Masayendisiti anotsanangura basa reimwe puroteni muchizvarwa chemasero akakosha kugadziriswa kwemapfupa
Zvirwere zvepfupa uye zvekubatana, zvakaita se osteoporosis uye rheumatoid arthritis, zvinokanganisa mamirioni avanhu pasirese, kunyanya vakwegura, vachidzikisira hupenyu hwavo. Chinhu chakakosha muzvirwere zvese izvi kuita kwakanyanyisa kwemapfupa-ekuparadza maseru anonzi osteoclasts. Osteoclast anoumbwa kuburikidza nemusiyano kubva kune imwe mhando yesero rekudzivirira muviri inonzi macrophage, mushure maizvozvo vanowana yavo nyowani basa mukuchengetedza kwemapfupa nemajoini: kutyora pfupa nyama kubvumira maosteoblast - rumwe rudzi rwesero - kugadzirisa uye kugadzirisa maronda .
Zvakawandisa, maviri epamukati maseru maitiro anobatanidzwa mukusiyanisa uku: chekutanga, kunyora-uko mutumwa RNA (mRNA) inogadzirwa kubva kune iyo ruzivo ruzivo muDNA - uyezve, dudziro - mune iro ruzivo mune mRNA yakatemwa kuti ibudise mapuroteni ayo ita zvakasarudzika musero. Kubva zvakawanikwa zveimwe puroteni inonzi RANKL muosteoclast fomati, masayendisiti akagadzirisa chikamu chakakura chepuzzle iyo maseru ekuratidzira nzira uye zvinyorwa zvemanyorerwo zvinodzora chizvarwa cheosteoclast. Asi, epashure-kudhindwa maseru maitiro akabatanidzwa anoramba achinzwisiswa.
Zvino, muchidzidzo chitsva chakaburitswa muBiochemical uye Biophysical Research Kutaurirana, vesaenzi paTokyo University yeSainzi, Japan, vakaburitsa chinzvimbo cheprotein inonzi Cpeb4 mune ino yakaoma maitiro. Cpeb4 chikamu che "cytoplasmic polyadenylation element inosunga (CPEB)" mhuri yemapuroteni, ayo anosunga kuRNA uye nekugadzirisa kushandurwa kwekushandurwa uye kudzvinyirira, pamwe ne "mamwe masplication" maitiro anogadzira mapuroteni akasiyana. Dr Tadayoshi Hayata, avo vaitungamira ongororo iyi, vanotsanangura kuti: “Mapuroteni eCPEB ane chekuita nehurongwa hwakasiyana-siyana hwezvirwere nezvirwere, zvakaita sehutachiona, gomarara, uye musiyano wemasero matsvuku eropa. Zvisinei, mabasa avo mukusiyanisa osteoclast haana kunyatso kuzivikanwa. Naizvozvo, takaita ongororo yakateedzana kuratidza protein kubva kumhuri iyi, Cpeb4, tichishandisa maseru tsika yemakonzo macrophages. ”
Mune akasiyana masero etsika tsika akaitwa, mbeva macrophages akakurudzirwa neRANKL kumutsa kusiyanisa osteoclast uye shanduko yetsika yakaongororwa. Kutanga, vesaenzi vakaona kuti Cpeb4 gene expression, uye zvichidaro huwandu hweCpeb4 protein, yakawedzera panguva yekusiyaniswa kweosteoclast. Zvino, kuburikidza ne immunofluorescence microscopy, vakafungidzira shanduko munzvimbo yeCpeb4 mukati memasero. Vakaona kuti Cpeb4 inofamba ichibva kune cytoplasm ichienda mu nuclei, ichiratidzira maumbirwo chaiwo (maosteoclast anowanzobatanidza pamwechete uye kugadzira maseru ane akawanda nuclei). Izvi zvinoratidza kuti mashandiro eCpeb4 ane hukama neosteoclast kusiyanisa anogona kunge akaitwa mukati memukati.
Kuti unzwisise kuti kukurudzira kweRANKL kunokonzeresa sei kuchinja kweCpeb4 iyi, masayendisiti akasarudza "kudzivisa" kana kudzvinyirira mamwe emapuroteni anova anobatanidzwa "murwizi" munzira dzekutaridza maseracellular dzakakonzerwa nekusimudzira. Vakacherekedza nzira mbiri dzichidikanwa pakuita uku. Kunyange zvakadaro, kumwe kuyedza kuchazodiwa kuti udzidze zvizere nezve kutevedzana kwezviitiko zvinoitika uye ese mapuroteni anobatanidzwa.
Chekupedzisira, Dr Hayata nechikwata chake vakaratidza kuti Cpeb4 inonyanya kukosha kuti osteoclast kuumbwa vachishandisa macrophage tsika umo Cpeb4 yaipererwa. Iwo maseru mune aya tsika haana kuita kumwe kusiyaniswa kuve maosteoclasts.
Zvakatorwa pamwechete, mhedzisiro idombo rekutsika kuti unzwisise nzira dzemaseru dzinobatanidzwa mukuumbwa kweosteoclast. Dr Hayata vanoti: "Chidzidzo chedu chinojekesa basa rakakosha reRNA-inosunga protein Cpeb4 seye" anokurudzira "musiyano weosteoclast. Izvi zvinotipa kunzwisiswa kuri nani kwehurwere hwehutachiona uye hwemajoini hutachiona uye zvinogona kubatsira mukuvandudzwa kwenzira dzekurapa kwezvirwere zvakakura senge osteoporosis uye rheumatoid arthritis. ” Ndinovimba, iyo yakadzika nhanho yekunzwisisa kweosteoclast chizvarwa chakafambiswa neichi chidzidzo pakupedzisira chinozoshandura mukuvandudza hupenyu hwevanhu vanorarama nemapfupa anorwadza uye akabatana zvirwere.
Nezve iyo Tokyo University yeSainzi
Tokyo University yeSainzi (TUS) yunivhesiti inozivikanwa uye inoremekedzwa, uye yakakura sainzi-yakasarudzika yakazvimirira yekutsvagisa yunivhesiti muJapan, ine makampasi mana ari pakati peTokyo nemasabhabha ayo uye muHokkaido. Yakagadzwa mu1881, iyo yunivhesiti yakaramba ichipa mukusimudzira kweJapan musainzi kuburikidza nekudzidzisa rudo rwesainzi mune vaongorori, mahunyanzvi, uye vadzidzisi.
Nebasa re "Kugadzira sainzi uye tekinoroji kune inoenderana kukura kwehunhu, vanhu, uye nzanga", TUS yaita hwakawanda hwekutsvagisa kubva kune yakakosha kune yakashandiswa sainzi. TUS akagamuchira nzira multidisciplinary kutsvakurudza uye akaita nyanyisa kudzidza mune mamwe anokosha minda yanhasi. TUS ndeyekuremekedza uko kwakanakisa musainzi kunozivikanwa nekurerwa. Ndiyo chete yunivhesiti yakazvimiririra muJapan iyo yakaburitsa weNobel Prize anokunda uye yega yega yunivhesiti muAsia kugadzira Nobel Prize vanokunda mukati mesainzi sainzi munda.
Nezve Mubatanidzwa Muzvinafundo Tadayoshi Hayata anobva kuTokyo University yeSainzi
Kubva 2018, Dr Tadayoshi Hayata vanga vari Associate Professor uye Principal Investigator kuDhipatimendi reMolecular Pharmacology, Ruzivo rweFarmaceutical Science, kuTokyo University yeSainzi. Rabhoritari yake inotarisa pane bone metabolism, kupatsanura kwemaseru, mamorekuru pharmacology, uye mamwe masango akafanana kuti anzwisise chimiro chehosha uye akabatana zvirwere uye nekuwana marapirwo. Dr Hayata vanobatana neanoverengeka maJapan Masangano uye iyo American Society yeBone uye Mineral Research. Akaburitsa pamusoro pezvinyorwa makumi mashanu zvekutanga uye akapa zvinopfuura zana nemakumi mashanu emitambo mumisangano yezvidzidzo. Uye zvakare, kutsvagurudza kwake nezve osteoporosis kwakakuita kumapepanhau eJapan kanoverengeka.
Ruzivo rwemari
Ichi chidzidzo chakatsigirwa naJSPS KAKENHI [Grant nhamba 18K09053]; Nanken-Kyoten, TMDU (2019); iyo Nakatomi Foundation; Astellas Kutsvaga Kutsigira; Pfizer Yedzidzo Mupiro; Daiichi-Sankyo Yedzidzo Mupiro; Teijin Pharma Yedzidzo Mupiro; Eli Lilly Japan Yedzidzo Kubatsira; Otsuka Pharmaceutical Dzidzo Yekupa; Shionogi Yedzidzo Mupiro; Chugai Pharmaceutical Dzidzo Yekupa.
