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摘要: 软骨的生长发育及骨关节炎进程十分复杂,同时受到多种生长因子、细胞因子、内外环境等因素影响,并由多条生物信号分子通路交叉调控,因此,其分子作用机制对于软骨发育和骨关节炎的诊治至关重要。长链非编码RNA(Long non-coding RNAs,LncRNAs)是一类转录本长度超过200个核苷酸的非编码RNA,在生物发育、基因表达以及表观遗传中发挥着复杂精确的调控作用,与人类疾病的发生、发展和防治具有密切关系。近年来,许多与软骨生长发育和炎症相关的lncRNAs被相继发现。通过对lncRNAs的分类、功能及其在软骨发育和炎症中的作用进行系统综述,发现多种lncRNAs参与了软骨生长发育和骨关节炎的发生与发展,调控相关lncRNAs的表达可减轻软骨炎症,减缓疾病进展。旨在为lncRNAs与软骨生长发育及骨关节炎的基础研究及临床应用提供科学的参考依据。Abstract: The growth and disease progression of cartilage are highly complex, influenced by various growth factors, cytokines, and both internal and external environmental factors. This process is regulated by multiple intersecting biological signaling pathways. Consequently, the study of its molecular mechanisms is crucial for the development and treatment of cartilage-related diseases. Long non-coding RNAs (lncRNAs) are a class of regulatory non-coding RNAs with transcript lengths exceeding 200 nucleotides. They play a complex and precise role in biological development, gene expression and epigenetics, and are closely associated with the onset, progression and prevention of human diseases. In recent years, numerous lncRNAs related to cartilage growth and disease have been discovered. This article systematically reviews the classification, function and mechanisms of action of lncRNAs in cartilage development and disease. It reveals that various lncRNAs are involved in the onset and progression of cartilage growth and diseases. Regulating the expression of relevant lncRNAs can alleviate cartilage inflammation and slow disease progression. This paper aims to provide a scientific basis for basic research and clinical application of lncRNAs in cartilage growth and disease.
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宫颈癌患病早期患者大都无明显临床症状,随病情进展,患者常会伴有异常阴道排液、接触性出血等表现。若未能及时采取有效的治疗措施,肿瘤会持续进展,侵犯临近组织,甚至发生远处转移,引起多器官功能障碍[1−2]。宫颈癌病程进展缓慢且病变过程复杂,若能够早期明确诊断并采取相关治疗,可改善患者预后。经阴道彩色多普勒超声是诊断宫颈病变的常用手段,能够全方位显示患者宫颈结构,便于医者发现病灶,并观察其形态、与周围组织关系等信息。同时,彩色多普勒血流成像模式有助于显示局部血供情况,可帮助临床诊断疾病[3−4]。相关研究指出,血管生成与癌细胞生长、繁殖、转移等存在密切联系[5]。因此,观察宫颈病变患者病灶局部血流信号对疾病诊断具有重要意义。Adler分级属半定量分级,是反映肿瘤内部血供情况、血流分布情况的重要指标,在甲状腺肿瘤、乳腺肿瘤等多种肿瘤疾病中应用广泛[6−7]。为进一步明确宫颈癌血流状况,本研究将彩色多普勒超声应用于宫颈癌患者,探讨Adler分级在诊断宫颈癌中的价值,并分析其与病理指标的相关性,以期为该病患者的诊治提供参考。
1. 资料与方法
1.1 病例资料
回顾性纳入2020年1月至2023年1月医院136例宫颈癌患者为宫颈癌组,另取同期医院80例宫颈良性病变患者为对照组。2组资料比较,均衡性良好(P > 0.05),具有可比性,见表1。
表 1 2组一般资料比较[n(%)/($ \bar x \pm s $)]Table 1. General data of 2 groups [n(%)/($ \bar x \pm s $)]指标 宫颈癌组(n=136) 对照组(n=80) t P 年龄(岁) 45.83±6.29 45.13±7.14 0.751 0.454 体重指数(kg/m2) 24.85±2.12 24.72±2.23 0.427 0.670 绝经情况 是 49(36.03) 26(32.50) 0.277 0.599 否 87(63.97) 54(67.50) 流产史 有 38(27.94) 19(23.75) 0.456 0.500 无 98(72.06) 61(76.25) 1.2 入组标准
纳入标准:(1)经病理组织检查确诊,符合宫颈癌诊断标准[8];(2)临床资料及影像学资料完整;(3)患者或家属自愿于知情书上签字。排除标准:(1)既往有放射治疗、化疗治疗史;(2)合并全身急慢性感染性疾病;(3)伴有免疫系统、血液系统疾病;(4)存在先天性子宫畸形;(5)合并重要器官功能障碍,如严重心、肾、肝等;(6)合并其他恶性肿瘤疾病;(7)既往有宫颈部手术史;(8)哺乳期或妊娠期女性;(9)合并认知障碍或精神疾病。本研究经过医院伦理审核(2019-002-01)。
1.3 方法
1.3.1 彩色多普勒超声检查
采用GE(美国)公司Voluson E10型彩色多普勒超声对受检者进行检查,配以Ic5-9-D超声探头,频率5~9 MHz。嘱咐受检者检查前排空膀胱,取截石位,在探头上涂抹耦合剂、套上隔离套经阴道缓慢置入宫颈,详细探查宫颈内口、宫颈外口、宫旁、宫颈管、肌层组织情况,行横向、纵向、斜向多切面扫查,观察有无肿块,若发现可疑病灶,详细记录其浸润范围及与周围组织关系;常规扫查完成后启用彩色多普勒血流成像模式,观察宫颈内部及周围血流情况,记录舒张末期流速(end diastolic velocity,EDV)、收缩期峰值流速(peak systolic velocity,PSV)、血流阻力指数(resistive index,RI)。
1.3.2 血流信号Adler分级
采用Adler半定量标准对血流信号进行分级,无明显血流信号视为0级;存在1~2处点状血流信号视为1级;存在2~3处条状或棒状血流信号视为2级;存在4处及4处以上条状、棒状血流信号,或血管交织呈网络状视为3级,见图1~图4。
1.4 观察指标
(1)对比宫颈癌组与对照组彩超图像特征,包括宫颈回声、宫颈大小(宫颈长度2~3 cm视为正常,宫颈长度>4 cm视为偏大)及Adler分级;(2)对比不同Adler分级的宫颈癌患者病理指标,包括临床分期(Ⅰ期:癌灶局限于宫颈;Ⅱ期:癌灶超过宫颈但未达到盆壁,癌灶累及阴道,但未达到阴道下1/3;Ⅲ期:癌灶累及阴道下1/3,或(和)扩散至盆壁,存在肾功能障碍或肾盂积水;Ⅳ期:癌细胞向远处扩散超出骨盆,或癌细胞浸润直肠粘膜、膀胱黏膜)、淋巴结转移(是、否)、病理类型(鳞癌、腺癌)、宫旁浸润(是、否)、微血管密度(采集病变组织标本进行甲醛固定、石蜡包埋处理,切片,计数病变组织内的微血管密度。微血管判定标准:以棕褐色染色的细胞团或内皮细胞为独立计数单位,血管结构相连、血管周围平滑肌包绕、血管腔>8个红细胞面积不做独立计数。选择具有代表性的组织切片,低倍镜下选取3个微血管密集处,更换高倍镜对血管微血管密度进行计数,取平均值)、病灶最大直径、糖类抗原125(CA125)、糖类抗原199(CA199)。采集3 mL清晨空腹静脉血,离心10 min(离心温度为4 ℃,离心半径为6 cm,离心率为3000 r/min)分离血清,采用电化学发光法测定CA125、CA199水平,检测试剂盒选择罗氏公司产品)。
1.5 统计学处理
数据处理采用SPSS 23.0软件,计量资料以($ \bar x \pm s$)表示,以t检验;计数资料用n(%)表示,以χ2检验,等级资料采用秩和检验;绘制ROC分析彩超图像特征及Adler分级对宫颈癌的诊断价值;分类变量间相关性采用phi系数相关性分析检验;分类变量与连续变量间相关性采用点二列相关性分析检验,P < 0.05为差异有统计学意义。
2. 结果
2.1 宫颈癌组与对照组彩超图像特征及Adler分级
宫颈癌组宫颈高回声、宫颈等回声、宫颈偏大占比、Adler分级、PSV、EDV高于对照组,宫颈低回声、宫颈大小正常占比、RI低于对照组(P < 0.05),见表2。
表 2 宫颈癌组与对照组彩超图像特征及Adler分级[n(%)/($\bar x \pm s$)]Table 2. Color ultrasound image features and Adler grading of cervical cancer group and control group [n(%)/($ \bar x \pm s $)]指标 宫颈癌组(n=136) 对照组(n=80) Z/χ2/t P 宫颈回声 低回声 59(43.38) 69(86.25) χ2=42.234 <0.001* 等回声 42(30.88) 11(13.75) 高回声 35(25.74) 0 宫颈大小 正常 103(75.74) 74(92.50) χ2=9.568 0.002* 偏大 33(24.26) 6(7.50) Adler分级 0级 2(1.47) 71(88.75) Z=12.419 0.000* 1级 23(16.91) 9(11.25) 2级 78(57.35) 0 3级 33(24.26) 0 PSV(cm/s) 35.82±8.23 24.53±6.59 t=10.453 0.000* EDV(cm/s) 10.28±3.61 6.61±1.27 t=8.722 0.000* RI 1.07±0.26 1.43±0.46 t=7.352 0.000* *P < 0.05。 2.2 彩超图像特征及Adler分级对宫颈癌的诊断价值
将彩超图像特征(宫颈回声、宫颈大小、PSV、EDV、RI)、Adler分级作为检验变量,将宫颈癌发生情况作为状态变量(1=宫颈癌,0=宫颈良性病变患者),绘制ROC曲线(图5),结果显示:宫颈回声、宫颈大小、PSV、EDV、RI对宫颈癌具有一定诊断价值,Adler分级对宫颈癌具有较高诊断价值(AUC=0.758、0.590、0.902),见表3。
表 3 彩超图像特征及Adler分级对宫颈癌的诊断价值Table 3. Diagnostic value of color ultrasound image features and Adler grading for cervical cancer检验变量 AUC 标准误 P 95%CI 敏感度 特异度 约登指数 宫颈回声 0.714 0.035 0.000 0.645~0.784 0.566 0.763 0.329 宫颈大小 0.584 0.039 0.040 0.507~0.660 0.643 0.525 0.168 PSV 0.856 0.025 0.000 0.807~0.904 0.853 0.662 0.515 EDV 0.823 0.029 0.000 0.767~0.879 0.801 0.650 0.451 RI 0.765 0.038 0.000 0.690~0.839 0.735 0.675 0.410 Adler分级 0.852 0.028 0.000 0.797~0.907 0.816 0.887 0.703 2.3 不同Adler分级宫颈癌患者病理指标比较
2~3级组临床分期、微血管密度、PSV、EDV高于0~1级组,病灶最大直径长于0~1级组,RI低于0~1级组(P < 0.05);2组淋巴结转移、病理类型、宫旁浸润、CA125、CA199水平比较,差异不显著(P > 0.05),见表4。
表 4 不同Adler分级宫颈癌患者病理指标比较[n(%)/($\bar x \pm s$)]Table 4. Comparison of pathological indexes of cervical cancer patients with different Adler grades[n(%)/($ \bar x \pm s $)]指标 0~1级组(n=25) 2~3级组(n=111) Z/χ2/t P 临床分期 Ⅰ期 24(96.00) 26(23.42) 6.237 0.000* Ⅱ期 1(4.00) 64(57.66) Ⅲ期 0 13(11.71) Ⅳ期 0 8(7.21) 病理类型 鳞癌 19(76.00) 99(89.19) 2.049 0.152 腺癌 6(24.00) 12(10.81) 淋巴结转移 是 2(8.00) 19(17.12) 0.612 0.434 否 23(92.00) 92(82.88) 宫旁浸润 是 1(4.00) 13(11.71) 0.695 0.405 否 24(96.00) 98(88.29) 微血管密度 40.42±1.51 44.36±1.78 10.260 0.000* 病灶最大直径(mm) 28.93±9.54 40.62±12.17 4.497 0.000* CA125(U/mL) 10.25±3.14 14.56±3.42 1.755 0.082 CA199(U/mL) 10.21±2.46 10.63±3.28 0.602 0.548 PSV(cm/s) 25.52±5.86 38.14±7.69 7.708 0.000* EDV(cm/s) 6.77±1.89 11.07±2.06 9.566 0.000* RI 1.47±0.35 0.98±0.24 8.413 0.000* *P < 0.05。 2.4 Adler分级与病理指标的相关性分析
经Phi系数相关性分析,结果显示,Adler分级与临床分期呈正相关(Phi = 0.203,P = 0.018);经点二列相关性分析,结果显示:Adler分级与微血管密度、病灶最大直径、PSV、EDV呈正相关(r = 0.664、0.363,P均=0.000),与RI呈负相关(r = -0.597,P = 0.000),见表5。
表 5 Adler分级与病理指标的相关性分析Table 5. Correlation analysis between Adler grade and pathological indexes病理指标 Phi系数/r P 临床分期 0.203 0.018* 微血管密度 0.664 0.000* 病灶最大直径 0.363 0.000* PSV 0.554 0.000* EDV 0.635 0.000* RI −0.597 0.000* *P < 0.05。 3. 讨论
宫颈癌发病原因诸多,人乳头瘤病毒(human papillomavirus,HPV)持续感染是其主要诱因,且吸烟、多孕多产、性生活开始过早等也是引发宫颈癌的危险因素[9]。故早诊断、早治疗在改善患者生活质量中尤为关键。既往临床针对宫颈癌的筛查常通过肉眼观察、阴道镜、宫颈刮片细胞学检查,但上述检查方法较难发现宫颈肌层、宫颈管内病变,临床应用价值有限。
经阴道彩色多普勒超声检查具有软组织分辨率高、操作简单、可重复性强等优点,能够清晰显示宫颈各层结构,准确定位病变组织,并可为鉴别病变性质提供重要信息[10−11]。与常规腹部超声相比,经阴道彩超探头更加小巧灵活,能够更加贴近病灶,并从多个角度对目标部位进行不同深度的探测,从而更加清晰展现病灶具体形态[12]。本研究采用经阴道彩超检查宫颈癌患者,结果显示,与宫颈良性病变患者相比,宫颈癌患者宫颈高回声、宫颈等回声、宫颈偏大占比、PSV、EDV更高,宫颈低回声、宫颈大小正常占比、RI更低,表明阴道彩色超声可通过病灶组织回声、宫颈轮廓、宫颈形态、血流信息改变等判断宫颈癌发生情况。既往研究发现,新血管生成与宫颈癌细胞增殖、浸润、转移、上皮-间质转化等密切相关[13]。肿瘤生长过程中营养需求较高,会诱导多种新血管生成,丰富局部血流,为肿瘤组织生长提供丰富的血供,造成肿瘤内部及周围血流量显著增多,进而增加PSV、EDV;同时,新血管管壁较薄、分布凌乱,肿瘤组织快速生长过程中,血管管腔不规则扩张,极易形成“血管湖”,降低血流组织,表现为RI降低。
宫颈癌病变过程缓慢且复杂,从HPV感染发展至宫颈癌需经历宫颈上皮瘤变,研究发现,宫颈上皮瘤变发展至宫颈癌过程中患者机体血管形成因子逐渐增多,微血管密度不断增加,最终导致肿瘤血管、血流丰富,并对患者预后产生负性影响[14−15]。彩色多普勒超声利用超声探头与红细胞之间的相对运动产生频移显示血流信号,采用壁虑器消除运动伪影和杂波,有效捕捉血流信号,能够为医者提供真实的血流信息[16]。彩超Adler分级是临床评估肿瘤内部血流情况的常用指标,其分级越高则表明血管分布越广泛、血流供应越丰富[17−18]。本研究观察受检者Adler分级,结果显示,宫颈癌组Adler分级明显高于对照组;且绘制ROC曲线证实,Adler分级对宫颈癌具有较高诊断价值。作为实体恶性肿瘤,宫颈癌的生长依赖于宫颈附近血管的生成,通过观察宫颈周围新血管生成情况及血流状况能够辅助诊断宫颈病变性质[19]。在彩色多普勒超声图像上,肿瘤组织内部存在的不同形式血流信号与内部丰富的血管网相对应,与肿瘤结构、病理特征有关。杜阳春等[20]研究指出,彩色多普勒超声Adler分级与宫颈癌临床分期、肿块大小、微血管密度等存在明显相关性。本研究结果显示,2~3级组临床分期、微血管密度、PSV、EDV高于0~1级组,病灶最大直径长于0~1级组,RI低于0~1级组;Adler分级与临床分期、微血管密度、病灶最大直径、PSV、EDV呈正相关,与RI呈负相关,即Adler分级越高临床分期、PSV、EDV越高,微血管密度越大,病灶最大直径越长,RI越低,与上述研究结果相似。可见Adler分级能够反映宫颈癌内部微血管密度特征及血流情况,并为临床分期判断提供帮助。宫颈癌细胞分裂生长活跃、增殖速度快与其肿瘤血管的增殖存在密切联系,临床分期较高的宫颈癌患者肿瘤细胞生长旺盛,会显著增加新生血管生成,增长病灶直径,且血管结构无层次、形态不规则,排列杂乱无章,密度不均,在超声多普勒图像上表现为较高血流信号,故而Adler分级较高。肿瘤细胞分化程度决定其侵袭、转移的能力,而微血管形成是肿瘤细胞赖以存活、获取营养、向远处转移的基础条件,实体瘤血流状况与肿瘤各项病理参数存在密切联系。
综上所述,彩超Adler分级技术在宫颈癌患者中具有较高诊断价值,与宫颈癌临床分期、微血管密度、病灶最大直径等病理指标密切相关,对宫颈癌的诊治具有重要指导意义。
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[1] 徐文飞,梅其杰,明春玉,等. 基于单细胞转录组测序分析骨关节炎软骨细胞分化的分子机制[J]. 生物骨科材料与临床研究,2024,21(1):1-6+13. doi: 10.3969/j.issn.1672-5972.2024.01.001 [2] Guilak F. Biomechanical factors in osteoarthritis[J]. Best Practice & Research Clinical Rheumatology,2011,25(6):815-823. [3] Tong L,Yu H,Huang X,et al. Current understanding of osteoarthritis pathogenesis and relevant new approaches[J]. Bone Research,2022,10(1):60. doi: 10.1038/s41413-022-00226-9 [4] Bai J,Zhang Y,Zheng X,et al. LncRNA MM2P-induced,exosome-mediated transfer of Sox9 from monocyte-derived cells modulates primary chondrocytes[J]. Cell Death & Disease,2020,11(9):763. [5] Hoolwerff M,Metselaar P I,Tuerlings M,et al. Elucidating epigenetic regulation by identifying functional cis-acting long noncoding RNAs and their targets in osteoarthritic articular cartilage[J]. Arthritis & Rheumatology,2020,72(11):1845-1854. [6] Okuyan H M,Begen M A. LncRNAs in osteoarthritis[J]. Clinica Chimica Acta,2022,532:145-163. doi: 10.1016/j.cca.2022.05.030 [7] The ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project[J]. Nature,2007,447(7146):799-816. doi: 10.1038/nature05874 [8] Della Bella E,Koch J,Baerenfaller K. Translation and emerging functions of non-coding RNAs in inflammation and immunity[J]. Allergy,2022,77(7):2025-2037. doi: 10.1111/all.15234 [9] Guo C J,Ma X K,Xing Y H,et al. Distinct Processing of lncRNAs contributes to non-conserved functions in stem cells[J]. Cell,2020,181(3): 621-636. e22. [10] Statello L,Guo C J,Chen L L,et al. Gene regulation by long non-coding RNAs and its biological functions[J]. Nature Reviews Molecular Cell Biology,2021,22(2):96-118. doi: 10.1038/s41580-020-00315-9 [11] Gupta S C,Awasthee N,Rai V,et al. Long non-coding RNAs and nuclear factor-κB crosstalk in cancer and other human diseases[J]. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer,2020,1873(1):188316. doi: 10.1016/j.bbcan.2019.188316 [12] Kretz M,Webster D E,Flockhart R J,et al. Suppression of progenitor differentiation requires the long noncoding RNA ANCR[J]. Genes & Development,2012,26(4):338-343. [13] Frankish A,Diekhans M,Ferreira A M,et al. GENCODE reference annotation for the human and mouse genomes[J]. Nucleic Acids Research,2019,47(D1):D766-D773. doi: 10.1093/nar/gky955 [14] Yan L,Liu G,Wu X. The umbilical cord mesenchymal stem cell‐derived exosomal lncRNA H19 improves osteochondral activity through miR‐29b‐3p/FoxO3 axis[J]. Clinical and Translational Medicine,2021,11(1):e255. doi: 10.1002/ctm2.255 [15] Zhang Y,Liu Q,Liao Q. Long noncoding RNA: A dazzling dancer in tumor immune microenvironment[J]. Journal of Experimental & Clinical Cancer Research,2020,39(1):231. [16] Ye X,Wang S,Zhao X,et al. Role of lncRNAs in cis- and trans-regulatory responses to salt in Populus trichocarpa.[J]. The Plant Journal,2022,110(4):978-993. doi: 10.1111/tpj.15714 [17] Wang F,Tang Z,Shao H,et al. Long noncoding RNA HOTTIP cooperates with CCCTC-binding factor to coordinate HOXA gene expression[J]. Biochemical and Biophysical Research Communications,2018,500(4):852-859. doi: 10.1016/j.bbrc.2018.04.173 [18] Ma Z,Li M,Roy S,et al. Chromatin boundary elements organize genomic architecture and developmental gene regulation in Drosophila Hox clusters[J]. World Journal of Biological Chemistry,2016,7(3):223. doi: 10.4331/wjbc.v7.i3.223 [19] Chu C,Quinn J,Chang H Y. Chromatin Isolation by RNA Purification (ChIRP)[J]. Journal of Visualized Experiments,2012,61:3912. [20] Niehrs C,Luke B. Regulatory R-loops as facilitators of gene expression and genome stability[J]. Nature Reviews Molecular Cell Biology,2020,21(3):167-178. doi: 10.1038/s41580-019-0206-3 [21] Pan H,Wang H,Zhang X,et al. Chromosomal instability-associated MAT1 lncRNA insulates MLL1-guided histone methylation and accelerates tumorigenesis[J]. Cell Reports,2022,41(11):111829. doi: 10.1016/j.celrep.2022.111829 [22] Ghafouri-Fard S,Abak A,Fattahi F,et al. The interaction between miRNAs/lncRNAs and nuclear factor-κB (NF-κB) in human disorders[J]. Biomedicine & Pharmacotherapy,2021,138:111519. [23] Herman A B,Tsitsipatis D,Gorospe M. Integrated lncRNA function upon genomic and epigenomic regulation[J]. Molecular Cell,2022,82(12):2252-2266. doi: 10.1016/j.molcel.2022.05.027 [24] Schmidt K,Weidmann C A,Hilimire T A,et al. Targeting the oncogenic long non-coding RNA SLNCR1 by blocking its sequence-specific binding to the androgen receptor[J]. Cell Reports,2020,30(2): 541-554. e5. [25] Carlevaro-Fita J,Johnson R. Global positioning system: Understanding long noncoding RNAs through subcellular localization[J]. Molecular Cell,2019,73(5):869-883. doi: 10.1016/j.molcel.2019.02.008 [26] Aznaourova M,Janga H,Sefried S,et al. Noncoding RNA MaIL1 is an integral component of the TLR4–TRIF pathway[J]. Proceedings of the National Academy of Sciences,2020,117(16):9042-9053. doi: 10.1073/pnas.1920393117 [27] Gong C,Maquat L E. lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements[J]. Nature,2011,470(7333):284-288. doi: 10.1038/nature09701 [28] 王为,汤翔宇,易智谦,等. 骨关节炎诱导软骨细胞凋亡和细胞外基质降解的机制[J]. 中国组织工程研究,2022,26(20):3133-3140. doi: 10.12307/2022.610 [29] Yang Q,Guo J,Ren Z,et al. LncRNA NONHSAT030515 promotes the chondrogenic differentiation of human adipose-derived stem cells via regulating the miR-490-5p/BMPR2 axis[J]. Journal of Orthopaedic Surgery and Research,2021,16(1):658. doi: 10.1186/s13018-021-02757-z [30] Shen P,Wang B,Zheng C,et al. LRRC75A-AS1 inhibits chondrogenic differentiation of bmscs via targeting the Mir-140-3p/Wnt/Β-Catenin pathway.[J]. Current Stem Cell Research & Therapy,2023,18(8):1142-1149. [31] Wang W,Ding Y,Xu Y,et al. Comprehensive analysis of long noncoding RNAs and mRNAs expression profiles and functional networks during chondrogenic differentiation of murine ATDC5 cells[J]. Acta Biochimica et Biophysica Sinica,2019,51(8):778-790. doi: 10.1093/abbs/gmz064 [32] Liu F,Song D Y,Huang J,et al. Long non-coding RNA CIR inhibits chondrogenic differentiation of mesenchymal stem cells by epigenetically suppressing ATOH8 via methyltransferase EZH2[J]. Molecular Medicine,2021,27(1):12. doi: 10.1186/s10020-021-00272-9 [33] Li X,Yang Y,Liang L,et al. Effect of XBP1 deficiency in cartilage on the regulatory network of lncRNA/circRNA-miRNA-mRNA[J]. International Journal of Biological Sciences,2022,18:315-330. doi: 10.7150/ijbs.64054 [34] Goldring M B. Articular cartilage degradation in osteoarthritis[J]. HSS Journal,2012,8(1):7-9. doi: 10.1007/s11420-011-9250-z [35] Zhang X,Liu X,Ni X,et al. Long non-coding RNA H19 modulates proliferation and apoptosis in osteoarthritis via regulating miR-106a-5p[J]. Journal of Biosciences,2019,44(6):128. doi: 10.1007/s12038-019-9943-x [36] Yang B,Xu L,Wang S. Regulation of lncRNA-H19/miR-140-5p in cartilage matrix degradation and calcification in osteoarthritis[J]. Annals of Palliative Medicine,2020,9(4):1896-1904. doi: 10.21037/apm-20-929 [37] Zhang C,Wang P,Jiang P,et al. Upregulation of lncRNA HOTAIR contributes to IL-1β-induced MMP overexpression and chondrocytes apoptosis in temporomandibular joint osteoarthritis[J]. Gene,2016,586(2):248-253. doi: 10.1016/j.gene.2016.04.016 [38] Wang J,Luo X,Cai S,et al. Blocking HOTAIR protects human chondrocytes against IL-1β-induced cell apoptosis,ECM degradation,inflammatory response and oxidative stress via regulating miR-222-3p/ADAM10 axis[J]. International Immunopharmacology,2021,98:107903. doi: 10.1016/j.intimp.2021.107903 [39] Wang B,Sun Y,Liu N,et al. LncRNA HOTAIR modulates chondrocyte apoptosis and inflammation in osteoarthritis via regulating miR ‐1277‐5p/ SGTB axis[J]. Wound Repair and Regeneration,2021,29(3):495-504. doi: 10.1111/wrr.12908 [40] Zhang H,Chen C,Cui Y,et al. lnc-SAMD14-4 can regulate expression of the COL1A1 and COL1A2 in human chondrocytes[J]. PeerJ,2019,7:e7491. doi: 10.7717/peerj.7491 [41] Li H,Xie S,Li H,et al. LncRNA MALAT1 mediates proliferation of LPS treated-articular chondrocytes by targeting the miR-146a-PI3K/Akt/mTOR axis[J]. Life Sciences,2020,254:116801. doi: 10.1016/j.lfs.2019.116801 [42] Liu C,Ren S,Zhao S,et al. LncRNA MALAT1/MiR-145 adjusts IL-1β-induced chondrocytes viability and cartilage matrix degradation by regulating ADAMTS5 in human osteoarthritis[J]. Yonsei Medical Journal,2019,60(11):1081. doi: 10.3349/ymj.2019.60.11.1081 [43] Gao S T,Yu Y M,Wan L P,et al. LncRNA GAS5 induces chondrocyte apoptosis by down-regulating miR-137[J]. European Review for Medical and Pharmacological Sciences,2020,24(21):10984-10991. [44] Meng Y,Qiu S,Sun L,et al. Knockdown of exosome‑mediated lnc‑PVT1 alleviates lipopolysaccharide‑induced osteoarthritis progression by mediating the HMGB1/TLR4/NF‑κB pathway via miR‑93‑5p[J]. Molecular Medicine Reports,2020,22(6):5313-5325. doi: 10.3892/mmr.2020.11594 [45] Lu X,Yu Y,Yin F,et al. Knockdown of PVT1 inhibits IL-1β-induced injury in chondrocytes by regulating miR-27b-3p/TRAF3 axis[J]. International Immunopharmacology,2020,79:106052. doi: 10.1016/j.intimp.2019.106052 -

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