Ntu 3: Acteoside Counteracts Interleukin-1 -Induced Catabolic Processes Los ntawm Kev Hloov Kho Ntawm Mitogen-Activated Protein Kinases Thiab NFκB Cellular Signaling Pathway

Acteoside Counteracts Interleukin-1 -Induced Catabolic Processes los ntawm Modulation ntawm Mitogen-Activated Protein Kinases thiab NFκB Cellular Signaling Pathway

Hyang I Lim, 1 Do Kyung Kim, 1 Tae-Hyeon Kim, 1 Kyeong-Rok Kang, 1 Jeong-Yeon Seo, 1,2 Seung Sik Cho, 3 Younghee Yun, 4,5 Ye-yong Choi, 4,5 Jungtae Leem ,4,5 Hyoun-Woo Kim ,6 Geon-Ung Jo ,6

Chan-Jin Oh, 6 Deuk-Sil Oh, 6 Hong-Sung Chun, 2 thiab Jae-Sung Kim 1.

Hu rau:joanna.jia@wecistanche.com/ WhatsApp: 008618081934791

1Institute of Dental Science, Chosun University, Gwangju 61452, koom pheej ntawm Kauslim Teb

2 Department of Biomedical Science, Chosun University, Gwangju 61452, koom pheej ntawm Kauslim Teb

3 Department of Biomedicine, Health & Life Convergence Sciences, BK21 Plaub, College of Pharmacy, Mokpo National University,

Jeonnam 58554, koom pheej ntawm Kaus Lim Kauslim

4Chung-Yeon Medical Institute, Gwangju 61949, koom pheej ntawm Kaus Lim Kauslim

5Research and Development Institute, CY Pharma Co., Seoul 06224, Republic of Kauslim

6Jeollanamdo Forest Resources Institute, Naju, Jeollanamdo, 58213, Republic of Kauslim

Cov ntawv xov xwm yuav tsum tau hais rau Jae-Sung Kim; js{1}kim@chosun.ac.kr

Tau txais 2 Lub Xya Hli 2020; Hloov kho 15 Lub Ob Hlis 2021; Tau txais 6 Lub Peb Hlis 2021; Luam tawm Lub Peb Hlis 25, 2021

Academic Editor: Joël R. Drevet

Copyright © 2021 HyangI Lim et al. Qhov no yog ib tsab xov xwm qhib nkag tau muab faib raws li CreativeCommonsAttributionLicense,

uas tso cai rau kev siv tsis txwv, kev faib tawm, thiab luam tawm hauv ib qho nruab nrab, yog tias cov haujlwm qub raug suav hais tias yog.

Osteoarthritis (OA) yog cov kab mob uas feem ntau degenerative sib koom ua ke nrog mob pob qij txha uas tshwm sim los ntawm kev loj hlob ntawm cov pob txha mos ntawm cov pob qij txha ntawm cov pob qij txha.Acteoside, caffeoylphenylethanoid glycoside, muaj ntau yam kev ua ub no xws li tshuaj tua kab mob, tshuaj tiv thaiv kab mob, tshuaj tiv thaiv kab mob, tshuaj tiv thaiv oxidative, cytoprotective, thiab neuroprotective effective. Ntxiv mus, qhov ncauj tswj hwm ntawmacteosidentawm qhov ntau npaum li cas tsis ua rau genotoxicity. Yog li ntawd, lub hom phiaj ntawm txoj kev tshawb fawb tam sim no yog txhawm rau txheeb xyuas cov txiaj ntsig ntawm anticatabolicacteosidetiv thaiv osteoarthritis thiab nws cov anticatabolic signaling txoj kev.Acteosidetsis txo qis qhov ua tau zoo ntawm nas fibroblast L929 hlwb siv los ua cov hlwb qub thiab thawj cov nas chondrocytes.Acteosidecounteracted IL-1 -induced proteoglycan poob nyob rau hauv chondrocytes thiab articular pob txha mos los ntawm suppressing qhia thiab ua kom cov pob txha-degrading enzymes xws li matrix metalloproteinase- (MMP-) 13, MMP-1, thiab MMP{{ 6}} ib. Tsis tas li ntawd, acteoside inhibited qhov kev qhia ntawm inflammatory mediators xws li inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, thiab prostaglandin E2 nyob rau hauv thawj nas chondrocytes kho nrog IL-1 . Tom qab ntawd, kev qhia ntawm proinflammatory cytokines tau txo qis los ntawm acteoside hauv thawj nas chondrocytes kho nrog IL-1 . Ntxiv mus, acteoside suppressed tsis yog tsuas yog cov phosphorylation ntawm mitogen-activated protein kinases nyob rau hauv thawj nas chondrocytes kho nrog IL-1 tab sis kuj translocation ntawm NFκB los ntawm lub cytosol mus rau lub nucleus los ntawm suppression ntawm nws phosphorylation. Kev tswj qhov ncauj ntawm 5 thiab 10mg / kgacteosideattenuated lub zuj zus degeneration ntawm articular pob txha mos nyob rau hauv lub osteoarthritic nas qauv generated los ntawm destabilization ntawm medial meniscus. Peb qhov kev tshawb pom qhia tias acteoside yog ib qho kev cog lus muaj peev xwm tiv thaiv kab mob los yog ntxiv kom txo qis lossis tiv thaiv kev loj hlob ntawm cov pob txha mos.

Pls nyem qhov no mus rau Ntu 2

acteosidehauv cistanche tautxhawb kev tiv thaiv kab mob

Cov pob txha mos-degrading enzymes suav nrog MMP-1, MMP-3, MMP-13, ADMITS-4, thiab ADAMTS-5 hauv cov kua dej synovial ntawm cov neeg mob OA yog cov enzymes tseem ceeb lub luag hauj lwm rau kev loj hlob degeneration ntawm pob txha pob txha los ntawm degradation ntawm collagen thiab ECM tivthaiv [26, 27]. Yog li ntawd, qhov inhibition ntawm MMP kev qhia thiab kev ua kom zoo li yog ib qho kev zoo nkauj kho kom zoo nkauj los tiv thaiv thiab txo qis kev loj hlob ntawm cov pob txha mos rau kev tswj xyuas qhov kev ua haujlwm ntawm cov pob qij txha synovial [26]. Hauv txoj kev tshawb fawb tam sim no, acteoside tau cuam tshuam qhov kev qhia thiab ua kom cov pob txha mos-degrading enzymes hauv thawj nas chondrocytes kho nrog.proinflammatorycytokine IL-1 raws li qhia hauv daim duab 4. Cov ntaub ntawv no qhia tau hais tias acteoside tuaj yeem txo qis kev loj hlob ntawm cov pob txha mos los ntawm kev tawm tsam cov lus qhia thiab ua kom cov pob txha mos hauv cov pob txha synovial nrog cov kab mob catabolic.

Covua npawsCov neeg nruab nrab xws li iNOS, NO, COX-2, thiab PGE2 yog qhov tseem ceeb rau OA pathogenesis [28]. Tshwj xeeb,proinflammatorycytokines xws li IL-1 thiab TNF upregulate zus tau tej cov NO thiab PGE2 los ntawm kev nce ntawm iNOS thiab COX2, raws li, nyob rau hauv lub synovial sib koom nrog OA [29, 30]. Upregulated NO inhibits cov synthesis ntawm ECM Cheebtsam xws li hom II collagen thiab proteoglycan. Tsis tas li ntawd, nce PGE2 inhibits kev loj hlob ntawm chondrocytes thiab txo cov synthesis ntawm ECM [28]. Li no, suppression ntawmua npawsCov neeg kho kom haum xeeb tuaj yeem ua rau txo qis qhov kev loj hlob ntawm cov pob txha pob txha pob txha los ntawm kev cuam tshuam ntawm ECM txo qis hauv synovial sib koom nrog OA. Hauv kev tshawb fawb tam sim no, acteoside tau cuam tshuam qhov kev tswj hwm ntawmua npawsCov neeg kho kom haum xeeb raws li pom hauv daim duab 5. Cov ntaub ntawv no qhia tsis tu ncua tias acteoside tuaj yeem txo qis kev loj hlob ntawm cov pob txha mos los ntawm kev tawm tsam ntawm cov kab mob sib kis hauv cov synovial sib koom nrog OA.

acteosidehauvcistanchetuaj yeem tiv thaivmob

Ntxiv mus, qhov overexpression ntawm proinflammatory cytokines los ntawm inflamed synovium thiab chondrocytes yog ib tug loj txaus ntshai pathogenic yam nyob rau hauv OA pathogenesis. Tshwj xeeb tshaj yog, qhov kev qhia ntawm proinflammatory cytokine yog xav tias yog tsim los ntawm cov synovial membrane ntawm theem ntawm OA pib. Raws li txoj cai, cov cytokines txhawb nqa kev ua haujlwm chondrocytes los qhia lawv tus kheej qhia thiab ua ke cov pob txha mos-degrading enzymes, chemokines, thiab inflammatory mediators [31]. Yog li ntawd, kev tawm tsam ntawm proinflammatory cytokines tuaj yeem tiv thaiv OA thiab tuaj yeem txo qis kev loj hlob ntawm cov pob txha mos los ntawm kev cuam tshuam ntawm lwm cov cytokines proinflammatory cytokines, inflammatory mediators, thiab pob txha mos-degrading enzymes. Nyob rau hauv txoj kev tshawb no, acteoside suppressed zus tau tej cov proinflammatory cytokines xws li CINC-2, CINC-3, CNTF, fractalkine, IL-1, IL-1, leptin, MCP{ {7}}, MIP-3 , thiab -NGF hauv thawj nas chondrocytes kho nrog IL-1 piv nrog IL-1 ib leeg, raws li pom hauv daim duab 6.

Gouze et al. qhia tias CINC-2 tau nce ntxiv hauv chondrocytes kho nrog IL-1 zoo ib yam li peb txoj kev tshawb fawb [32]. Txawm li cas los xij, ib txoj kev tshawb fawb tsis ntev los no tau pom tias kev ua haujlwm ntawm tus txha caj qaum ntawm cov kev mob tshwm sim tau raug hloov pauv zoo thaum OA pathogenesis [33]. Hais txog kev mob pob qij txha, CINC-2 thiab CINC-3 tau ua kom muaj txiaj ntsig zoo nyob rau hauv tus txha caj qaum dorsal horn ntawm OA tsiaj uas tsim los ntawm kev txhaj tshuaj intra-articular ntawm monosodium iodoacetate rau hauv lub hauv caug pob qij txha [34, 35]. Txawm hais tias lub luag haujlwm pathophysiological ntawm CINC-2 thiab CINC-3 hauv OA pathogenesis tseem tsis tau paub ntau, cov kev tshawb fawb no qhia tau hais tias qhov kev qhia ntawm CINC-2 thiab CINC-3 nyob rau hauv tus txha caj qaum dorsal horn nyob rau hauv OA tej yam kev mob tej zaum yuav ze ze nrog kev loj hlob ntawm kev sib koom mob thaum lub sij hawm OA pathogenesis.

CNTF, uas yog pluripotent neurotropic yam tseem ceeb thiab muaj feem xyuam nrog tsev neeg cytokine uas suav nrog IL-6, IL-11, leukemia inhibitory tsev neeg, thiab oncostatin, khi thiab teeb liab los tswj cov pob txha homeostasis los ntawm gp130 coreceptor. subunit [36]. Txawm hais tias kev ua haujlwm lom neeg ntawm CNTF tseem tsis paub ntau hauv OA, cov kev tshawb fawb tsis ntev los no tau pom tias CNTF-gp130 teeb liab tuaj yeem cuam tshuam nrog kev kho pob txha pathologic pom tseeb hauv rheumatoid mob caj dab (RA), kab mob periodontal, spondyloarthropathies, thiab OA los ntawm kev tswj hwm qhov sib txawv thiab. Kev ua haujlwm ntawm osteoblast, osteoclast, thiab chondrocytes [36]. Tsis tas li ntawd, ib txoj kev tshawb fawb tsis ntev los no tau pom tias -NGF, qhov cuam tshuam rau neurotrophic cuam tshuam nrog

Kev tswj hwm lub cev ntawm cov hlwb neuronal tau tswj hwm hauv cov ntshav thiab cov kua dej synovial hauv cov neeg mob OA [37]. Txawm li cas los xij, ntau qhov kev tshawb fawb tau tshaj tawm tias qhov thaiv ntawm NGF txo OA mob [38–40]. Yog li ntawd, neurotropic yam xws li CNTF thiab NGF tsis tsuas yog suav hais tias yog cov kab mob muaj feem cuam tshuam ntawm OA kev loj hlob, tab sis kuj tseem muab cov kev sib txuas ntawm cov paj hlwb ntawm cov pob txha mos ntawm cov pob txha mos thiab kev loj hlob ntawm OA mob. Tsis tas li ntawd, nws tau raug suav hais tias yog kev kho mob lub hom phiaj molecule kom txo qis OA mob ntev.

Fractalkine tseem hu ua chemokine CX3CL1 yog exuberantly qhia nyob rau hauv ob leeg neeg laus thiab nas articular chondrocytes kho nrog IL-1 [41, 42]. Cov kev tshawb fawb tsis ntev los no tau tshaj tawm tias fractalkine txhawb kev qhia ntawm MMP- 3 los ntawm CX3CR1, c-Raf, MEK, ERK, thiab NFκB cellular signaling pathways hauv cov ntaub so ntswg synovial tau los ntawm cov neeg mob OA [43]. Tsis tas li ntawd, genomic-wide DNA methylation tsom hauv OA chondrocytes tau qhia tias cov noob fractalkine tsis yog hypomethylated nkaus xwb tab sis kuj tseem cuam tshuam nrog nws cov mRNA qhia [44]. MCP-1, ib tug tswv cuab ntawm tsev neeg chemokine los ntxias cov kab mob, ua rau chemotaxis, thiab transendothelial migration ntawm monocyte mus rau qhov txhab mob. Tsis ntev los no, Xu li al., tau tshaj tawm tias MCP-1 thiab chemokine (CC motif) receptor 2 axis koom nrog kev degradation ntawm pob txha mos los ntawm kev qhia ntawm MMP-13 thiab nce ntawm OA chondrocyte apoptosis. [45]. Tsis tas li ntawd, MIP-3 kuj hu ua chemokine CCL20 tau nthuav tawm ntau nyob rau hauv cov pob txha pob txha ntawm cov neeg mob uas muaj OA thiab ua rau cov pob txha pob txha loj zuj zus los ntawm kev qhia ntawm pob txha mos-degrading enzymes xws li MMP-1 thiab MMP -3, tus neeg nruab nrab ntawm tus kab mob xws li PGE2, thiab proinammatory cytokine IL-6 [46]. Yog li ntawd, cov tshuaj chemokines xws li fractalkine, MCP-1, thiab MIP{27}} kuj tau raug suav hais tias yog ib qho kev pheej hmoo ntawm pathophysiological los pib qhov kev loj hlob ntawm OA.

Leptin yog peptide cov tshuaj hormones ntawm adipokines, uas yog cytokines secreted los ntawm cov ntaub so ntswg adipose [47]. Cov kev tshawb fawb tsis ntev los no tau tshaj tawm tias qib ntawm leptin tsis yog tsuas yog nce siab hauv tib neeg lub cev nrog kev rog, tab sis kuj nce ntxiv hauv cov ntshav thiab cov kua dej synovial sau los ntawm cov neeg mob OA uas cuam tshuam nrog OA hnyav [48]. Yog li, cov kev tshawb fawb tsis ntev los no tau qhia tias cov lus qhia ntawm leptin thiab nws cov receptor tau raug suav tias yog qhov muaj feem cuam tshuam nrog kev loj hlob ntawm OA [49–51]. [52] IL-1 tsev neeg, suav nrog IL-1 thiab IL-1, yog suav tias yog qhov tseem ceeb tshaj plaws cytokine cuam tshuam nrog pathogenesis ntawm OA uas ua rau cov txheej txheem catabolic ua ke nrog lwm yam catabolic xws li raws li kev laus, rog rog, thiab raug mob sib koom tes [53]. Feem ntau, theem ntawm IL-1 tsev neeg nyob rau hauv lub synovial uid, synovial membrane, articular pob txha, thiab cov pob txha subchondral yog siab nyob rau hauv lub synovial sib koom ntawm cov neeg mob OA [54]. Tom qab IL -1 tsev neeg khi rau lawv cov receptors, nws tshwm sim qhov kev loj hlob ntawm cov pob txha mos los ntawm kev qhia ntawm lwm yam cytokines, chemokines, adhesion molecules, inflammatory mediators, thiab pob txha-degrading enzymes los ntawm phosphorylation ntawm cellular transcription. xws li NFκB thiab MAPKs [54]. Raws li pom nyob rau hauv daim duab 7, acteoside tsis tsuas yog txo cov phosphorylation ntawm ERK1/2, p38, thiab JNK tab sis kuj inhibited phosphorylation ntawm NFκB hauv thawj nas chondrocytes kho nrog IL-1 . Ntxiv mus, daim duab 8 qhia tau hais tias acteoside inhibited kev hloov ntawm NFκB los ntawm cytosol mus rau lub nucleus hauv thawj nas chondrocytes kho nrog IL-1 . Yog li, peb cov txiaj ntsig tsis tu ncua qhia tias acteoside tawm tsam IL-1 -induced catabolic cuam tshuam xws li kev qhia ntawm pob txha mos-degrading enzymes thiab tsim cov proinflammatory cytokines thiab inflammatory mediators los ntawm inactivation ntawm cellular signaling pathways xws li NQBK thiab MAPK. thawj nas chondrocytes. Tsis ntev los no, zoo ib yam li peb txoj kev tshawb fawb, Qiao li al. tau tshaj tawm tias acteoside inhibits inflammatory teb nyob rau hauv OA-induced tsiaj [55]. Lawv tau qhia txog kev tawm tsam ntawm cytokines inflammatory cytokines los ntawm kev tsis ua haujlwm ntawm JAK / STAT signaling txoj hauv kev hauv cov ntaub so ntswg ntawm DMM-induced OA tsiaj uas tau txhaj tshuaj intraperitoneal ntawm acteoside [55]. Txawm li cas los xij, txhawm rau kwv yees qhov ua tau zoo ntawm acteoside raws li kev tiv thaiv OA ntxiv, acteoside tau hais lus rau DMM-induced OA tsiaj hauv txoj kev tshawb no. Tom qab ntawd, qhov kev hloov pauv ntawm cov pob txha mos tau raug soj ntsuam raws li pom hauv daim duab 9. Peb qhov kev ntsuam xyuas histological tau pom tias kev tswj hwm ntawm qhov ncauj ntawm acteoside tsis tu ncua tiv thaiv qhov kev loj hlob ntawm cov pob txha mos los ntawm kev inhibition ntawm proteoglycan poob hauv DMM-induced OA tsiaj.

5. Cov lus xaus

Peb qhov kev tshawb pom qhia tias acteoside muaj peev xwm tswj hwm qhov ncauj thiab tuaj yeem siv los ua cov tshuaj tiv thaiv zoo los tiv thaiv lossis txo qis OA raws li kev nyab xeeb lom neeg thiab cov tshuaj tiv thaiv kab mob tiv thaiv kab mob proinflammatory cytokines.

Cov ntaub ntawv

Cov ntaub ntawv muaj

Cov ntaub ntawv siv los txhawb qhov kev tshawb pom ntawm qhov kev tshawb fawb no muaj los ntawm tus kws sau ntawv raws li kev thov.

Kev pom zoo rau kev ncaj ncees

Thawj cov nas chondrocytes raug cais tawm ntawm cov pob txha mos ntawm cov nas ({{{{0}}}hnub nyoog; Sprague–Dawley) pob qij txha, raws li txoj cai (CIACUC2019-A0027) pom zoo los ntawm Lub Tsev Haujlwm Tsiaj Saib Xyuas thiab Siv Pawg ntawm Chosun University, Gwangju, Republic of Kauslim. Txhawm rau tsim cov tsiaj osteoarthritic, medial meniscus (DMM) tau raug phais hauv lub hauv caug pob qij txha ntawm BALB/c nas (qhov nruab nrab lub cev hnyav 19:3 ± 0:5g) raws li IACUC cov lus qhia (CIACUC2019-A0029).

Kev tsis sib haum xeeb

Cov kws sau ntawv tshaj tawm tias tsis muaj kev cuam tshuam ntawm kev txaus siab txog kev tshaj tawm ntawm kab lus no.

Cov neeg sau ntawv koom tes

HL, THK, KRK, JYS, HWK, thiab GUJ tau ua qhov kev ntsuam xyuas ntawm tes, ex vivo assay, hauv vivo assay siv tsiaj qauv, kev npaj cov ntaub ntawv, thiab cov ntawv sau. DKK, SSC, YY, YYC, JTL, CJO, DSO, thiab HSC tau ua cov ntaub ntawv txhais, sau ntawv, tshuaj xyuas, thiab kho. JSK tau tsim thiab ua raws li kev saib xyuas, kev tshawb nrhiav, kev tshuaj xyuas, kev tsim qauv, thiab sau ntawv, tshuaj xyuas, thiab kho. Hyang Lim thiab Do Kyung Kim tau pab tib yam rau txoj kev kawm no.

Kev lees paub

Txoj kev tshawb no tau txais kev txhawb nqa los ntawm Lub Tsev Haujlwm Saib Xyuas Kev Ua Liaj Teb Kauslim (2019141A00-1921-AB02), koom pheej ntawm Kaus Lim Kauslim.

acteosidehauvcistanchetuaj yeem txhim kho kev tiv thaiv kab mob

Cov ntaub ntawv

[1] Chen, J. W. Zhao, W. W. Han, H. J. Hamilton, H. J. Kuv, "Osteoarthritis: rau kev nkag siab zoo ntawm cov txheej txheem pathological," Bone Research, vol. 5, nre. 1, 2017.

[2] G. Musumeci, FC Aiello, MA Szychlinska, M. Di Rosa, P. Castrogiovanni, thiab A. Mobasheri, "Osteoarthritis nyob rau hauv lub xyoo pua XXI: kev pheej hmoo thiab kev coj cwj pwm uas cuam tshuam cov kab mob pib thiab kev loj hlob," International Journal of Molecular Sciences, vol. 16, nr. 12, pp. 6093–6112, 2015.

[3] A. Ghouri thiab PG Conaghan, "Kev Pom Zoo rau Kev Kho Mob hauv Osteoarthritis," Calcific Tissue International, 2020.

[4] B. Klimek, "6′-0-Apiosyl-verbascoside in the flower of mullein (Verbascum species)," Acta Poloniae Pharmaceutica, vol. 5 3, nr. 2 Ib., 137–140, 1996.

[5] F. Pardo, F. Perich, L. Villarroel, thiab R. Torres, "Kev rho tawm ntawm verbascoside, ib qho tshuaj tiv thaiv kab mob ntawm Buddleja globosa nplooj," Phau ntawv Journal of Ethnopharmacology, vol. 3 9, nr. 3, nr 3, 1993.

[6] JG Henn, L. Stefens, ND de Moura Sperotto, et al., "Toxicological evaluation of a standardized hydroethanolic extract from leaf of Plantago australis and its major compound, verbascoside," Journal of Ethnopharmacology, vol. 229 Ib., 145–156, 2019.

[7] M. Khullar, A. Sharma, A. Wani, thiab al., "Acteoside ameliorates inflammatory teb los ntawm NFkB txoj hauv kev haus cawv vim kev puas siab puas ntsws," International Immunopharmacology, vol. 69 Ib., 109–117, 2019.

[8] TW Hwang, DH Kim, DB Kim et al., "Synergistic anticancer effect of acteoside and temozolomide-based glioblastoma chemotherapy," International Journal of Molecular Medicine, vol. 4 3, nr. 3 Ib., 1478–1486, 2019.

[9] X. Li, Y. Xie, K. Li et al., "Antioxidation and cytoprotection of acteoside and its derivatives: comparison and mechanistic chemistry," Molecules, vol. 23, nr. 2 ib,p. 498 Peb 2018.

[10] M. Li, F. Zhou, T. Xu, H. Song, and B. Lu, "Acteoside tiv thaiv 6-OHDA-induced dopaminergic neuron kev puas tsuaj los ntawm Nrf2-TSIS qhia txoj hauv kev, " Food and Chemical Toxicology, vol. 119, p. 6–13, 2018.

[11] LF Santos-Cruz, JG Ávila-Acevedo, D. Ortega-Capitaine, thiab al., "Verbascoside tsis yog genotoxic nyob rau hauv ST thiab HB crosses ntawm Drosophila tis qhov chaw kuaj, thiab nws cov constituent, caféic acid, txo qhov Kev hloov pauv hloov pauv hloov pauv nyob rau hauv ST cross, "Food and Chemical Toxicology, vol. 50, nr. 3-4, p. 1082–1090, 2012.

[12] K. Negoro, S. Kobayashi, K. Takeno, K. Uchida, thiab H. Baba, "Kev cuam tshuam ntawm osmolarity ntawm glycosaminoglycan ntau lawm thiab cell metabolism ntawm articular chondrocyte nyob rau hauv peb-dimensional kab lis kev cai system," Clinical thiab sim Rheumatology, vol. 26, nr. 4, pp. 534–541, 2008.

[13] JS You, IA Cho, KR Kang, et al., "Coumestrol counteracts interleukin-1 -induced catabolic effects los ntawm suppressing inflammation in first rat chondrocytes," Inflammation, vol. 40, nr. 1, pp. 79–91, 2017.

[14] C. Pauli, R. Whiteside, FL Heras, et al., "Kev sib piv ntawm cov pob txha mos histopathology kev ntsuam xyuas ntawm tib neeg lub hauv caug pob qij txha ntawm txhua theem ntawm kev txhim kho osteoarthritis," Osteoarthritis thiab pob txha mos, vol. 20, nr. 6, pp. 476–485, 2012.

[15] FMD Henson thiab TA Vincent, "Kev hloov pauv hauv vimentin cytoskeleton hauv kev teb rau ib qho kev cuam tshuam rau hauv ib qho hauv vitro qauv ntawm pob txha mos hauv cov nas," BMC Musculoskeletal Disorders, vol. 9, nre. 1 ib,p. Peb 94, 2008.

[16] C. Corciulo thiab BN Cronstein, "Signaling of the purinergic system in the joint," Frontiers in Pharmacology, vol. 10 ib,p. Peb Hlis 1591, 2019.

[17] T. Neogi, "Cov kab mob sib kis thiab cuam tshuam ntawm qhov mob hauv osteoarthritis," Osteoarthritis thiab pob txha mos, vol. 21, nr. 9 Ib., 1145–1153, 2013.

[18] AC Hall, "Lub luag hauj lwm ntawm chondrocyte morphology thiab ntim hauv kev tswj phenotype-cuam tshuam rau osteoarthritis, pob txha kho, thiab pob txha mos engineering," Tam sim no Rheumatology Reports, vol. 21, nr. 8 ib,p. Peb Hlis 38, 2019.

[19] DJ Leong, JA Hardin, NJ Cobelli, thiab HB Sun, "Mechanotransduction thiab pob txha mos kev ncaj ncees," Annals ntawm New York Academy of Sciences, vol. 1240, Nr. 1, pp. 32–37, 2011.

[20] M. Kapoor, J. Martel-Pelletier, D. Lajeunesse, JP Pelletier, thiab H. Fahmi, "Lub luag hauj lwm ntawm proinflammatory cytokines nyob rau hauv lub pathophysiology ntawm osteoarthritis," Nature Reviews Rheumatology, vol. 7, nre. 1, pp. 33–42, 2011.

[21] Y. Henrotin thiab A. Mobasheri, "Cov khoom ntuj tsim los txhawb kev sib koom tes kev noj qab haus huv thiab tswj osteoarthritis," Tam sim no Rheumatology Reports, vol. 20, nr. 11 Ib., p. Peb Hlis 72, 2018.

[22] J. He, XP Hu, Y. Zeng, et al., "Kev tshawb fawb siab heev ntawm acteoside rau chemistry thiab bioactivities," Journal of Asian Natural Products Research, vol. 13, nr. 5, pp. 449–464, 2011.

[23] . 19, nr. 1, pp. 54–61, 2016.

[24] A. Perucatti, V. Genualdo, A. Pauciullo, et al., "Cytogenetic tests qhia tsis muaj toxicity hauv lymphocytes ntawm luav (Oryctolagus cuniculus, 2n{2}}) pub nyob rau hauv muaj verbascoside thiab/los yog lycopene, " Food and Chemical Toxicology, vol. 114, pp. 311–315, 2018.

[25] NG Thielen, PM van der Kraan, thiab AP van Caam, "TGFbeta/BMP signaling pathway in cartilage homeostasis," Cell, vol. Peb Hlis 8, 2019.

[26] E.-SE Mehana, AF Khafaga, thiab SS El-Blehi, "Lub luag haujlwm ntawm matrix metalloproteinases hauv osteoarthritis pathogenesis: kev tshuaj xyuas tshiab," Life Sciences, vol. Peb Hlis 234, 2019.

[27] C. Thorson, K. Galicia, A. Burleson, et al., "Matrix metalloproteinases thiab lawv cov inhibitors thiab proteoglycan 4 nyob rau hauv cov neeg mob nyob rau hauv tag nrho cov kev sib koom tes arthroplasty," Clinical thiab Applied Thrombosis / Hemostasis, vol. Peb Hlis 25, 2019.

[28] YY Chow and K.Y. Chin, "Lub luag hauj lwm ntawm o nyob rau hauv lub pathogenesis ntawm osteoarthritis," Mediators of Inflammation, vol. 2020, Tshooj ID 8293921, 19 nplooj ntawv, 2020.

[29] K. Sasaki, T. Hattori, T. Fujisawa, K. Takahashi, H. Inoue, thiab M. Takigawa, "Nitric oxide mediates interleukin-1-induced gene expression of matrix metalloproteinases and basic fibro-blast growth. qhov tseem ceeb hauv kab lis kev cai luav articular chondrocytes," Phau ntawv Journal of Biochemistry, vol. 123, Nr. 3, nr 431–439, 1998.

[30] R. Googs, SD Carter, G. Schulze-Tanzil, M. Shakibaei, thiab A. Mobasheri, "Apoptosis thiab poob ntawm chondrocyte survival signals contribute to articular cartilage degradation in osteoarthritis," Veterinary Journal, vol. 166, Nr. 2, pp. 140–158, 2003.

[31] M. Rahmati, A. Mobasheri, thiab M. Mozafari, "Inflammatory mediators in osteoarthritis: a critical review of the state-of-the-art, tam sim no prospects, and future challenges," Pob txha, vol. 85, pp. 81–90, 2016.

[32] J.-N. Gouze, E. Gouze, MP Popp, thiab al., "Exogenous glucosamine ntiaj teb no tiv thaiv chondrocytes los ntawm arthritogenic cuam tshuam ntawm IL-1beta," Arthritis Research & Therapy, vol. 8, nre. 6 ,ua p. R173, 2006.

[33] RX Zhang, K. Ren, thiab R. Dubner, "Osteoarthritis mob mechanisms: cov kev tshawb fawb hauv cov qauv tsiaj," Osteoarthritis thiab pob txha mos, vol. 21, nr. 9 Ib., 1308–1315, 2013.

[34] HJ I'm, JS Kim, X. Li et al., "Kev hloov pauv ntawm kev hnov ​​​​mob neurons thiab qaum teb rau kev sim osteoarthritis mob qauv," Arthritis thiab Rheumatism, vol. 62, Nr. 10, pp. 2995–3005, 2010.

[35] F. Wu, R. Zhang, X. Shen, thiab L. Lao, "Kev tshawb fawb ua ntej ntawm kev txo qhov mob ntawm monosodium iodoacetate-induced hauv caug osteoarthritis hauv nas los ntawm carbon dioxide laser moxibustion," Cov pov thawj-raws li Complementary thiab lwm yam tshuaj, vol. 2014, Tshooj ID 754304, 7 nplooj ntawv, 2014.

[36] NA Sims and NC Walsh, "GP130 cytokines and pob txha remodeling in health and disease," BMB Reports, vol. 4 3, nr. 8, pp. 513–523, 2010.

[37] C. Montagnoli, R. Tiribuzi, L. Crispoltoni, et al., "-NGF thiab -NGF receptor upregulation nyob rau hauv cov ntshav thiab synovial fluid nyob rau hauv osteoarthritis," Biological Chemistry, vol. 398, Nr. 9 Ib., 1045–1054, 2017.

[38] M. Miyagi, T. Ishikawa, H. Kamoda, et al., "Txoj kev loj hlob ntawm paj hlwb antibody nyob rau hauv lub hauv caug osteoarthritis mob qauv hauv nas," BMC Musculoskeletal Disorders, vol. 18, nr. 1 ib,p. 428 Peb 2017.

[39] F. Berenbaum, "Targeting paj paj loj hlob zoo los txo qhov mob ntawm osteoarthritis: peb tuaj yeem xav li cas?" Pob txha, Pob txha, vol. 86, nr. 2, p. 127-128, 2019.

[40] RE Miller, JA Block, thiab AM Malfait, "Nerve growth factor blockade for the management of osteoarthritis pain: peb kawm tau dab tsi los ntawm kev sim tshuaj thiab cov qauv preclinical?" Kev xav tam sim no hauv Rheumatology, vol. 29, nr. 1, pp. 110–118, 2017.

[41] LJ Sandell, X. Xing, C. Franz, S. Davies, LW Chang, and D. Patra, "Exuberant expression of chemokine genes by adult human articular chondrocytes in response to IL-1beta," Osteoarthritis thiab pob txha mos, vol. 16, nr. 12, pp. 1560–1571, 2008.

[42] IA Cho, TH Kim, H. Lim, et al., "Formononetin antagonizes the interleukin-1 -induced catabolic effects los ntawm suppressing inflammation in first rat chondrocytes," Inflammation, vol. 4 2, nr. 4 Ib., 1426–1440, 2019.

[43] SM Hou, CH Hou, thiab JF Liu, "CX3CL1 txhawb MMP-3 ntau lawm ntawm CX3CR1, c-Raf, MEK, ERK, thiab NF-κBsignaling txoj hauv kev osteoarthritis synovial broblasts," Kev Tshawb Fawb & Kev Kho Mob , vol. 19, nr. 1 ib,p. Peb Hlis 282, 2017.

[44] L. Zhao, Q. Wang, C. Zhang, thiab C. Huang, "Genome-wide DNA methylation analysis of articular chondrocytes identifies TRAF1, CTGF, and CX3CL1 genes as hypomethylated in osteoarthritis," Clinical Rheumatology, vol. 3 6, nr. 10 Ib., 2335–

2342, 2017.

[45] Y.-k. Xu, Y. Ke, B. Wang, J. H. Lin, "Lub luag haujlwm ntawm MCP-1-CCR2 ligand-receptor axis hauv chondrocyte degradation thiab kab mob kev loj hlob hauv lub hauv caug osteoarthritis," Biological Research, vol. 48, Nr. 1 ib,p. Peb 64, 2015.

[46] N. Alaaeddine, J. Antoniou, M. Moussa, et al., "The chemokine CCL20 induces proinflammatory and matrix degradative responses in cartilage," Inflammation Research, vol. 64, Nr. 9 Ib., 721–731, 2015.

[47] MW Hamrick, S. Herberg, P. Arounleut, et al., "Lub adipokine leptin ua rau cov leeg nqaij pob txha thiab tseem ceeb hloov cov leeg pob txha miRNA qhia txog cov nas muaj hnub nyoog,"Biochemical thiab Biophysical Research Communications, vol. 400, Nr. 3, pp. 379–383, 2010.

[48] ​​JH Ku, CK Lee, BS Joo, et al., "Correlation of synovial fluid leptin concentrations with the severity of osteoarthritis," Clinical Rheumatology, vol. 28, nr. 12, pp. 1431–1435, 2009.

[49] M. Yan, J. Zhang, H. Yang, thiab Y. Sun, "Lub luag hauj lwm ntawm leptin hauv osteoarthritis," Tshuaj (Baltimore), vol. 9 7,nr. 14, xov e0257, 2018.

[50] FPB Kroon, AI Veenbrink, R. de Mutsert, et al., "Lub luag hauj lwm ntawm leptin thiab adiponectin ua tus neeg nruab nrab hauv kev sib raug zoo ntawm adiposity thiab tes thiab lub hauv caug osteoarthritis," Osteoarthritis thiab pob txha mos, vol. 27, nrr. 12 Ib., 1761–1767, 2019.

[51] YH Gao, CW Zhao, B. Liu, et al., "Ib qho hloov tshiab ntawm kev koom tes ntawm metabolic syndrome thiab osteoarthritis thiab ntawm lub luag haujlwm ntawm leptin hauv osteoarthritis," Cytokine, vol. 129 Ib., p. 155043 Peb 2020.

[52] AJ Acuna, LT Samuel, SH Jeong, AK Emara, thiab AFKamath, "Viscosupplementation rau hip osteoarthritis: Puas yog kev tshuaj xyuas cov neeg mob tau tshaj tawm cov txiaj ntsig kev ntsuas txhawb kev siv?" Phau ntawv Journal of Orthopaedics, vol. 21 Ib., 137–149, 2020.

[53] J. Sokolove thiab CM Lepus, "Lub luag hauj lwm ntawm kev mob hauv lub pathogenesis ntawm osteoarthritis: cov kev tshawb pom tshiab thiab kev txhais lus," Therapeutic Advances in Musculoskeletal Disease, vol. 5, nre. 2, pp. 77–94, 2013.

[54] P. Wojdasiewicz, Ł. A. Poniatowski, thiab D. Szukiewicz, "Lub luag hauj lwm ntawm inflammatory thiab anti-inflammatory cytokines nyob rau hauv lub pathogenesis ntawm osteoarthritis," Mediators ntawm Inflammation, vol. 2014, Tshooj ID 561459, 19 nplooj ntawv, 2014.

[55] Z. Qiao, J. Tang, W. Wu, J. Tang, and M. Liu, "Acteoside inhibits inflammatory response of JAK/STAT signaling pathway in osteoarthritic nas," BMC Complementary and Alternative Medicine, vol. 19, nr. 1 ib,p. Peb Hlis 264, 2019.