Puas yog 7,8-dihydroxyflavone Puas Siv Tau Rau Kev Txhim Kho Pob Txha?

Pob txha yog cov ntaub so ntswg dynamic thiab hloov kho tas li uas tau hloov pauv tseem ceeb thoob plaws hauv nws lub neej. Kev kho pob txha integrates osteoblast mediated pob txha tsim thiab osteoclast mediated pob txha resorption, nrog rau cov pob txha hlwb nyob rau hauv cov pob txha matrix thiab osteoblast derived hauv ob sab phlu hlwb uas npog cov pob txha nto. Kev cuam tshuam qhov sib npaug ntawm cov pob txha resorption thiab kev tsim cov pob txha tuaj yeem ua rau cov kab mob pob txha xws li pob txha pob txha, ntau yam myeloma, thiab osteopetrosis.

Ntau yam tseem ceeb muaj feem cuam tshuam rau kev tswj cov pob txha. Nws tau raug pov thawj tias lub hlwb tau txais txiaj ntsig neurotrophic (BDNF) tuaj yeem txhawb nqa kev sib txawv ntawm osteoblast, tsiv teb tsaws, thiab kho pob txha. BDNF yog ib tug tswv cuab ntawm tsev neeg neurotrophic uas tswj ntau yam kev lom neeg los ntawm kev khi rau transmembrane receptor tyrosine kinase B (TrkB). Txawm li cas los xij, TrkB teeb liab tshwm sim los ntawm BDNF yog lub teeb liab hloov pauv ntawm 10 feeb thiab lub siab tshaj plaws ntawm 60 feeb. Txawm li cas los xij, BDNF muaj ib nrab-lub neej luv luv thiab tsis yooj yim rau hla cov hlab ntsha hauv hlwb. Cov txiaj ntsig ntawm ntau qhov kev sim tshuaj uas siv cov recombinant BDNF kuj tau poob siab, tej zaum yog vim qhov luv luv hauv vivo ib nrab lub neej thiab kev xa khoom tsis zoo ntawm BDNF. Cov kev tsis txaus no ua rau muaj kev cuam tshuam tsis zoo rau kev siv tshuaj kho mob ntawm BDNF. 7,8-dihydroxyflavone (7,8-DHF) yog cov nroj tsuag muab tau los ntawm flavonoid uas tuaj yeem kov yeej cov kev txwv saum toj no ntawm BDNF thiab tau raug txheeb xyuas tias ua haujlwm BDNF mimetic. Nws tau raug pom nyob rau hauv ntau yam biochemical thiab cellular systems uas nws muaj peev xwm induce TrkB dimerization thiab qhib nws downstream signaling molecules.

Txawm li cas los xij, tuaj yeem 7,8-DHF ua haujlwm raws li kev tswj hwm ntawm cov pob txha kho thiab ua lub luag haujlwm tiv thaiv pob txha; Puas yog TrkB mediate 7,8-DHF-induced osteogenesis thiab Wnt/ - Cov txheej txheem ntawm kev cuam tshuam ntawm Catenin signals tseem tsis tau meej meej. Yog li ntawd, tom qab kev sib koom tes kawm ntawm Zhang Ying Laboratory ntawm Lub Tsev Kawm Ntawv ntawm Biosystems Engineering thiab Food Science ntawm Zhejiang University thiab Ye Keqiang Laboratory ntawm Department of Pathology thiab Laboratory Medicine ntawm Tsev Kawm Ntawv Tshuaj ntawm Emory University hauv Tebchaws Meskas, ib daim ntawv tshawb fawb. npe "7,8-Dihydroxyflavone modulates pob txha tsim thiab kam rau ua thiab ameliorates ovarionomy-induced Osteoporosis" tau luam tawm nyob rau hauv lub vev xaib ntawm Elife (IF=8.14), Cov teebmeem ntawm BDNF thiab 7,{{12 }}DHF ntawm osteoblast tsim nyob rau hauv cov pob txha progenitor hlwb MC3T3-E1 thiab osteoclast tsim nyob rau hauv RAW264.7 hlwb induced los ntawm RANKL raug soj ntsuam, tshwj xeeb yog elucidate lub molecular mechanism nyob rau hauv lub functionality ntawm 7,8-DHF .

cov kev kawm tau pom tias BDNF thiab 7,8-DHF ob leeg txhawb kev loj hlob, kev sib txawv osteogenic, thiab mineralization ntawm MC3T3-E1 hlwb. Cov teebmeem no yuav raug ntaus nqi los ntawm Wnt / - Ua kom muaj Catenin protein signaling txoj hauv kev vim cyclin D1, p-GSK3 , - Cov lus qhia ntawm Catenin, Runx2, Osterix, thiab OPG tau raug kho kom zoo. - Lub khob tawm ntawm Catenin inhibits lub upregulation ntawm Runx2 thiab Osterix stimulated los ntawm 7, 8-DHF. Hauv particular, nws cov inhibitor tshwj xeeb K252a thaiv TrkB los ntawm inhibiting 7, 8-DHF-induced osteoblast proliferation, sib txawv, thiab osteogenic noob qhia. Ntxiv rau, BDNF thiab 7,8-DHF inhibit osteoclast sib txawv hauv RAW264.7 hlwb. Cov kev hloov pauv c-fos thiab osteoclast noob xws li tartrate resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9), thiab Adamts5 yog inhibited los ntawm 7,8-DHF. Qhov tseem ceeb tshaj, hauv ovariectomized (OVX) nas qauv, 7, 8-DHF tuaj yeem txo cov pob txha poob, txhim kho pob txha trabecular microstructure, tibial biomechanical zog, thiab cov pob txha biochemical ntsuas. Cov kev tshawb fawb tam sim no qhia txog qhov kev tswj hwm ntawm ob txoj cai ntawm 7,8-DHF ntawm kev kho pob txha.