Part 2 Kab mob raum ntev thiab Kev Laus Sib Nqus Diminish Pob Txha Khoom Thiab Microarchitecture hauv C57Bl/6 nas

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Pls nyem qhov no mus rau Part 1

Cistanche tuaj yeem pab kho mob raum zoo heev

3. Cov txiaj ntsig

3.1 Kev lees paub ntawm kab mob raum

Ntawm qhov kawg ntawm txoj kev tshawb fawb peb lub hlis ntawm kev phais, nas nrog 5/6 Nx tau nce qib urea hauv cov ntshav thiab txo cov zis urea, zoo ib yam nrog rau lub raum tsis ua haujlwm (Table 1). Serum PTH thiab phosphate tau nce ntxiv raws li cov txiaj ntsig tseem ceeb ntawm CKD. Ntshav calcium tsis cuam tshuam loj heev los ntawm CKD. Rau txhua qhov kev ntsuas ntshav thiab zis, lub hnub nyoog tsis yog qhov tseem ceeb ntawm cov txiaj ntsig.

3.2 Kev laus thiab CKD txo cortical thiab trabecular microarchitecture

Kev lausthiab CKD ob qho tib si cuam tshuam tsis zoo rau cortical geometry thiab trabecular microarchitecture (Tables 2 – 3, Daim duab 1).Kev lausod6 mav. mus 24m. ho nce corticalpob txhaQhov sib txawv ntawm qhov sib txawv (nce polar moment of inertia, PMI), porosity (Ct. Po) thiab cov nqaij mos ntxhia ntom ntom (TMD), thiab txo cov pob txha cortical thickness (Ct. Th), corticalpob txhantim (txo cov pob txha ntim feem (BV / TV),pob txhathaj tsam feem (BA/TA). Kev laus kuj txo tus naj npawb trabecular (Tb. N) thiab tuab (Tb. Th), trabecular pob txha ntim feem (BV / TV), thiab pob txha pob txha pob txha pob txha pob txha (vBMD). Raws li kev laus, CKD kuj muaj qhov cuam tshuam loj heev raupob txhantim ntawm txo BV/TV, Tb. N, BA/TA, Ct. Th, thiab nce Ct.Po. Cov teebmeem no tau ntxiv, xws li cov pob txha loj tshaj plaws tau pom rau cov nas qub nrog CKD. Tsis zoo li kev laus, CKD txo qis BMI thiab TMD. Kev laus thiab CKD tsis muaj kev cuam tshuam loj rau kev ntsuas cortical lossis trabecular microarchitecture.

3.3 Kev laus thiab CKD sib txawv txo qis tag nrho cov pob txha txhua yam thiab cov khoom siv

Ntawm tag nrho cov pob txha, cov khoom siv thiab cov khoom siv kho tshuab tau ploj zuj zus los ntawm kev laus thiab CKD (Table 4, Cov Lus Qhia Ntxiv 1).Kev lausod6 mav. mus 24m. txo qis tag nrho cov khoom siv pob txha tag nrho (piv txwv li, modulus, yield stress, siab tshaj plaws kev nyuaj siab) tab sis tsis cuam tshuam rau toughness. CKD txo qis kev ua haujlwm rau pob txha, tab sis feem ntau lwm yam khoom siv thiab cov khoom siv tshuab tsis raug cuam tshuam los ntawm CKD raws li cov txiaj ntsig tseem ceeb. Toughness, geometry-yooj yim analog ntawm kev ua haujlwm rau pob txha, muaj kev cuam tshuam tseem ceeb ntawm kev laus thiab CKD (p=0.011). Los ntawm kev soj ntsuam tom qab hoc, nws tau pom ntawm 18 mo tias CKD tuaj yeem txo cov tawv nqaij (−47.9 feem pua, p=0.023) (Daim duab 2d).

3.4 Kev laus thiab CKD txo FEA cov qauv nruj ntawm tus tibia proximal

Peb tau siv FEA los ntsuas seb qhov kev laus thiab CKD cuam tshuam li cas rau cov khoom siv kho tshuab los ntawm kev hloov pauv rau cov qauv trabecular thiab cortical. FEA tus qauv nruj ntawm tus tibia proximal txo qis nrog kev laus thiab CKD (Table 4). Tsis muaj kev cuam tshuam tseem ceeb ntawmkev lausthiab CKD. FEA nruj zoo sib raug zoo nrog femoral txhav los ntawm peb-point dabtsi yog khoov (r2=0.67).

3.5 Kev laus txo qis microscale pob txha txhav thaum CKD txo cov pob txha pob txha spatial variation

Yuav ntsuas li caskev lausthiab CKD cuam tshuam cov ntaub so ntswg-scale cov khoom ntawm corticalpob txha, peb ua haujlwm nanoindentation thiab Raman spectroscopy ntawm qhov chaw sib tw los ntsuas microscalepob txhacov ntaub so ntswg modulus thiab muaj pes tsawg leeg (Table 5). Cov pob txha heterogeneity tau soj ntsuam los ntawm kev ntsuam xyuas ntawm qhov sib txawv ntawm qhov sib txawv ntawm cov khoom no. Txhais tau tias txo qis modulus (Er) thiab tus qauv sib txawv ntawmErwere txo qis thiab nce, feem, nrog rau hnub nyoog. CKD txo qis tus qauv sib txawv, tab sis tsis yog qhov txhais tau tias, ntawmEr. Microscale pob txha cov ntaub so ntswg muaj pes tsawg leeg ntsuas los ntawm Raman spectroscopy (ie, txhais tau tias ntxhia: matrix, carbonate: phosphate, crystallinity) tsis tau hloov pauv nrog hnub nyoog lossis CKD. Txawm li cas los xij, tus qauv sib txawv ntawm crystallinity tau txo qis nrog CKD.

3.6 Kev laus thiab CKD sib txawv cuam tshuam rau collagen fibril nanomechanics

Peb tau soj ntsuam seb CKD thiab kev laus puas cuam tshuam rau collagen nanomechanics ntawm me me-lub kaum sab xis x-ray tawg (SAXS) concurrent nrog tensile loading. Raws li kev pom zoo nrog cov txiaj ntsig los ntawm kev khoov, kev ntsuas tensile pom tau tias kev laus txo cov nqaij mos tawm los ntawm kev ntxhov siab thiab max stress. Collagen nanomechanics tau cuam tshuam qhov sib txawv ntawm hnub nyoog thiab CKD (Table 6, Daim duab 2).Kev laustxo cov collagen strain ntsuas ntawm cov ntaub so ntswg ntau tshaj plaws tab sis tsis cuam tshuam rau feem pua ​​collagen hom (collagen strain / tag nrho cov ntaub so ntswg, feem pua ​​ColMax). Los ntawm qhov sib piv, CKD tau nce qhov feem pua ​​​​ColMax.

3.7 Collagen crosslinks tsis txawv nrog kev laus thiab CKD

Peb tau nrhiav kom nkag siab seb qhov hloov pauv ntawm collagen nanomechanics pom hauv CKD tuaj yeem raug ntaus nqi los ntawm kev hloov pauv ntawm cov pob txha pob txha. Peb, yog li ntawd, tus yam ntxwv enzymatic (hydroxyl lysyl pyridinoline, HP, thiab lysyl pyridinoline, LP) thiab tsis-enzymatic cross-linking (pentosidine) nrog high-performance kua chromatography (HPLC). Cov crosslinks HP, LP, thiab pentosidine muaj cov ntsiab lus siab dua nrog cov hnub nyoog nce, tab sis cov kev hloov no tsis tseem ceeb (Table 7). Ib yam li ntawd, muaj qhov sib txawv ntawm LP qis nrog CKD, tab sis qhov txiaj ntsig no tsis tseem ceeb. Peb ntxiv kom suav tag nrho cov fluorescent advanced glycation end-products (AGEs) thiab pom tias tag nrho cov fluorescent AGEs tsis txawv nrog kev laus lossis CKD.

3.8 Cov hnub nyoog ntsig txog osteocyte lacunar geometry hloov pauv tsis tau pom nyob rau hauv cov nas laus nrog CKD

Osteocyte perilacunar/canalicular remodeling (PLR) teb rau cov kev hloov hauv cov ntxhia hauv homeostasis thiab tseem ceeb hauv kev txiav txim siab.pob txhatawg tsis kam. Peb soj ntsuam osteocyte lacunar geometry los txiav txim seb puas yogkev lausnrog CKD hloov PLR (Table 8). Cov teebmeem ntawm kev laus ib leeg (tsis muaj CKD) rau cov Sham nas no tau tshaj tawm yav dhau los (21). Luv luv, rau Sham nas, lacunae tau me me, ntau tus kheej kheej, thiab tsawg dua nrog cov hnub nyoog nce. Thaum kev laus thiab CKD tau txheeb xyuas ua ke rau txoj kev tshawb fawb tam sim no, kev laus txo qis lacunar tus lej ntom ntom, ntim, thiab thaj chaw saum npoo, thiab nce sphericity, oblateness, thiab span theta. Tsis muaj qhov cuam tshuam tseem ceeb ntawm CKD rau ib qho kev ntsuas. Txawm li cas los xij, muaj kev cuam tshuam tseem ceeb ntawm hnub nyoog thiab CKD rau qhov sib txawv. Thaum lub hnub nyoog nce ntxiv nrog rau hnub nyoog rau Sham nas, qhov kev ntsuas no yog qhov zoo tshaj plaws rau cov nas hnub nyoog nruab nrab nrog CKD thiab tom qab ntawd txo qis rau cov nas qub rau tus nqi zoo ib yam li cov nas hluas. Hauv lwm lo lus, lacunae tau ua me me thiab rounder nkaus xwbkev lausSham nas, thiab tsis nyob rau hauv cov nas laus nrog CKD. Cov qauv no kuj tau pom zoo nrog CKD rau lacunar tus lej ceev, ntim, thiab thaj chaw saum npoo, txawm hais tias kev sib cuam tshuam ntawm kev laus thiab CKD tsis tseem ceeb.

Osteocyte lacuna loj tsis tau nce nrog lub hnub nyoog rau nas nrog CKD tab sis hloov zuj zus nrog phosphate dysregulation. Tshwj xeeb, rau cov nas nrog CKD, osteocyte lacunar ntim (Spearman ρ {{{0}}} ntxiv rau 0.584, p=0.017), thaj chaw saum npoo (ρ=ntxiv rau 0.603 p=0.013), thiab sphericity (ρ=- 0.500, p=0.048) muaj feem cuam tshuam nrog cov ntshav phosphate txheeb xyuas ntawm qhov kev kawm kawg. Los ntawm qhov sib txawv, kev ntsuas cuam tshuam nrog lacunae prevalence thiab orientation (piv txwv li, osteocyte tus lej ceev, qhov chaw ze tshaj plaws ntawm pawg, ncua theta) tsis cuam tshuam nrog cov phosphate circulating. Tsis muaj kev ntsuas osteocyte lacunar tau cuam tshuam nrog cov calcium hauv cov ntshav, ntshav urea, lossis cov zis urea. Rau Sham nas, osteocyte lacunar tus lej ceev tau zoo sib raug zoo nrog cov calcium hauv cov ntshav (ρ=ntxiv rau 0.681, p=0.004). Tag nrho lwm yam kev ntsuas osteocyte lacunar tsuas yog tsis muaj zog cuam tshuam nrog cov tshuaj ntshav thiab zis.

Kev sib raug zoo ntawm osteocyte lacuna loj thiab cov ntshav phosphate rau nas nrog CKD tsis ncaj qha los ntawm kev nce PTH. Thaum xav txog Sham thiab CKD nas ua ke, phosphate ho cuam tshuam nrog nce PTH (Spearman ρ {{0}}} ntxiv rau 0.562, p=0.001). Txawm li cas los xij, txawm hais tias phosphate thiab PTH ob leeg tau nce ntxiv raws li cov txiaj ntsig tseem ceeb ntawm CKD, cov kev ntsuas no tsis cuam tshuam nrog ib leeg rau CKD nas (p > 0.05). Tsis muaj kev ntsuas ntawm osteocyte lacunar geometry ho cuam tshuam nrog PTH rau Sham lossis CKD nas.

3.9 Regression tsom xam qhia tias hloov collagen nanomechanics cuam tshuam toughness

Peb nrhiav kev txheeb xyuas yuav ua li cas kev hloov pauv rau tag nrho cov pob txha toughness los ntawm dabtsi yog khoov tau cuam tshuam nrog kev hloov pauv hauv nano-rau microscale ntsuas ntawmpob txhazoo rau Sham thiab CKD nas. Peb tau ua ib qho kev rov qab ntawm pob txha pob txha tag nrho raws li cov pob txha zoo ntsuas ntawm qhov ntev me me rau Sham thiab CKD nas siv hnub nyoog raws li covariate. Rau Sham nas, tsis muaj kev ntsuas pob txha zoo yog qhov tseem ceeb piav qhia txawv rau qhov tawv. Rau CKD, tib qhov kev kwv yees tseem ceeb ntawm qhov tawv (T) yog feem pua ​​ColMax (ln(T)=2.437 – 0.00371* feem pua ​​ColMax; r2=49 .4 feem pua, p <0.05). lub="" zog="" ntawm="" regression="" tsis="" tau="" txhim="" kho="" los="" ntawm="" kev="" kho="" rau="" lub="" hnub="">

3.10 Kev hloov pauv pob txha zoo tsis tau piav qhia los ntawm kev hloov pauv hauv PTH

Peb tau soj ntsuam Spearman kev sib raug zoo ntawm cov pob txha zoo ntsuas thiab PTH kom nkag siab yog tias cov nas uas muaj PTH siab dua tuajpob txhazoo. Txawm hais tias PTH tau siab dua nrog 5/6 Nx, tsis muaj kev sib raug zoo ntawm PTH thiab microscale pob txha zoo.

4. Kev sib tham

Lub hom phiaj ntawm txoj kev tshawb no yog los tshawb xyuas seb 5/6 Nx - ntxias CKD thiabkev laustxhua diminishes pob txha zoo, nrog raupob txhamicroarchitecture nrog rau cov pob txha cov ntaub so ntswg cov khoom. CKD txo cov pob txha zoo, suav nrog microarchitecture thiab cov khoom siv, los ntawm micrometer-ntev nplai mus rau tag nrho cov pob txha nplai. Hauv peb txoj kev tshawb fawb, cov pob txha tsis zoo tau pom nyob hauv ntau qhov kev hloov pauv thiab qhov ntev. Cov nyhuv ntawm CKD yog txo qis cortical thiab trabecular microarchitecture, hloov spatial variation nyob rau hauv microscale khoom zog, thiab kuj hloov collagen nanomechanics. Tsis tas li ntawd, CKD thiab kev laus muaj ib qho

kev sib tham sib cuam tshuam rau qhov tawv nqaij uas zoo tshaj plaws rau cov nas hnub nyoog nruab nrab. Peb cov txiaj ntsig tau qhia tias ntau lub ntsiab lus tseem ceeb ntawm cov pob txha tsis zoo hauv CKD. Cov kev soj ntsuam no txhawb nqa lub cev loj hlob ntawm cov pov thawj los ntawm cov nas thiab cov kev tshawb fawb soj ntsuam tias cov pob txha zoo txo ​​qis hauv CKD thiab yuav ua rau poob ntawm kev puas tsuaj.

Qhov poob ntawmpob txhamicroarchitecture nrog CKD tshwm sim ntxiv rau cov teebmeem deleterious ntawmkev lausthiab pab kom poob tag nrho-pob txhazog. Hauv qhov kev tshawb fawb no, peb pom tiaskev lausthiab CKD ob qho tib si txo qis cortical thiab trabecular microarchitecture. Kev laus thiab CKD txhua qhov ua rau nyias nyias, cov pob txha cortical ntau dua, thiab tsawg dua thiab nyias trabeculae. Qhov tsuas yog qhov tshwj xeeb yog pob txha pob txha raug soj ntsuam los ntawm microCT (piv txwv li, TMD), uas tau nce nrog hnub nyoog thiab tau ploj mus hauv CKD. Rau txhua qhov kev ntsuas cortical thiab trabecular, qhov phem tshaj plaws ntawm cov pob txha microarchitecture tau pom meej hauv cov nas qub nrog CKD. Qhov poob ntawmpob txhamicroarchitecture cuam tshuam tag nrho cov pob txha pob txha kev ncaj ncees. Los ntawm FEA, nws tau pom tias kev laus txo cov pob txha microarchitecture ntawm tus tibia proximal thaum CKD txo cov txheej txheem nruj.

Rau kev ntsuas ntsig txogpob txhacov khoom zoo, hnub nyoog thiab CKD muaj qhov sib txawv (Daim duab 2). Nrog rau lub hnub nyoog nce, tag nrho cov pob txha modulus thiab qhov siab tshaj plaws kev ntxhov siab tau txo qis, zoo li micrometer-scale cov ntaub so ntswg modulus. Tawm los thiab qhov siab tshaj plaws kev ntxhov siab los ntawm kev sim tensile ntawm lub ulna-radius kuj txo nrog hnub nyoog. Ntxiv mus, raws li tib neeg cov qauv kawm nrog SAXS,kev laustau txuam nrog ntxiv collagen strain ntawm qhov siab tshaj plaws, implying ib tug stiffening ntawm collagen fibers (26). CKD tsis cuam tshuam rau tag nrho cov pob txha modulus lossis lub zog, tab sis es tsis txhob txo qis kev ua haujlwm rau pob txha, thiab hloov cov ntaub so ntswg-scale cov ntaub ntawv spatial variation. Tsis tas li ntawd, CKD tuaj yeem txo cov tawv nqaij hauv nruab nrab cov nas, zoo li nrog tus kab mob no lub nra ntawm tensile strain tau hloov mus rau collagen fibers. Kev nce feem pua ​​​​ntawm collagen ntawm qhov siab tshaj plaws tsuas yog qhov kev piav qhia tseem ceeb rau kev txo qis hauv CKD, qhia tias qhov poob ntawm pob txha tag nrho yuav yog qhov tsawg kawg yog ib feem piav qhia los ntawm kev hloov kho collagen.

Lub hauv paus chiv keeb ntawm hloov collagen nanoscale mechanical cwj pwm tsis paub meej. Muaj qhov sib txawv ntawm cov pob txha pob txha sib txuas nrog CKD. Txawm li cas los xij, HP thiab LP ntsuas los ntawm humerus tsis cuam tshuam nrog cov khoom siv collagen los ntawm SAXS ntsuas ntawm ulna / radius complex, tej zaum vim muaj qhov sib txawv ntawm kev tshuaj xyuas. Qhov kev hloov pauv no kuj tseem tuaj yeem tshwm sim los ntawm kev hloov cov ntxhia hauv cov ntsiab lus lossis kev faib tawm, lossis kev hloov pauv rau kev khi ntawm collagen thiab ntxhia. Kev nce feem pua ​​​​ColMax yuav tsis yog lub luag haujlwm ncaj qha rau qhov poob ntawm qhov hnyav hauv CKD tab sis tuaj yeem yog cov tsos mob cuam tshuam txog kev hloov pauv hloov pauv thiab qhov tsis zoo hauv lub koom haum pob zeb. Piv txwv li, hloov pauv mineralization tuaj yeem ua rau collagen ntau lub xov tooj ntawm tes, lossis tuaj yeem cuam tshuam tsawg zog los ntawm microcracking. Cov kev hloov pauv no tuaj yeem ua rau pom qhov poob ntawm qhov tawv nqaij nrog CKD nrog rau lub nra hnyav ntxiv ntawm collagen fibers. Hauv kev tshawb fawb yav tom ntej, nws yuav yog ib qho tseem ceeb kom paub tias yog vim li cas CKD hloov strain rau collagen fibers, tab sis ntawm no peb nco ntsoov tias qhov kev hloov ntawm collagen tus cwj pwm zoo li ua lub luag haujlwm tseem ceeb hauv CKD txo qis cov khoom siv pob txha tag nrho.

Raws li kev hloov pauv rau cov pob txha cov khoom siv tau tshwm sim nrog CKD thiab osteocyte paub los hloov cov ntaub so ntswg-scalepob txhazoo los ntawm perilacunar / canalicular remodeling (PLR), peb kuj tsom kom nkag siab seb 3D osteocyte lacunar morphologies tau hloov kho hauv CKD (15, 16). Thaum osteocyte lacunae ua me me, sparser, thiab tsawg dua nrog lub hnub nyoog nce rau Sham nas, lacunae tseem muaj ntau thiab loj rau cov nas qub nrog CKD.

Hloov chaw, rau cov nas nrog CKD, ntshav phosphate tau zoo thiab muaj kev cuam tshuam zoo nrog osteocyte lacuna loj. Txawm hais tias ob qho tib si phosphate thiab PTH tau nce siab

Nrog CKD, nas nrog PTH siab dua tsis muaj phosphate ntau dua. Cov txiaj ntsig no tsis tas yuav muaj kev sib cav. Serum phosphate yog cov txiaj ntsig ntawm phosphate ntxiv los ntawm txoj hnyuv nqus thiabpob txharesorption tsawg phosphate tshem tawm los ntawm lub raum excretion thiab pob txha tsim. Yog li, txawm hais tias peb cov nas CKD feem ntau tau nce siab PTH, cov uas muaj phosphate ntau dua tuaj yeem ua rau tag nrho lwm cov txheej txheem them nyiaj.

Osteocytes qhia ntau dua FGF23 nyob rau hauv cov ntsiab lus ntawm impaired mineralization (piv txwv li, DMP1 knockout, x-linked hypophosphatemia) (20,48,49) thiab nyob rau hauv mob raum kab mob (14,48,50). Cov pov thawj tsis ntev los no qhia tias ntxiv rau lub luag haujlwm endocrine no, osteocyte tuaj yeem koom ncaj qha rau hauv phosphate mineral homeostasis viaPLR (20). Osteocyte lacunae ntim tau pom tias nce nrog x-txuas hypophosphatemia. Kev kho mob nrog FGF23 los yog 1,25 dihydroxyvitamin D thaiv cov tshuaj tiv thaiv kab mob rov qab osteocyte lacunar ntim kom muaj nuj nqis ze dua rau cov tsiaj qus sib piv (20). Nyob rau hauv CKD, mineral dysregulation yog thawj zaug spurred los ntawm qhov txo phosphate pom ntawm lub raum mob. Ncepob txhaturnover yog cov lus teb tsis zoo uas qhia tau tias cov txheej txheem them nyiaj rau kev tswj hwm phosphate tau dhau los (6,7). Hauv qhov no, kev sib raug zoo ntawm qhov siab phosphate thiab nce osteocyte lacunar ntim qhia tau hais tias PLR tuaj yeem yog ib qho kev cai ntxiv ntawm cov ntxhia hauv homeostasis. Kev tshawb fawb ntxiv yuav tsum tau tshawb xyuas seb osteocyte lacunar geometries thiab PLR cuam tshuam li cas rau cov pob txha hloov pauv, pob txha cov ntaub so ntswg zoo, thiab pob txha tiv thaiv hauv CKD.

Peb qhov kev tshawb pom qhia tias cov txheej txheem cuam tshuampob txhacov khoom sib txawv hauvkev lausvs CKD. Hauv cov neeg laus thiab cov nas,pob txhaturnover (piv txwv li, osteoclastic resorption thiab osteoblastic tsim) qeeb, thiab cov ntaub so ntswg kom loj tuaj. Hauv txoj kev tshawb no, 5/6 Nx tsim cov pob txha tsis zoo los ntawm kev laus, xws li cov pob txha qis los ntawm microCT, kev hloov pauv ntawm cov ntaub so ntswg-scale cov khoom, thiab kev koom tes ntau dua ntawm collagen hauv tensile loading. Txawm hais tias PTH siab dua nrog CKD, cov nas uas muaj PTH siab dua tsis muaj cov pob txha qis dua. Ntau qhov laj thawj tuaj yeem piav qhia qhov kev tshawb pom no. Ua ntej, cov nas hauv peb txoj kev tshawb fawb tau qis dua PTH ntau dua li hauv cov kev tshawb fawb nrog CKD hnyav thiab concomitant secondary hyperparathyroidism (9, 12). Nws yog qhov ua tau tias kev hloov pauv ntawm cov pob txha hloov pauv tau qis qis hauv peb txoj kev tshawb fawb. Txawm li cas los xij, peb tsis tau txheeb xyuas cov pob txha ncaj qha, yog li qhov ua tau yog kwv yees. Thib ob, CKD, tsis hais txog qhov hloov pauv hloov pauv, tau sim ua haujlwm nrog cov pob txha hloov pauv zoo. Iwasaki thiab cov neeg ua haujlwm tau tshaj tawm tias qhov kev hloov pauv siab CKD los ntawm 5/6 Nx nrog rau kev hloov pauv qis CKD los ntawm 5/6 Nx thiab thyroparathyroidectomy ob qho tib si ua rau cov pob txha hloov pauv zoo sib xws, thiab ua rau cov kev hloov pauv no rau uremia (11). Nws yog qhov ua tau tias cov pob txha tsis zoo tsis yog tsuas yog nyob rau theem nrab hyperphosphatemia tab sis kuj cuam tshuam los ntawm kev hloov pauv me me hauv cov pob txha hloov pauv thiab sib sau ntawm uremic toxins.

Peb cia siab tias ob pebpob txhakev ntsuas zoo, suav nrog tag nrhopob txhatoughness, pentosidine, ntxhia: matrix, thiab carbonate: phosphate yuav hloov ntawm 6 mus rau 24 lub hlis (25,26,30,51,52). Txawm hais tias txhua qhov kev ntsuas no tau hloov pauv raws li qhov xav tau nrog lub hnub nyoog nce, qhov cuam tshuam ntawm lub hnub nyoog tsis yog qhov tseem ceeb. Tom qab hoc zog tsom xam siv G*Power (53) qhia tias toughness, pentosidine, thiab ntxhia: matrix tau underpowered los xyuas cov nyhuv ntawmkev laus, thaum carbonate: phosphate yuav tsis cuam tshuam los ntawm hnub nyoog hauv txoj kev tshawb no. Tsis tas li ntawd, collagen crosslink LP tau ua rau tsis muaj zog rau kev tshawb pom ntawm cov nyhuv ntawm CKD (Table 2). Muaj ntau qhov ua tau vim li cas qee qhov kev ntsuas ntawm cov pob txha zoo thaum kawg tsis muaj zog hauv txoj kev tshawb no. Ua ntej, peb tau siv cov cuab yeej Raman-nanoindentation kev cai nrog qhov tshwj xeeb kom zoo dua ntawm kev ntsuas hauv zos. Kev siv lub teeb liab qis dua ntawm qhov ntsuas kev cai no dua li cov twj paj nruag Raman ib leeg, thiab yog li nws muaj peev xwm hais tias peb lub teeb liab: suab nrov piv tsis txaus los txiav txim siab txog kev hloov pauv hnub nyoog. Toughness (xam los ntawm kev ua hauj lwm mus rau tawg) yog ib qho kev ntsuas uas muaj kev hloov pauv siab (54), thiab qhov sib txawv ntawm cov khoom siv kho tshuab yog nce ntxiv rau cov nas geriatric (25). Kev hloov pauv ntau dua hauv pentosidine kuj tau pom nrog lub hnub nyoog nce ntxiv hauv tib neeg thiab nas kev tshawb fawb (52,55,56). Yog li nws zoo li qhov sib txawv ntawm cov kev ntsuas no tsis pom qhov sib txawv ntawm cov neeg soj ntsuam.

Ntau qhov kev txwv cuam tshuam rau qhov tshwm sim ntawm qhov kev tshawb fawb no. Dynamic quantitative histomorphometry tsis tau ua, tab sis cov kev tshawb fawb yav tom ntej yuav ua rau kev ntsuam xyuas ntawm osteoblast, osteoclast, thiab osteocyte kev ua ub no nrog raupob txhakev hloov pauv. Thaum peb txheeb xyuas ntau yam pob txha tsis zoo uas tshwm sim nrog CKD thiab tshem tawm tag nrho cov pob txha toughness, yuav tsum ua hauj lwm ntxiv kom paub meej tias lub hauv paus pib ntawm cov kev puas tsuaj no, nrog rau lub luag haujlwm ntawm osteocyte hauv lawv qhov tshwm sim. Kev tshuaj xyuas cov noob thiab cov protein qhia yuav muaj txiaj ntsig hauv kev txheeb xyuas lub hauv paus chiv keeb ntawm kev puas tsuaj collagen nanomechanics, vim qhov kev puas tsuaj no tsis cuam tshuam los ntawm kev hloov pauv hauv collagen crosslinks. Tsis tas li ntawd, peb txoj kev txhais ntawm yuav ua li cas cov osteocyte tuaj yeem koom nrog hauv kev tswj hwm cov ntxhia hauv homeostasis thiab tswj cov pob txha zoo hauv CKD yuav tsum muaj lub ntiaj teb ntxiv (piv txwv li, gene qhia) thiab kev ntsuas hauv zos (piv txwv li, kev soj ntsuam histological ntawm pob txha resorption thiab tsim).

Hauv cov ntsiab lus, peb pom tias CKD txo qis pob txha zoo ntxiv rau cov teebmeem ntawmkev lausib leeg. CKD thiab aging zoo ib yam li txo cortical thiab trabecularpob txhamicroarchitecture xws li tias qhov kev poob siab tshaj plaws ntawm microarchitecture tau pom nyob rau hauv cov nas qub nrogmob raum. CKD kuj tseem txo qis cov khoom siv pob txha, ua rau cov pob txha nrog qis dua cov ntaub so ntswg kom loj hlob nrog hloov collagen nanomechanics. Cov kev txo qis hauvpob txhazoo, suav nrog microarchitecture thiab cov khoom siv pob txha, muab kev nkag siab txog yuav ua li cas tawg tsis kam poob hauv CKD. Tsis tas li ntawd, kev sib xyaw ua ke ntawmkev lausthiab CKD ntawm cov pob txha zoo pab piav qhia vim li cas cov neeg laus nrog CKD muaj kev pheej hmoo siab tshaj plaws ntawm pob txha.

Khoom siv ntxiv

Xa mus rau Web version ntawm PubMed Central rau cov khoom siv ntxiv.

Kev lees paub:

Peb xav ua tsaug rau William Schroeder rau lawv txoj kev saib xyuas zoo heev ntawm kev kawm tsiaj, thiab William Schroeder thiab Ryan Clark rau kev tshuaj ntsuam xyuas tshuaj lom neeg. Kev them nyiaj yug tau muab rau CMH txog NIHT32 AG000279. Cov nyiaj pab rau txoj haujlwm no kuj tau muab rau KBK thiab VLF los ntawm NIH/NCATS Colorado CTSA Grant Number UL1 TR001082, Co-Pilot Team Science Award. Cov nyiaj pab rau TA yog muab los ntawm R01 DE019284. Kev tsom xam ua ke siv nanoindentation thiab Raman spectroscopy tau ua tiav los ntawm kev siv cov cuab yeej kev cai los ntawm NSF Major Research Instrumentation Award #1338154. X-ray tawg ntawm Beamline 7.3.3 ntawm Advanced Light Source tau txais kev txhawb nqa los ntawm US Department of Energy Office Basic Energy Sciences raws li Daim Ntawv Cog Lus No. DE-AC02– 05CH11231. Peb kuj ua tsaug rau pawg AZ Weber ntawm LBL rau kev muab lawv cov theem tensile, uas tau txais kev txhawb nqa los ntawm DOE EERE Fuel-Cell Performance and Durability Consortium (FC-PAD).

Cov ntaub ntawv

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