Methylene blue nekuchembera kwemapfupa: nei zvakawanikwa mumasero zvisina kufanotaura zvakaitika kumapfupa embeva

Fungidzira chinhu chemakemikari chinodzikamisa masero chaiwo anodya pfupa, chichiedzwa mundiro yemurabhoritari uye chichishanda sezvaitarisirwa. Maosteoclast ane nuclei dzakawanda anova mashoma, mhinduro yacho inosiyana zvakajeka zvichienderana nedosi, uye pane tsananguro inonzwisisika inosanganisira mitochondria. Zvadaro chinhu chimwe chetecho chinopiwa mbeva kwenguva zhinji youpenyu hwadzo dzakura, mapfupa adzo oongororwa nemifananidzo inoratidza mativi matatu, asi hapana chinosiyana. Mapfupa akwegura anoramba achiratidza kuchembera, angave akapiwa chinhu ichocho kana kuti asina.

Ndizvo chaizvo zvakabuda mune imwe tsvakiridzo ya2024, uye zvakakosha kunyatsonzwisisa izvi, nokuti ndipo panoputsika zvakawanda zvinotaurwa pamusoro pezvinowedzerwa pakudya zvemapfupa. Chinyorwa chacho ndechaPoudel nevamwe vake, chakabudiswa muAging muna March 2024, uye chinowanikwa pachena, saka chiyero chega chega chiri pasi apa chinogona kuenzaniswa nechinyorwa chekutanga. Chinonyanya kubuda machiri ndechekuti hapana musiyano wakawanikwa. Kuwana pasina musiyano hakusi kukundikana. Imhinduro, uye iyi inopindura mubvunzo wakanyatsoganhurirwa zvakanaka: kupa methylene blue kana mitoquinone kwenguva refu semishonga inodzivisa oxidation mumuviri wose kunochengetedza mapfupa embeva ari kuchembera here? Kwete.

Kuchembera kwemapfupa kunoratidzika sei munhamba

Kurasika kwemapfupa nekuda kwezera hakusi chinhu chimwe chete, saka tsvakiridzo haina kuyera chinhu chimwe chete. Vachishandisa micro-computed tomography, vaongorori vakatora mifananidzo yenzvimbo nhatu dzemapfupa: cortical bone pakati pechikamu chakareba chefemur, pfupa rechidya (chikamu chakabatana uye chakasimba), trabecular bone pametaphysis iri kumucheto wezasi wefemur (mambure akaita sesiponji ari pedyo nejoini), uye trabecular bone muvertebra yechishanu yekuzasi kwemusana. Panzvimbo imwe neimwe vakanyora zviyero zvinowanzo shandiswa kutsanangura maumbirwo madiki emapfupa. BV/TV chikamu chevhoriyamu chine pfupa panzvimbo penzvimbo yemwongo. BMD kuwanda kwezvicherwa pavhoriyamu. Tb.Th, Tb.N, uye Tb.Sp zvinotsanangura ukobvu, nhamba, uye mipata iri pakati pematanda madiki etrabecular bone. Ukobvu hwecortical bone nenzvimbo dzinoyerwa kana pfupa rachekwa richiyambuka zvinotsanangura chikamu chakareba chepfupa.

Funga nezvetrabecular bone sechirongwa chematanda anotsigira mukati meimba yekuchengetera zvinhu. Kuchembera kunobvisa mamwe matanda zvachose uye kunotetepa asara, saka chikamu chenzvimbo chakazadzwa nechirongwa ichi chinoderera, matanda asara anenge ave kure kure nerimwe, uye chirongwa chose chinokwanisa kutakura mutoro muduku. Cortical bone ndiyo madziro eimba yekuchengetera zvinhu, ayo ari kuramba achitetepa. Kurapa kunodzivirira mapfupa kunofanira kuoneka munhamba idzi. Ndiwo muedzo wakashandiswa netsvakiridzo iyi.

Zvakaitika mundiro yemurabhoritari

Ongororo yemasero yakashandisa mwongo wakatorwa mumafemur nematibia, mapfupa ezvidya neemakumbo ezasi, embeva dzeUM-HET3 dzaiva nemwedzi 6 kusvika 7. Urwu rudzi rwembeva rune kusiyana kwemajini, rwakaberekeswa kuti rushandiswe mukutsvakurudza kuchembera. Pakabuda zvinhu zvina, uye zvinonongedzera kumativi akasiyana, saka chimwe nechimwe chinoda kutsanangurwa pacho.

Chekutanga, mesenchymal stem cells, boka rinosanganisira masero anozova masero anovaka mapfupa, akaramba ari mapenyu pamwero yemethylene blue nemitoquinone kubva pa0.125 kusvika pa0.5 micromolar kwemaawa 48. Hapana kukuvadzwa kwemasero, hapana kuwedzerwa kwekurarama kwawo. Chechipiri, apo stem cells idzodzo dzakakurudzirwa kuva maosteoblast mumushonga unokurudzira kuumbwa kwepfupa, ndokupendwa kuti paonekwe alkaline phosphatase pazuva 18, hapana chimwe chezvinhu zviviri izvi chakachinja zvakabuda pamwero upi zvawo wakaedzwa. Chikamu chinovaka pfupa mundiro hachina kupindura.

Chechitatu, chikamu chinoputsa pfupa chakapindura. Masero emwongo anotangira maosteoclast, akakurudzirwa neM-CSF neRANKL, nzira inowanzo shandiswa kugadzira maosteoclast, akaumba masero mashoma ane nuclei dzakawanda uye anoratidza TRAP sezvo mwero waikwira. Kuderedzwa kwakajeka kwakaonekwa pamusoro pe0.25 micromolar, kureva pamwero wepamusoro wakaedzwa we0.5. Izvi ndizvo zvinobereka pfupiso dzakawanda dzine tariro, uye ndezvechokwadi mukati memiganhu yazvo: kusangana kwakananga uye kunoramba kuripo pakati pemasero nechinhu ichi murabhoritari kwakadzvinyirira kuumbwa kwemaosteoclast zvichienderana nedosi.

Chechina, maosteoblast akura akaiswa pazvinhu izvi kwemaawa 48 ndokuedzwa kuti mitochondria dzawo dzinoita sei padzinomanikidzwa kushanda. Haana kuratidza musiyano wakakosha pakushandiswa kweoxygen kwekutanga kana kwepamusoro-soro nechimwe chezvinhu zviviri izvi. Pa0.5 micromolar zvose zvaiita sezvinoderedza kufema kwemasero zvishoma, asi shanduko yacho haina kusvika pamwero unonzi wakakosha pakuongorora manhamba. Saka kuedza mundiro hakuna kuratidza kuvandudzwa kwemitochondria mumasero anovaka pfupa kwaigona kuiswa pamwe chete nemhedzisiro yokudzvinyirira maosteoclast. Nzira yakanga yafungidzirwa, yokuvandudza mashandisirwo esimba kuburikidza necheni inotakura maelectron mumitochondria, haina kubudisa kuwedzera kunoyerwa kwekufema kwemasero munzvimbo yaitsvakwa nevaongorori.

Zvakaitika mumbeva

Kuedza kuviri mumhuka kwakazotevera, kuchiitwa pazviyero zvakasiyana zvikuru.

Kuedza kuduku kwakashandisa mbeva hadzi dzeC57BL/6J dzakaberekeswa kubva kuhama dzepedyo, rudzi runonyanya kushandiswa mutsvakiridzo yezvekurapa nehupenyu. Kubva pazera remwedzi 18, rinofanana nekuguma kwezera repakati muupenyu hwebeva, hafu yadzo yakanwa mvura yaiva ne250 micromolar yemethylene blue kwemwedzi 6 kana 12, kusvikira dzava nemwedzi 24 kana 30. Hadzi dzemwedzi 18 dzisina kupiwa mushonga ndidzo dzakashandiswa semamiriro ekutanga ekuenzanisa, uye hadzi dzemwedzi 5 dzakaratidza maitiro emapfupa echidiki. Kuchembera kwakaita chaizvo zvakwagara kuchiita. Muvertebra yeL5, chikamu chevhoriyamu chine pfupa chakaderera neinenge 35 percent, kuwanda kwezvicherwa neinenge 18 percent, uye nhamba yematanda madiki etrabecular bone yakada kusvika pahafu, pasinei nekupiwa mushonga. Ukobvu hwecortical bone hwakaderera neinenge 10 percent pakati pemwedzi 18 ne24 uye neinenge 30 percent pakasvika mwedzi 30. Methylene blue haina kuchinja chero imwe yenzira idzi dzekuderera.

Kuedza kukuru kwakaitwa kuburikidza neNational Institute on Aging Interventions Testing Program, iyo inoedza zvinhu zvinogona kushandiswa pakupindira mumuviri mumbeva dzeUM-HET3, hono nehadzi, panzvimbo nhatu. Methylene blue iri pa28 parts per million muchikafu, uye mitoquinone iri pa100 parts per million, zvakatangwa mbeva dzichangopinda muzera revakuru uye zvakaenderera kusvikira dzava nemwedzi inenge 22 kusvika 24. Nzvimbo nhatu dzemapfupa dzakafanana nedzekutanga dzakaongororwa ne micro-CT. Tafura yakabudiswa inoratidza chiyero chega chega zvichienderana nekuti mbeva ihono kana hadzi uye nezvayakapiwa, iine ongororo yeman hamba yakagadziridzwa. Koramu yezvayakapiwa inotaura chinhu chimwe chete kwese: hapana mhedzisiro yakakosha pakuongorora manhamba, hapana kusiyana kwemhedzisiro yokurapa pakati pehono nehadzi, panzvimbo ipi zvayo. Zvingava cortical kana trabecular bone, femur kana musana, hono kana hadzi, methylene blue kana mitoquinone. Mapfupa akaramba achichembera nenguva yawo.

Tafura inoenzanisa zvikamu zviviri izvi

Iyi ndiyo tafura inovakira chinyorwa chose. Mutsara wega wega unoisa pamwe chete zvakaratidzwa mundiro nezvakaratidzwa mumhuka pamaitiro mamwe chete ehupenyu, uchishandisa zviyero zvetsvakiridzo yacho.

Kana ukaverenga mutsara nemutsara, tafura inobvisa zvinoita sekusawirirana. Imwe chete pamaitiro mana emasero ndiyo yakapindura, uye yakapindura chete pedyo nemwero wepamusoro wakaedzwa pakusangana kwakananga kwakaramba kuripo. Zvimwe zvose mundiro zvakanga zvatova zvisina musiyano. Zvakabuda mumhuka zvino hazvichanyanyi kuita sekupokana, asi sekusimbisa: maitiro matatu asina musiyano pamwe chete nemhedzisiro imwe yaienderana nemamiriro akati mumasero akakuriswa murabhoritari zvakazova kusava nemusiyano pazvose mumhuka.

Maumbirwo emapfupa haasi urefu hweupenyu

Pane kumwe kuvhiringidzika kunoda chikamu chako chega, nokuti methylene blue ine nhoroondo yezvakawanikwa pamusoro peurefu hweupenyu uye zviri nyore kuiverenga zvisizvo sekunge ihumbowo hwemapfupa. Muboka rekare reInterventions Testing Program, methylene blue padosi rimwe chete muchikafu yakawedzera urefu hweupenyu pa90th percentile yehadzi dzeUM-HET3 neinenge 6 percent. Iyi yaiva mhedzisiro yekurarama muchikamu chokupedzisira cheupenyu, pasina shanduko paurefu hweupenyu hwepakati uye pasina mhedzisiro muhono. Mitoquinone haina kuratidza mhedzisiro paurefu hweupenyu muhono kana muhadzi. Nhamba idzodzo dzekurarama dzinobva muzvinyorwa zvechirongwa zvakabudiswa pamusoro peurefu hweupenyu, kwete muchinyorwa chemapfupa.

Zvinounzwa nechinyorwa chemapfupa ndezvekuchengetedza zvinyorwa zviviri izvi zvakaparadzana. Chinhu chemakemikari chinogona kuchinja kurarama muchikamu chokupedzisira cheupenyu muhono kana muhadzi pasina kuchengetedza chero chimiro chemapfupa chakayerwa. Kuyera kurarama kunoverenga kufa kunokonzerwa nezvinhu zvose; micro-CT inoverenga matanda madiki ari muvertebra. Hapana mutemo unoti kupindira kunofanira kushanda kuburikidza nemapfupa kuti kuwedzere upenyu, uye tsvakiridzo iyi ihumbowo hwakananga hwekuti chiratidzo chemethylene blue pakurarama kwehadzi muchikamu chokupedzisira cheupenyu chakafamba neimwe nzira. Munhu anotaura zvakawanikwa paurefu hweupenyu sechitsigiro chemethylene blue neosteoporosis anenge ari kushandisa mari iri mune imwe akaundi isiri iyo. Nzira yokuchengeta humbowo uhwu hwakaparadzana inotsanangurwa mukuverenga tsvakiridzo yemethylene blue.

Nei zvakabuda mundiro zvisina kufanotaura zvakaitika mubeva

Tsananguro shanu dzinoenderana nezvakawanikwa, uye dzinogona kuitika pamwe chete.

Kusangana nechinhu ichi ndiyo yekutanga. Masero akakuriswa murabhoritari akaramba akanyudzwa pamwero yaizivikanwa. Mbeva dzakadya chikafu chaiva nezvinhu izvi kwemwedzi yakawanda, uye tsvakiridzo haina kuyera mwero wemushonga mumwongo kana chiratidzo chipi nechipi chekukuvadzwa kwemapfupa neoxidation. Mwero unodzvinyirira maosteoclast kana chinhu chacho chikaiswa zvakananga unogona kusambosvika pamasero anotangira maosteoclast mumwongo uri pamwero iwoyo. Tsvakiridzo yakaedza dosi imwe chete pachinhu chimwe nechimwe mumuviri mupenyu, saka mhinduro inobva pakuchinja dosi mumhuka haisati yazivikanwa.

Makemikari ndiyo yechipiri. Reactive oxygen species, mamorekuru eoxygen anokurumidza kuita mamwe mabatirwo emakemikari, haaumbi dziva rimwe chete rakanyatsosanganiswa mukati mesero. Anoshanda munzvimbo duku uye munguva pfupi, uye maitiro eredox mumitochondria, mucytosol, uye pamembrane anoshanda achizvimiririra kusvika pane imwe nhanho. Mitoquinone yakagadzirwa kuti iungane mumitochondria, asi zviratidzo zveoxidation zvinokurudzira kuumbwa kwemaosteoclast zvinogona kubva kune dzimwe nzvimbo. Kuderedza rimwe boka remamorekuru aya hakurevi kuti kuchaita zvakafanana nokuramba uchinyudza sero rose.

Kubatana kwemaitiro ndiyo yechitatu. Mupfupa rinorarama, kuputswa nekuumbwa zvinobatana: maosteoclast nemasero ari pedyo nawo anotumira zviratidzo zvinokwezva masero anovaka pfupa kuti auye panzvimbo ichangobva kuputswa. Kudzvinyirira kuumbwa kwemaosteoclast hakuwedzeri pfupa rakaenzana neinenge yamiswa kuputswa, nokuti kunogonawo kubvisa zviratidzo zvinodana vavaki. Ndiro ine masero anotangira mamwe chete haigoni kuratidza kudyidzana uku. Mapfupa omuviri haagoni kukuvanza.

Mutoro unoiswa pamapfupa ndiyo yechina. Maosteocyte anonzwa kukotamiswa nekumanikidzwa kwemapfupa uye anogadza kuenzana kwekuputswa nekuvakwa patsva kwepfupa rose. Mhuka padzinochembera uye dzofamba zvishoma, chiratidzo chemutoro uyu chinopera simba, uye kurasika kunotevera pasinei nemhedzisiro ine mwero yemushonga parudzi rumwe rwesero. Vanyori pachavo vanotaura kurovedza muviri nemutoro unokurudzira kuvakwa kwemapfupa senzira ingangova nesimba rakakura rokuchinja izvi. Iyi inzira yakapfava yokutaura kuti mapfupa anoteerera mitemo yesimba nemutoro kupfuura makemikari eredox.

Nguva yokutanga ndiyo yechishanu, asi ine muganhu. Mukuedza kweC57BL/6J, kupiwa mushonga kwakatanga pamwedzi 18, apo chikamu chikuru chechimiro chemapfupa chakanga chatorasika. Hapana chinhu chinodzivisa kuputswa kwemapfupa chinogona kuvakazve matanda madiki etrabecular bone akanga atoboorwa uye abviswa pasina kurudziro inoenderana yokuumba pfupa. Asi nguva yokutanga haigoni kutsanangura zvose, nokuti kupiwa zvinhu izvi muInterventions Testing Program kwakatanga mbeva dzichangopinda muzera revakuru uye zvakadaro hakuna kuchinja chinhu. Kutanga kunonoka kunotsanangura chikamu chekumwe kuedza. Hakutsananguri chero chikamu chekumwe kwacho.

Zvinoreva izvi pane zvinotaurwa nezvemethylene blue neosteoporosis

Kumuverengi ari kuongorora methylene blue nokuda kweutano hwemapfupa kana kuchembera kwemapfupa, dudziro inoshanda ipfupi. Humbowo hwakanakisisa huripo hwekuedza kwembeva kwenguva refu hunoti hapana kubatsira mapfupa kwakabva mukupiwa methylene blue kana mitoquinone kwenguva refu, kunyange paiva nechiratidzo chaicho chokudzvinyirira maosteoclast mumasero akakuriswa murabhoritari. Zvinyorwa zveurefu hweupenyu zvinopa methylene blue mhedzisiro ine mwero muchikamu chokupedzisira cheupenyu muhadzi chete, iyo tsvakiridzo iyi inoratidza kuti haina kushanda kuburikidza nemapfupa. Hapana rimwe remapoka maviri ehumbowo aya rinotsigira kushandiswa kwayo muvanhu nokuda kweosteoporosis, uye hapana data remapfupa evanhu rinobatanidzwa zvachose. Mibvunzo yemadosi nekuchengeteka kwechigadzirwa muvanhu iri mukuchengeteka kwemethylene blue nemigumisiro yayo isingadiwi, kwete mumapfupa ebeva iri.

Chidzidzo chakadzama ndechekurongeka kwehumbowo. Zvakawanikwa mumasero zvinotaura zvinogona kuitwa nechinhu chemakemikari parudzi rumwe rwesero mumamiriro ekusangana anodzorwa. Zvakawanikwa mumapfupa zvinotaura zvinoitwa nemwedzi yokusangana nechinhu chinopararira mumuviri wose kunhengo inobatanidza marudzi maviri emasero ichidzorwa nemutoro wemuviri. Pakutanga ndipo panoberekwa pfungwa dzokuedzwa. Pechipiri ndipo pakafa pfungwa iyi, panyaya yekuchembera kwemapfupa nezvinhu zviviri izvi zvinodzivisa oxidation.