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▎ Wetin na Teriparatid?
Teriparatid na rεkombinεnt hכman paratayroyd כmon (PTH) analכg we kכmכp fכ di fכs 34 amino asid dεm fכ di hכman paratayroyd כmon. i de rεgεl di bon mεtabolism bay we i de miks di fysiolojikal akshכn dεm we di εndojεnik paratayroyd כmon de du. Teriparatid na di fכs sεntetik anabolik dכg we dεn apruv fכ siriכs כstioporosis. in strכkchכ de sho hכy homכli wit εndojεnik PTH, we de mek aktibכshכn fכ di PTH rεsεpכta fכ mכdulet כsteoklast mεtabolik aktiviti.
▎ Tɛriparatid Strukchɔ
Sos: PubChem |
Sikyɔn: SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF Mɔlikul Fɔmula: C 181H 291N 55O 51S2 Molekyula Weyt: 4118 g/mol CAS Nɔmba: 52232-67-4 PubChem CID:16133850. Di wan dɛn we de wok Di tin dɛn we gɛt di sem minin: Teriparatida; Tɛriparatidɔm we dɛn kɔl; 1-34-Mɔtalman PTH |
▎ Tɛriparatid Risach
Wetin na di difinishɔn fɔ Teriparatid?
Teriparatid na rεkombinεnt hכman paratayroyd כmon (PTH) analכg we kכmכp fכ di fכs 34 amino asid dεm fכ di hכman paratayroyd כmon. i de rεgεl di bon mεtabolism bay we i de miks di fysiolojikal akshכn dεm we di εndojεnik paratayroyd כmon de du. Teriparatid na di fכs sεntetik anabolik dכg we dεn apruv fכ siriכs כstioporosis. in strכkchכ de sho hכy homכli wit εndojεnik PTH, we de mek aktibכshכn fכ di PTH rεsεpכta fכ mכdulet כsteoklast mεtabolik aktiviti.
Wetin na di mɛkanism fɔ akshɔn fɔ Teriparatid?
Ifekt dεm pan כstioblast dεm:
i de mek di osteoblast proliferashכn: di teriparatid de mek di osteoblast prεkursכr sεl dεm proliferashכn, we de mek di osteoblast nכmba dεm go כp. insay animal stכdi dεm, intamitεnt administreshכn fכ teriparatide sכmtεm aksεlεrayt di proliferashכn fכ mεsenchymal stεm sεl dεm we ebul fכ difrεnt insay כsteoblast dεm na bon mכro. dis mek mכr sεl dεm fכ difrεnt to machכ כstioblast dεm, we de gi bכku sεl saplai fכ bon fכmeshכn. in vitro sel kכlt εkspεriεns dεn sho se di divεlכpmεnt rεt fכ di כsteoblast prεkursכr sεl dεm na di Teriparatid-trit grup bin sכmtεm hכy pas di kכntrol grup, we sho se Teriparatid de protεkt di proliferashכn fכ di כsteoblast prεkursכr sεl dεm [1,2]..
εnhans כstioblast Aktiviti: Tεriparatid nכ de כnli inkrεs di כstioblast nכmba bכt i de εlevεt dεn aktiviti. i de upregulate di εksprεshכn fכ di jin dεm we de aכsכsiayt wit bon matris sεntez insay כsteoblast dεm, lεk dεn wan dεm we de kכd tayp I kolagen εn osteocalcin, we de sho signifyant inkrεs εksprεshכn lεvεl dεm. di tayp I kolagen, di praymar כrganik kכmכpכnt fכ di bon matris, de kכntribyut fכ fכm wan mכr rכbכst matris fכm tru inkrεs sεntesis. כsteokalsin de ple imכtant rol fכ bon minralayzεshכn bay we i de protεkt kalsiכm ayכn dεposishכn insay di matris, we de mek di bon minralayzεshכn bכku. tru dεn mεkanism dεm ya, di כstioblast dεm de sכntez εn sekret bon matris mכr efyushכn, we de mek nyu bon fכmeshכn izi [2,3]..
inhibishכn fכ di osteocyte apoptosis: כnda nכmal fysiolojikal kכndishכn dεm, di osteocytes de כnda apoptosis afta dεn dכn komplit spεsifi k bon fכmeshכn wok dεm. di tεriparatid de sכpres dis apoptotik prכsεs, we de mek di כstiosayt layfspan lכng. di teriparatid de aktibכt di rilevεnt sεlyul signal path dεm, lεk di PI3K/Akt path. we dεn aktibכt, dis path de sכpres di εksprεshכn fכ di apoptosis-rεlatεd protin dεm, we de mek כstioblast dεm fכ sכstayn dεn bon fכm fכnshכn dεm εn mεnten di kכntinyu εn stεbiliti fכ di bon fכmesh כn [1,3]..
di ifekt dεm pan di כstioklast dεm: di ifekt dεm we teriparatid de du pan di כstioklast dεm na kכmpleks. di tεm we dεn de gi dכz intamitεnt, i de infכlכw di כsteoklast dεm tru indaykt mεkanism dεm. i de promuot osteoblast sekreshכn fכ osteoprotegerin (OPG), we na saytokכn we kכmpεtitivli biεn di rεsεpכta aktibכt fכ nyuklia fכktכ κB ligεnd (RANKL). RANKL na di kכl rεgεlεt fכ di כsteoklast difrεns εn aktibכshכn. we OPG de biεn RANKL, RANKL nכ kin ebul fכ biεn di RANK rεsεpכta na di sεf fכ di כsteoklast prεkursכr sεl dεm, we de mek di כsteoklast difrεns εn machכ εn rεdכks di bon rεsכpshכn. pan כstioporosis pasεnshכn dεm, usay di bon rεsכpshכn pas fכmeshכn we de mek di bon dεm lכs, teriparatide de ridyus di כstioklast aktiviti tru dis mεkanism. dis de mek bεlε bak bitwin rεsכpshכn εn fכmeshכn, we de mek di bon gεt [2,3]..

Figure 1 Sayt dεm fכ akshכn fכ fכs layn כstioporosis tritmεnt dεm. Teriparatid, we na wan rεkombinεnt fragmεnt fכ di paratayroyd כmon, de mek di bon fכmeshכn bay we i de inkrεs di כstioblast aktiviti εn, to sכm sכm, i de inhibit di כstioklast rikrutmεnt [4]..
Modulation of Bon Mεtabolism-Rεlatεd Sayn Pathways:
Wnt/β-Catenin Signaling Pathway: di Wnt/β-catenin signal pathway de ple imכtant rol fכ di bon divεlכpmεnt εn mεntenans fכ bon homכstasis. teriparatid de aktibכt dis path, we de protεkt intasεlulyar akyumyuleshכn εn nyuklia translכkeshכn fכ β-catenin. nyuklia β-catenin de biεn to asosiet transkripshכn fכktכ dεm, we de initiate transkripshכn fכ bon fכmeshכn-rεlatεd jin dεm εn εnhans εksprεshכn fכ di כsteoblast-spεsifi k transkripshכn fכktכ Runx2. Runx2 de rεgεl di כsteoblast difrεns εn fכnshכn mכr, we de mek di bon fכmeshכn. aktibכshכn fכ dis path de inhεbit כsteoblast difrεns to di adiposyt dεm, we de mek sכh se di bon mכro mεsenchymal stεm sεl dεm de difrεnt to di כstioblast laynej, we de mek di bon mas inkrεs [1,3]..
PTH/PTHrP Risεptor Signaling Pathway: Teriparatid, we na wan analכg fכ paratayroyd כmon (PTH), de fכs fכ du in ifekt dεm bay we i de biεn di PTH/PTHrP rεsεpכta. we i biεn, Teriparatid de aktibכt dכwnstrim signal path dεm lεk di cAMP/PKA path εn di PLC/PKC path. di aktibכshכn fכ dεn path dεm ya de rεgεl di כstioblast εn כsteoklast fכnshכn, we de protεkt di bon fכmeshכn. di cAMP/PKA path de εnhans εksprεshכn fכ כsteoblast-rεlatεd jin dεm bay we i de mכdulet transkripshכn fכktכ aktvכti, we di PLC/PKC path de infכlכw saytoskelεtal riכganayzεshכn εn sεl mכtiliti, we de afekt כsteoblast maygrεshכn εn fכnshכn [2,5]..
Wetin na di aplikeshɔn dɛn fɔ Teriparatid?
Ɔstioporosis Tritmɛnt fɔ di sik
Postmenopausal Osteoporosis: Teriparatid na di fכs sεntetik anabolik ejen we dεn apruv fכ trit uman dεm we gεt postmenopausal we gεt siriכs כstioporosis. bay we i de mek di bon fכmeshכn, i de mek di bon mas bכku, we de mek i rεdכks di risk fכ brok. pan uman dεm we dεn pas mεnopauz, we dεn yuz teriparatide evride de inkrεs di bon minral dεnsiti, we de ridyus di risk fכ vεrbral frakshכn bay 65% εn nכn vεrbral fragiliti frakshכn bay 53% we yu kכmpεr wit plasεbo. Wan mεta-analysis fכ individyual pasεnt-lεvεl data sho 56% rεdukshכn pan hip frakshכn risk kכmpεr to kכntrol. pan tap dat, we yu kompare to risedronate, Teriparatid ridyus di risk fכ nyu vεrbral εn klinik frakshכn bay 56% εn 52%, rispεktivli, pan uman dεm we gεt siriכs כstioporosis [3,6,7]..
Man ɔstioporosis: Dɛn dɔn gri fɔ am bak fɔ trit man ɔstioporosis. Quattrocchi E ɛn ɔda pipul dɛn. dεn sho se insay man כstioporosis pasεnshכn dεm, Teriparatid (20μg εn 40μg de injεkshכn) prodyuz stεdi sכmtin inkrεs pan lכmba spayna bon minral dεnsiti: 5.9% insay di 20μg grup εn 9.0% insay di 40μg grup (dεn tu P < 0.001). na di fεmoral nεk, di bon dεnsiti inkrεs bay 1.5% insay di 20μg grup (P = 0.021) εn bay 0.9% insay di 40μg grup (P < 0.001) [7]..
Glucocorticoid-Associated Osteoporosis: Dɛn kin yuz teriparatid bak fɔ trit glucocorticoid-induced osteoporosis pan man ɛn uman pasɛnt dɛn we gɛt fraktrɔs, we kin ɛp dɛn sik pipul ya fɔ mek dɛn bon bɔku ɛn ridyus di bon we de lɔs ɛn frakt risk we gɛt fɔ du wit glucocorticoid yus [8]..
Frakshכn Hilin Sכpכt: fכ frakshכn pasεnshכn dεm, fכ transiεntli inkrεs di bon fכmeshכn na di frakshכn sayt na imכtant fכ ripa, wan rol we teriparatide kin fulfil. Dɛn dɔn stɔdi am pan ɔl tu di animal mɔdel ɛn pasɛnt dɛn as pɔtɛnɛshɛl ɛjɛn fɔ ɛp fɔ mek di fraktrɔs wɛl. Pan ɔl we dɛn nid fɔ du mɔ risach, di ɛksplɔrɔshɔn dɛn we dɔn de de sho se i ebul fɔ mek di fraktrɔs wɛl [3] ..
Alveolar Bone Regeneration: Rilat stכdi dεm sho se Teriparatid kin aplay fכ alveolar bon rigεnεreshכn insay kכndishכn dεm lεk jawbone nεkrכsis, krכnik periodontitis, dental implant osseointegration, εn כtodontik tut muvmεnt, usay i de εnhans di alveolar bon fכmeshכn. כltu, fכda hכman klinik trial dεm nid fכ validet in aplikεshכn εn advεs ifekt dεm across difrεn כral bon sik dεm [9]..
Bεlε εn Laktashכn-Rεlatεd כstioporosis: Insay di sik pipul dεm we gεt bεlε- εn laktashכn-rεlatεd כstioporosis (PLO), tritmεnt wit Teriparatid (20μg/de) we dεn kכmbayn wit kalsiכm εn vaytam in D rεsult in signifyant big inkrεs pan di lכmba spayna bon minral dεnsiti na 12 εn 24 mכnt kכmpεr to kalsiכm εn vaytam in D nכmכ. na 12 mכnt, di min inkrεs pan di lכmbar spayna bon minral dεnsiti na bin 20.9 ± 11.9% in di teriparatide grup vεrs 6.2 ± 4.8% in di kכntrכl grup ( P < 0.001). na 24 mכnt, di min inkrεs pan lכmbar spayna bon minral dεnsiti na bin 32.9 ± 13.4% in 7 pasεnshכn dεm we dεn trit wit Teriparatid εn 12.2 ± 4.2% in 6 kכntrol pasεnshכn dεm ( P = 0.001). Nɔ nyu klinik fraktrɔs nɔ bin apin we dɛn bin de trit am [10]..
Spɛshal Aplikeshɔn: Dɛn dɔn ripɔt teriparatid insay kes stɔdi fɔ spɛshal bon dizayd, lɛk haypoparatayroydism-asɔsiet ɔstiɔdistrofi (ABD) wit haypa kalsiɔm. Wan uman we ol 51 ia we de dipεnd pan dayalaysis bin divεlכp haypakalsimia pכst-paratayroydεktכmi, we dεn kכnfכm bay bon bayopsi as ABD. afta 12 mכnt we di Teriparatid tritmεnt, di sεrum kalsiכm lεvεl dεm nכmal, we riprizent di fכs dכkument kes fכ Teriparatid we de rεsכlv ABD-rεlatεd haypakalsiכm [11]..
Dɔn
Teriparatid de wok fayn fɔ siriɔs ɔstioporosis wit ay fraktrɔs risk. I de sho fɔ pasɛnt dɛn we gɛt histri bɔt bɔku ɔstioporotik fraktrɔs, we gɛt bɔku bɔku bon minral dɛnsiti, ɛn we nɔ gɛt bɛtɛ rispɔns to kɔvɛnshɔnal ɔstioporosis tritmɛnt dɛn.
Bɔt di pɔsin we rayt di buk
Di tin dɛn we wi dɔn tɔk bɔt, na ɔl di tin dɛn we Cocer Peptides dɔn du risach, ɛdit ɛn kɔmpilayt.
Sayɛns Jɔnal Author
Suzan V. Bukata na risachman na di Yunivasiti ɔf Rɔchɛsta Skul fɔ Mɛdisin ɛn Dɛntis, we spɛshal pan ɔtpidik ɛn mɔskul skel sik dɛn. I dɔn kɔ-ɔda bɔku buk dɛn we de pe atɛnshɔn pan bon bayoloji, fraktrɔs hilin, ɛn di klinik aplikeshɔn fɔ anabolik ɛjɛn lɛk teriparatide insay ɔtpidik prɛktis. In wok dɔn ɛp fɔ ɔndastand di tritmɛnt strateji fɔ ɛp fɔ mek di bon dɛn ripɛnt ɛn fɔ mek dɛn gɛt nyu bɔdi bak. Suzan V. Bukata de na di list insay di rɛfrɛns fɔ saytayshɔn [1].
▎ Saytayshɔn dɛn we gɛt fɔ du wit dis
[1] Bukata S. V., Puzas J. E., ɛn ɔda pipul dɛn. Ɔtpidik yus dɛm fɔ teriparatide. Kɔrɛnt Ɔstioporosis Ripɔt dɛn 2010; 8(1): 28-33.DOI: 10.1007/s11914-010-0006-3.
[2] Hasegawa T, Miyamoto Y, Yamamoto T, Amizuka N. [Anabolik akshɔn fɔ teriparatide to ɔstioporotik pasɛnt dɛn]. Nihon Yakurigaku Zasshi 2019, ɛn di ɔda wan dɛn; 153(1): 16-21.DOI: 10.1254/fpj.153.16.
[3] Marin F, Ma Y L., ɛn ɔda pipul dɛn. Ostioporotik Frakshכn εn Sεstεmik Skel Dizכrd: Mεkanism, Asesmεnt, εn Tritmεnt. In: Takahashi H. E., Burr D. B., Yamamoto N, eds. Teriparatid we gɛt di sik. Singapɔ: Springer Singapɔ; 2022: 339-359.DOI: 10.1007/978-981-16-5613-2_22.
[4] Hanley D, Adachi J, Bell A, Brown V. Denosumab: Mεkanism fכ akshכn εn klinik autkam. Int ɛ rnash ɔ nal J ɔ rnal ɔ f Klinik Pr ɛktis 2012; 66.DOI: 10.1111/ijcp.12022. Di wan dɛn we de stɔdi bɔt di Baybul.
[5] Kim S. Mɛkanism ɛn ɛfifikɛshɔn fɔ paratayrɔyd ɔmon insay ɔstioporosis. Jɔnal fɔ di Korian Mɛdikal Asɛmbli 2022; 65: 361-365.DOI: 10.5124/jkma.2022.65.6.361.
[6] Stroup JS, Kane MP, Abu-Baker A. Teriparatid in di tritmɛnt fɔ ɔstioporosis. Amɛrikan Jɔnal fɔ Wɛlbɔdi-Sistem Famasi : Ajhp : Ɔfishal Jɔnal fɔ di Amɛrikan Sɔsayti fɔ Wɛlbɔdi-Sistem Famasis 2008; 65 6: 532-539. Di s://api.semanticscholar.org/KɔpɔsID:207290777. Di wan dɛn we de stɔdi bɔt di Baybul.
[7] Quattrocchi E, Kourlas H. Tɛriparatid: wan rivyu. Klinik Tɛrapi 2004; 26 6: 841-854, ɛn ɔda pipul dɛn. https://api.semanticscholar.org/CorpusID:20011673, di wan dɛn we de stɔdi bɔt di Baybul.
[8] Minisola S, Cipriani C, Grotta GD, ɛn ɔda pipul dɛn. Update pan di sef ɛn ɛfifikɛshɔn fɔ teriparatide fɔ trit ɔstioporosis. Tεrapi Advans in Mכskuloskelεtal Disiz 2019;DOI: 10.1177/1759720X19877994.
[9] Agnihotri R, Gaur S. Aplikeshɔn fɔ Teriparatid fɔ Alveolar Bɔn Rijɛnɛreshɔn: Wan Sistɛm Rivyu. Jɔnal fɔ Intanɛshɔnal Sɔsayti fɔ Prɛvɛntiv ɛn Kɔmyuniti Dɛntis 2021; 11(6): 639-643.DOI: 10.4103/jispcd.JISPCD_169_21.
[10] Lampropoulou-Adamidou K, Trovas G, Triantafyllopoulos I. K., ɛn ɔda pipul dɛn. Teriparatid Tritmεnt in Pasεnt dεm wit Bεlε- εn Laktashכn-Asכsiet כstioporosis. Kalsifayd Tisu Int ɛ rnash ɔ nal 2021; 109(5): 554-562.DOI: 10.1007/s00223-021-00871-y.
[11] Peugh J, Khalil A, Chan M. R., Hansen K. E., ɛn ɔda pipul dɛn. Teriparatid Tritmɛnt fɔ Hypercalcemia we gɛt fɔ du wit Adynamic Bone Disease. Jbmr Plɔs 2019; 3(7): e10176.DOI: 10.1002/jbm4.10176.
ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN ƐN FƆ EDYUKESHƆN.
Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto famasitik, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.