata wase-Tokyo University of Science
Kusukela ngo-2018, uDkt Tadayoshi Hayata ubenguSolwazi Odidiyelwe kanye Nomphenyi Oyinhloko eMnyangweni We-Molecular Pharmacology, Faculty of Pharmaceutical Science, e-Tokyo University of Science. Ilabhorethri yakhe igxile kumetabolism yamathambo, ukuhlukaniswa kwamangqamuzana, i-pharmacology yamangqamuzana, kanye nezinkambu ezifanayo ukuze kuqondwe uhlobo lwezifo zamathambo nezamalunga futhi bathole okuhlosiwe kokwelapha. UDkt Hayata uxhumene nezinhlangano eziningana zaseJapan kanye ne-American Society for Bone and Mineral Research. Ushicilele izindatshana zokuqala ezingaphezu kuka-50 futhi wanikeza izethulo ezingaphezu kuka-150 ezingqungqutheleni zezemfundo. Ngaphezu kwalokho, ucwaningo lwakhe nge-osteoporosis luye lwafinyelela emaphephandabeni aseJapane izikhathi eziningana.
Imininingwane yokuxhasa ngezimali
Lolu cwaningo lusekelwe yi-JSPS KAKENHI [inombolo yesibonelelo 18K09053]; Nanken-Kyoten, TMDU (2019); iNakatomi Foundation; Ukusekela Ucwaningo lwe-Astellas; I-Pfizer Academic Contribution; I-Daiichi-Sankyo Academic Contribution; I-Teijin Pharma Academic Contribution; Eli Lilly Japan Igalelo Lezemfundo; I-Otsuka Pharmaceutical Academic Contribution; Shionogi Academic Contribution; I-Chugai Pharmaceutical Academic Contribution.
