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中华关节外科杂志(电子版) ›› 2024, Vol. 18 ›› Issue (03) : 352 -362. doi: 10.3877/cma.j.issn.1674-134X.2024.03.008

综述

基于骨关节炎软骨细胞表型转化的新兴治疗靶点
张刚1, 秦勇2, 黄超2, 薛震2, 吕松岑2,()   
  1. 1. 150086 哈尔滨医科大学附属第二医院关节与运动医学外科;150010 哈尔滨市第一医院骨科
    2. 150086 哈尔滨医科大学附属第二医院关节与运动医学外科
  • 收稿日期:2024-01-02 出版日期:2024-06-01
  • 通信作者: 吕松岑
  • 基金资助:
    2022年“新时代龙江优秀硕士、博士论文”资助项目(LJYXL2022-071); 2021年度国家骨科与运动康复临床医学研究中心(2021-NCRC-CXJJ-PY-20)

Emerging therapeutic targets based on phenotypic transformation of osteoarthritic chondrocytes

Gang Zhang1, Yong Qin2, Chao Huang2, Zhen Xue2, Songcen Lyu2,()   

  1. 1. Department of Joint and Sports Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China;Department of Orthopedics, Harbin First Hospital, Harbin 150010, China
    2. Department of Joint and Sports Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
  • Received:2024-01-02 Published:2024-06-01
  • Corresponding author: Songcen Lyu
引用本文:

张刚, 秦勇, 黄超, 薛震, 吕松岑. 基于骨关节炎软骨细胞表型转化的新兴治疗靶点[J]. 中华关节外科杂志(电子版), 2024, 18(03): 352-362.

Gang Zhang, Yong Qin, Chao Huang, Zhen Xue, Songcen Lyu. Emerging therapeutic targets based on phenotypic transformation of osteoarthritic chondrocytes[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2024, 18(03): 352-362.

骨关节炎(OA)是导致关节疼痛与功能障碍的主要疾病之一。OA的病理改变主要是软骨细胞的变性。自噬和凋亡是软骨细胞维持内稳态的重要机制,在OA中发挥着至关重要的作用。氧化应激在调节OA软骨细胞凋亡和自噬方面发挥着重要作用。在OA中,软骨细胞的衰老会导致关节软骨退变,加速疾病的进展。由于代谢失衡和软骨细胞功能异常,软骨细胞表型从稳定状态转变为肥大状态,基质金属蛋白酶水平增加,最终导致软骨细胞的永久性损伤。随着OA的进展,软骨细胞表型也会相应地发生改变,不同表型的细胞在形态和功能方面都会有显著差异。OA是一种异质性关节紊乱,目前仍缺乏有临床转化价值的药物问世。本文总结了近年来关于OA发病机制中软骨细胞的表型转化及相关治疗靶点的新进展,为未来在临床上调节软骨细胞表型转化和更有效地治疗OA提供新策略。

Osteoarthritis (OA) is one of the major diseases that cause joint pain and dysfunction.The pathological changes of OA mainly focus on apoptosis and dysfunction of chondrocytes. Autophagy and apoptosis are important mechanisms for maintaining homeostasis of chondrocytes and play a crucial role in OA. Oxidative stress plays an important role in regulating apoptosis and autophagy of OA chondrocytes. In OA, Aging of chondrocytes can lead to degeneration of articular cartilage. Due to metabolic imbalance and abnormal chondrocyte function, the chondrocyte phenotype transitions from a stable state to a hypertrophic state. This transition is accompanied by an increase in matrix metalloproteinase levels, ultimately resulting in permanent damage to chondrocytes. With the progression of OA, the chondrocyte phenotype will also change accordingly, and cells with different phenotypes will have significant differences in morphology and function. OA is a heterogeneous joint disorder, and there is still a lack of drugs with clinical translational value. This paper summarized the new progress in chondrocyte phenotype transformation and related therapeutic targets in the pathogenesis of OA in recent years, which may provide novel strategies for regulating chondrocyte phenotype transition and more effectively treating OA in the future.

图1 凋亡和自噬在OA(骨关节炎)发生发展中的作用
Figure 1 The role of autophagy and apoptosis in the development of OA
图2 肥大和衰老表型在OA(骨关节炎)发生发展中的作用
Figure 2 The development of hypertrophy and senescence phenotypes in chondrocytes
图3 不同的细胞及其表型参与OA的发病机制18
Figure 3 Diferent cells and their phenotypes participate in the pathogenesis of OA
[1]
Safiri SKolahi AASmith E,et al. Global,regional and national burden of osteoarthritis 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017[J]. Ann Rheum Dis2020,79(6): 819-828.
[2]
Hadzic EBeier F. Emerging therapeutic targets for osteoarthritis[J]. Expert Opin Ther Targets2023,27(2): 111-120.
[3]
Bannuru RROsani MCVaysbrot EE,et al. OARSI guidelines for the non-surgical management of knee,hip,and polyarticular osteoarthritis[J]. Osteoarthritis Cartilage2019,27(11): 1578-1589.
[4]
Messina ODVidal Wilman MVidal Neira LF. Nutrition,osteoarthritis and cartilage metabolism[J]. Aging Clin Exp Res2019,31(6): 807-813.
[5]
Jeon OHDavid NCampisi J,et al. Senescent cells and osteoarthritis: a painful connection[J]. J Clin Invest2018,128(4): 1229-1237.
[6]
Coryell PRDiekman BOLoeser RF. Mechanisms and therapeutic implications of cellular senescence in osteoarthritis[J]. Nat Rev Rheumatol2021,17(1): 47-57.
[7]
Makarczyk MJGao QHe Y,et al. Current models for development of disease-modifying osteoarthritis drugs[J]. Tissue Eng Part C Methods2021,27(2): 124-138.
[8]
Klionsky DJPetroni GAmaravadi RK,et al. Autophagy in major human diseases[J/OL]. EMBO J2021,40(19): e108863. DOI: 10.15252/embj.2021108863.
[9]
曹燕,李雪萍. 氧化应激在骨关节炎中的研究进展[J]. 医学综述2021,27(19): 3779-3784.
[10]
曾惠琼,邹玲华,尹志华,等. 自噬机制在骨关节炎中的作用[J]. 中华生物医学工程杂志2021,27(4): 453-460.
[11]
Li YSZhang FJZeng C,et al. Autophagy in osteoarthritis[J]. Joint Bone Spine2016,83(2): 143-148.
[12]
Ansari MYBall HCWase SJ,et al. Lysosomal dysfunction in osteoarthritis and aged cartilage triggers apoptosis in chondrocytes through BAX mediated release of Cytochrome C[J]. Osteoarthritis Cartilage2021,29(1): 100-112.
[13]
Wang CYao ZZhang Y,et al. Metformin mitigates cartilage degradation by activating AMPK/SIRT1-mediated autophagy in a mouse osteoarthritis model[J/OL]. Front Pharmacol2020,11: 1114. DOI: 10.3389/fphar.2020.01114.
[14]
Ma LLiu YZhao X,et al. Rapamycin attenuates articular cartilage degeneration by inhibiting β-catenin in a murine model of osteoarthritis[J]. Connect Tissue Res2019,60(5): 452-462.
[15]
Liu YLi XJin A. Rapamycin inhibits nf-ΚB activation by autophagy to reduce catabolism in human chondrocytes[J]. J Invest Surg2020,33(9): 861-873.
[16]
De Luna-Preitschopf AZwickl HNehrer S,et al. Rapamycin maintains the chondrocytic phenotype and interferes with inflammatory cytokine induced processes[J/OL]. Int J Mol Sci2017,18(7): 1494. DOI: 10.3390/ijms18071494.
[17]
Wang SDeng ZMa Y,et al. The role of autophagy and mitophagy in bone metabolic disorders[J]. Int J Biol Sci2020,16(14): 2675-2691.
[18]
Liu ZWang TSun X,et al. Autophagy and apoptosis: regulatory factors of chondrocyte phenotype transition in osteoarthritis[J]. Hum Cell2023,36(4): 1326-1335.
[19]
Xiao SQCheng MWang L,et al. The role of apoptosis in the pathogenesis of osteoarthritis[J]. Int Orthop2023,47(8): 1895-1919.
[20]
左显锋,范建楠,莫愁,等. 骨性关节炎关节软骨细胞凋亡的研究进展[J]. 山东医药2022,62(4): 108-111.
[21]
Mobasheri ABatt M. An update on the pathophysiology of osteoarthritis[J]. Ann Phys Rehabil Med2016,59(5-6): 333-339.
[22]
Park DRKim JKim GM,et al. Osteoclast-associated receptor blockade prevents articular cartilage destruction via chondrocyte apoptosis regulation[J/OL]. Nat Commun2020,11(1): 4343. DOI: 10.1038/s41467-020-18208-y.
[23]
Wang BShao ZGu M,et al. Hydrogen sulfide protects against IL-1β-induced inflammation and mitochondrial dysfunction-related apoptosis in chondrocytes and ameliorates osteoarthritis[J]. J Cell Physiol2021,236(6): 4369-4386.
[24]
Xu KHe YMoqbel SAA,et al. SIRT3 ameliorates osteoarthritis via regulating chondrocyte autophagy and apoptosis through the PI3K/Akt/mTOR pathway[J]. Int J Biol Macromol2021,175: 351-360.
[25]
He YFan LAaron N,et al. Reduction of Smad2 caused by oxidative stress leads to necrotic death of hypertrophic chondrocytes associated with an endemic osteoarthritis[J]. Rheumatology2021,61(1): 440-451.
[26]
Duan RXie HLiu ZZ. The role of autophagy in osteoarthritis[J/OL]. Front Cell DevBiol2020,8: 608388. DOI: 10.3389/fcell.2020.608388.
[27]
Jiang SLiu YXu B,et al. Noncoding RNAs: new regulatory code in chondrocyte apoptosis and autophagy[J/OL]. Wiley Interdiscip Rev RNA2020,11(4): e1584. DOI: 10.1002/wrna.1584.
[28]
徐伟,廖冬发,王娟,等. 细胞衰老在骨关节炎中作用的研究进展[J]. 中国矫形外科杂志2022,30(15): 1386-1390.
[29]
郭慧宁,凌霜,刘俊,等. 衰老相关分泌表型的研究进展[J]. 中国药理学通报2016,32(11): 1505-1509.
[30]
Jeon OHKim CLaberge RM,et al. Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment[J]. Nat Med2017,23(6): 775-781.
[31]
Loeser RFCollins JADiekman BO. Ageing and the pathogenesis of osteoarthritis[J]. Nat Rev Rheumatol2016,12(7): 412-420.
[32]
Rim YANam YJu JH. The role of chondrocyte hypertrophy and senescence in osteoarthritis initiation and progression[J/OL]. Int J Mol Sci2020,21(7): 2358. DOI: 10.3390/ijms21072358.
[33]
Singh PMarcu KBGoldring MB,etal. Phenotypic instability of chondrocytes in osteoarthritis: on a path to hypertrophy[J]. Ann N Y Acad Sci2019,1442(1): 17-34.
[34]
袁长深,李哲,韦晓芸,等. 骨关节炎细胞自噬机制的相关药物研究进展[J]. 医学综述2022,28(4): 783-789.
[35]
胡浩然,谢雪涛,张长青. 骨关节炎中软骨细胞自噬的研究进展[J/CD]. 中华关节外科杂志(电子版)2018,12(6): 826-829.
[36]
Zheng GZhan YLi X,et al. TFEB,a potential therapeutic target for osteoarthritis via autophagy regulation[J/OL]. Cell Death Dis2018,9(9): 858. DOI: 10.1038/s41419-018-0909-y.
[37]
Zhou JWang YLiu Y,et al. Adipose derived mesenchymal stem cells alleviated osteoarthritis and chondrocyte apoptosis through autophagy inducing[J]. J Cell Biochem2019,120(2): 2198-2212.
[38]
Ge YZhou SLi Y,et al. Estrogen prevents articular cartilage destruction in a mouse model of AMPK deficiency via ERK-mTOR pathway[J/OL]. Ann Transl Med2019,7(14): 336. DOI: 10.21037/atm.2019.06.77.
[39]
Wu JKuang LChen C,et al. MiR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis[J]. Biomaterials2019,206: 87-100.
[40]
钟培瑞,周君,廖源,等. 帕瑞昔布对膝骨关节炎大鼠关节软骨及软骨下骨的影响[J]. 中国矫形外科杂志2019,27(15): 1404-1409.
[41]
Maimaitijuma TYu JHRen YL,et al. PHF23 negatively regulates the autophagy of chondrocytes in osteoarthritis[J/OL]. Life Sci2020,253: 117750. DOI: 10.1016/j.lfs.2020.117750.
[42]
Sacitharan PKBou-Gharios GEdwards JR. SIRT1 directly activates autophagy in human chondrocytes[J/OL]. Cell Death Discov2020,6: 41. DOI: 10.1038/s41420-020-0277-0.
[43]
Kong CWang CShi Y,et al. Active vitamin D activates chondrocyte autophagy to reduce osteoarthritis via mediating the AMPK-mTOR signaling pathway[J]. Biochem Cell Biol2020,98(3): 434-442.
[44]
Lin ZMiao JZhang T,et al. JUNB-FBXO21-ERK axis promotes cartilage degeneration in osteoarthritis by inhibiting autophagy[J/OL]. Aging Cell2021,20(2): e13306. DOI: 10.1111/acel.13306.
[45]
Xue SZhou XSang W,et al. Cartilage-targeting peptide-modified dual-drug delivery nanoplatform with NIR laser response for osteoarthritis therapy[J]. Bioact Mater2021,6(8): 2372-2389.
[46]
Sun KLuo JGuo J,et al. The PI3K/AKT/mTOR signaling pathway in osteoarthritis: a narrative review[J]. Osteoarthritis Cartilage2020,28(4): 400-409.
[47]
Lu JJi MLZhang XJ,et al. MicroRNA-218-5p as a potential target for the treatment of human osteoarthritis[J]. Mol Ther2017,25(12): 2676-2688.
[48]
Cai CMin SYan B,et al. MiR-27a promotes the autophagy and apoptosis of IL-1β treated-articular chondrocytes in osteoarthritis through PI3K/AKT/mTOR signaling[J]. Aging2019,11(16): 6371-6384.
[49]
Lin CShao YZeng C,et al. Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post-traumatic osteoarthritis[J]. J Cell Physiol2018,233(8): 6135-6147.
[50]
Hu PFChen WPBao JP,et al. Paeoniflorin inhibits IL-1β-induced chondrocyte apoptosis by regulating the Bax/Bcl-2/caspase-3 signaling pathway[J]. Mol Med Rep2018,17(4): 6194-6200.
[51]
Chen JGu YTXie JJ,et al. Gastrodin reduces IL-1β-induced apoptosis,inflammation,and matrix catabolism in osteoarthritis chondrocytes and attenuates rat cartilage degeneration in vivo[J]. Biomed Pharmacother2018,97: 642-651.
[52]
Khan NMAhmad IHaqqi TM. Nrf2/ARE pathway attenuates oxidative and apoptotic response in human osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling axis[J]. Free Radic Biol Med2018,116: 159-171.
[53]
Marchev ASDimitrova PABurns AJ,et al. Oxidative stress and chronic inflammation in osteoarthritis: can NRF2 counteract these partners in crime?[J]. Ann N Y Acad Sci2017,1401(1): 114-135.
[54]
Murahashi YYano FKobayashi H,et al. Intra-articular administration of IκBα kinase inhibitor suppresses mouse knee osteoarthritis via downregulation of the NF-κB/HIF-2α axis[J/OL]. Sci Rep2018,8(1): 16475. DOI: 10.1038/s41598-018-34830-9.
[55]
Wang PTeng SZhuang C,et al. Directed elimination of senescent cells attenuates development of osteoarthritis by inhibition of c-IAP and XIAP[J]. Biochim Biophys Acta Mol Basis Dis2019,1865(10): 2618-2632.
[56]
Jiang LXu KLi J,et al. Nesfatin-1 suppresses interleukin-1β-induced inflammation,apoptosis,and cartilage matrix destruction in chondrocytes and ameliorates osteoarthritis in rats[J]. Aging2020,12(2): 1760-1777.
[57]
Velard FChatron-Colliet ACôme D,et al. Adrenomedullin and truncated peptide adrenomedullin(22-52)affect chondrocyte response to apoptotis in vitro: downregulation of FAS protects chondrocyte from cell death[J/OL]. Sci Rep2020,10(1): 16740. DOI: 10.1038/s41598-020-73924-1.
[58]
Yang LWang ZZou C,et al. Ubiquitin-specific protease 49 attenuates IL-1β-induced rat primary chondrocyte apoptosis by facilitating Axin deubiquitination and subsequent Wnt/β-catenin signaling cascade inhibition[J]. Mol Cell Biochem2020,474(1-2): 263-275.
[59]
Dvir-Ginzberg MMobasheri AKumar A. The role of sirtuins in cartilage homeostasis and osteoarthritis[J/OL]. Curr Rheumatol Rep2016,18(7): 43. DOI: 10.1007/s11926-016-0591-y.
[60]
Zhao GWang HXu C,et al. SIRT6 delays cellular senescence by promoting p27Kip1 ubiquitin-proteasome degradation[J]. Aging2016,8(10): 2308-2323.
[61]
Collins JAKapustina MBolduc JA,et al. Sirtuin 6(SIRT6)regulates redox homeostasis and signaling events in human articular chondrocytes[J]. Free Radic Biol Med2021,166: 90-103.
[62]
Nagai KMatsushita TMatsuzaki T,et al. Depletion of SIRT6 causes cellular senescence,DNA damage,and telomere dysfunction in human chondrocytes[J]. Osteoarthritis Cartilage2015,23(8): 1412-1420.
[63]
Farr JNXu MWeivoda MM,et al. Targeting cellular senescence prevents age-related bone loss in mice[J]. Nat Med2017,23(9): 1072-1079.
[64]
Faust HJZhang HHan J,et al. IL-17 and immunologically induced senescence regulate response to injury in osteoarthritis[J]. J Clin Invest2020,130(10): 5493-5507.
[65]
Wu GZhang CXu L,et al. BAK plays a key role in A-1331852-induced apoptosis in senescent chondrocytes[J]. Biochem Biophys Res Commun2022,609: 93-99.
[66]
Ding DFXue YWu XC,et al. Recent advances in reactive oxygen species(ROS)-responsive polyfunctional nanosystems 3.0 for the treatment of osteoarthritis[J]. J Inflamm Res2022,15: 5009-5026.
[67]
Riegger JSchoppa ARuths L,et al. Oxidative stress as a key modulator of cell fate decision in osteoarthritis and osteoporosis: a narrative review[J/OL]. Cell Mol Biol Lett2023,28(1): 76. DOI: 10.1186/s11658-023-00489-y.
[68]
Ansari MYKhan NMAhmad I,et al. Parkin clearance of dysfunctional mitochondria regulates ROS levels and increases survival of human chondrocytes[J]. Osteoarthritis Cartilage2018,26(8): 1087-1097.
[69]
Deng ZLi YLiu H,et al. The role of sirtuin 1 and its activator,resveratrol in osteoarthritis[J/OL]. Biosci Rep2019,39(5): BSR20190189.DOI: 10.1042/BSR20190189.
[70]
Feng KChen ZLiu P,et al. Quercetin attenuates oxidative stress-induced apoptosis via SIRT1/AMPK-mediated inhibition of ER stress in rat chondrocytes and prevents the progression of osteoarthritis in a rat model[J]. J Cell Physiol2019,234(10): 18192-18205.
[71]
D’Adamo SCetrullo SGuidotti S,et al. Spermidine rescues the deregulated autophagic response to oxidative stress of osteoarthritic chondrocytes[J]. Free Radic Biol Med2020,153: 159-172.
[72]
Ji MLJiang HLi Z,et al. Sirt6 attenuates chondrocyte senescence and osteoarthritis progression[J/OL]. Nat Commun2022,13(1): 7658. DOI: 10.1038/s41467-022-35424-w.
[73]
Marcucci GDomazetovic VNediani C,et al. Oxidative stress and natural antioxidants in osteoporosis: novel preventive and therapeutic approaches[J/OL]. Antioxidants2023,12(2): 373. DOI: 10.3390/antiox12020373.
[74]
韩明睿,刘倩倩,孙洋. 骨关节炎发病机制及药物调控新进展[J]. 中国药理学通报2022,38(6): 807-812.
[75]
Gigout AGuehring HFroemel D,et al. Sprifermin(rhFGF18)enables proliferation of chondrocytes producing a hyaline cartilage matrix[J]. Osteoarthritis Cartilage2017,25(11): 1858-1867.
[76]
Nalesso GThomas BLSherwood JC,et al. WNT16 antagonises excessive canonical WNT activation and protects cartilage in osteoarthritis[J]. Ann Rheum Dis2017,76(1): 218-226.
[77]
Wu DJin SLin Z,et al. Sauchinone inhibits IL-1β induced catabolism and hypertrophy in mouse chondrocytes to attenuate osteoarthritis via Nrf2/HO-1 and NF-κB pathways[J]. Int Immunopharmacol2018,62: 181-190.
[78]
Yano FOhba SMurahashi Y,et al. Runx1 contributes to articular cartilage maintenance by enhancement of cartilage matrix production and suppression of hypertrophic differentiation[J/OL]. Sci Rep2019,9(1): 7666. DOI: 10.1038/s41598-019-43948-3.
[79]
Malfait AMTortorella MD. The “elusive DMOAD”: Aggrecanase inhibition from laboratory to clinic[J]. Clin Exp Rheumatol2019,37 Suppl 120(5): 130-134.
[80]
Latourte AKloppenburg MRichette P. Emerging pharmaceutical therapies for osteoarthritis[J]. Nat Rev Rheumatol2020,16(12): 673-688.
[81]
Chou HCChen CHChou LY,et al. Discoidin domain receptors 1 inhibition alleviates osteoarthritis via enhancing autophagy[J/OL]. Int J Mol Sci2020,21(19): 6991. DOI: 10.3390/ijms21196991.
[82]
Sun MMGBeier FPest MA. Recent developments in emerging therapeutic targets of osteoarthritis[J]. Curr Opin Rheumatol2017,29(1): 96-102.
[83]
Yi HZhang WCui ZM,et al. Resveratrol alleviates the interleukin-1β-induced chondrocytes injury through the NF-κB signaling pathway[J/OL]. J Orthop Surg Res2020,15(1): 424. DOI: 10.1186/s13018-020-01944-8.
[84]
Tanikella ASHardy MJFrahs SM,et al. Emerging gene-editing modalities for osteoarthritis[J/OL]. Int J Mol Sci2020,21(17): 6046. DOI: 10.3390/ijms21176046.
[85]
Seidl CIFulga TAMurphy CL. CRISPR-Cas9 targeting of MMP13 in human chondrocytes leads to significantly reduced levels of the metalloproteinase and enhanced type II collagen accumulation[J]. Osteoarthritis Cartilage2019,27(1): 140-147.
[86]
Karlsen TAPernas PFStaerk J,et al. Generation of IL1β-resistant chondrocytes using CRISPR-CAS genome editing[J/OL]. Osteoarthritis Cartilage2016,24: S325 DOI: 10.1016/j.joca.2016.01.581.
[87]
Zhao LHuang JFan Y,et al. Exploration of CRISPR/Cas9-based gene editing as therapy for osteoarthritis[J]. Ann Rheum Dis2019,78(5): 676-682.
[88]
Rassart EDesmarais FNajyb O,et al. Apolipoprotein D[J/OL]. Gene2020,756: 144874. DOI: 10.1016/j.gene.2020.144874.
[89]
Sanchez DGanfornina MD. The lipocalin apolipoprotein D functional portrait: asystematic review[J/OL]. Front Physiol2021,12: 738991. DOI: 10.3389/fphys.2021.738991.
[90]
Kurano MTsukamoto KKamitsuji S,et al. Apolipoprotein D modulates lipid mediators and osteopontin in an anti-inflammatory direction[J]. Inflamm Res2023,72(2): 263-280.
[91]
Fyfe-Desmarais GDesmarais FRassart É,et al. Apolipoprotein D in oxidative stress and inflammation[J/OL]. Antioxidants2023,12(5): 1027. DOI: 10.3390/antiox12051027.
[92]
Pascua-Maestro RCorraliza-Gomez MFadrique-Rojo C,et al. Apolipoprotein D-mediated preservation of lysosomal function promotes cell survival and delays motor impairment in Niemann-Pick type A disease[J/OL]. Neurobiol Dis2020,144: 105046. DOI: 10.1016/j.nbd.2020.105046.
[93]
Qin YLi JZhou Y,et al. Apolipoprotein D as a potential biomarker and construction of a transcriptional regulatory-immune network associated with osteoarthritis by weighted gene coexpression network analysis[J]. Cartilage2021,13(1_suppl): 1702S-1717S.
[94]
Xu WGu SZhang G,et al. APOD acts on fibroblast-like synoviocyte and chondrocyte to alleviate the process of osteoarthritis in vitro[J]. J Orthop Res2024,42(2): 296-305.
[95]
Ji QZheng YZhang G,et al. Single-cell RNA-seq analysis reveals the progression of human osteoarthritis[J]. Ann Rheum Dis2019,78(1): 100-110.
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