Int J Stomatol

Int J Stomatol ›› 2021, Vol. 48 ›› Issue (4): 417-425.doi: 10.7518/gjkq.2021070

• Original Articles • Previous Articles     Next Articles

Experimental study on behavior changes of condylar chondrocytes in early stage of temporomandibular joint degeneration

Fang Lingli(),Tan Xi,Ye Yusi,Huang Lan,He Yao()   

  1. Stomatological Hospital of Chongqing Medical University & Chongqing Key Laboratory of Oral Diseases and Biomedical Science & Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China
  • Received:2021-01-11 Revised:2021-04-06 Online:2021-07-01 Published:2021-06-30
  • Contact: Yao He E-mail:2018110874@stu.cqmu.edu.cn;yaohe@hospital.cqmu.edu.cn
  • Supported by:
    National Natural Science Foundation of China(31800786);General projects of China Postdoctoral fund(2018M640902)

RichHTML

20

PDF (PC)

344

Abstract:

Objective To explore the biological behavioural changes in the proliferation, apoptosis and autophagy of condylar chondrocytes and changes in the related signal pathway in the early stage of cartilage degeneration under stress.Methods The forced mouth opening model was used, and samples were taken after 0 d (control group) and 10 d (experiment group) of inducing overloading force. After the laser confocal scanning of the condylar cartilage, 5-ethynyl-2’-deoxyuridine (EdU) staining was performed to detect cell proliferation. The expression of proliferation, apoptosis, autophagy and key proteins of the phosphatidylinositol 3-kinase/ protein kinase B (PI3K/Akt) pathway was detected by haematoxylin/eosin, toluidine blue and immunohistochemical stainings with paraffin sections of the intact temporomandibular joint. Results The thickness of the condylar cartilage increased, but the cell density and cartilage matrix secretion decreased in the experimental group. In addition, the number of proliferation and apoptosis positive cells and the expression of autophagy markers increased. At the same time, the PI3K/Akt pathway was also active. Conclusion The prolife-ration, apoptosis and autophagy activity of chondrocytes were activated to some extent in the early stage of cartilage degeneration induced by stress, with the activation of the PI3K/Akt pathway.

Key words: stress, condyle cartilage, degeneration, autophagy

CLC Number: 

  • R782.6

TrendMD: 

Fig 1

Histomorphology of TMJ cartilage stimulated by stress"

Fig 2

Expression of TMJ cartilage matrix"

Fig 3

Proliferation and apoptosis of TMJ cartilage under stress stimulation"

Fig 4

Expression of autophagy in condylar chondrocytes under stress stimulation"

Fig 5

Expression of p-Akt and p-mTOR in stress-induced TMJ cartilage"

[1] Wang XD, Zhang JN, Gan YH, et al. Current understanding of pathogenesis and treatment of TMJ osteoarthritis[J]. J Dent Res, 2015,94(5):666-673.
doi: 10.1177/0022034515574770
[2] Wieckiewicz M, Boening K, Wiland P, et al. Reported concepts for the treatment modalities and pain m-anagement of temporomandibular disorders[J]. J Headache Pain, 2015,16:106.
doi: 10.1186/s10194-015-0586-5 pmid: 26644030
[3] Ernberg M. The role of molecular pain biomarkers in temporomandibular joint internal derangement[J]. J Oral Rehabil, 2017,44(6):481-491.
doi: 10.1111/joor.12480 pmid: 28054366
[4] Zhang SP, Teo KYW, Chuah SJ, et al. MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis[J]. Biomaterials, 2019,200:35-47.
doi: 10.1016/j.biomaterials.2019.02.006
[5] Kurio N, Saunders C, Bechtold TE, et al. Roles of Ihh signaling in chondroprogenitor function in postnatal condylar cartilage[J]. Matrix Biol, 2018,67:15-31.
doi: 10.1016/j.matbio.2018.02.011
[6] Koyama E, Saunders C, Salhab I, et al. Lubricin is required for the structural integrity and post-natal maintenance of TM[J]. J Dent Res, 2014,93(7):663-670.
doi: 10.1177/0022034514535807
[7] Sperry MM, Yu YH, Kartha S, et al. Intra-articular etanercept attenuates pain and hypoxia from TMJ loading in the rat[J]. J Orthop Res, 2020,38(6):1316-1326.
doi: 10.1002/jor.v38.6
[8] Tanaka E, Detamore MS, Mercuri LG. Degenerative disorders of the temporomandibular joint: etiology, diagnosis, and treatment[J]. J Dent Res, 2008,87(4):296-307.
pmid: 18362309
[9] 康宏. 颞下颌关节的生物力学[J]. 生物医学工程学杂志, 2000,17(3):324-327, 345.
Kang H. Biomechanics of temporomandibular joint[J]. J Biomed Eng, 2000,17(3):324-327, 345.
[10] Tanaka E, Koolstra JH. Biomechanics of the temporomandibular joint[J]. J Dent Res, 2008,87(11):989-991.
doi: 10.1177/154405910808701101
[11] Sobue T, Yeh WC, Chhibber A, et al. Murine TMJ loading causes increased proliferation and chondrocyte maturation[J]. J Dent Res, 2011,90(4):512-516.
doi: 10.1177/0022034510390810
[12] Utreja A, Dyment NA, Yadav S, et al. Cell and matrix response of temporomandibular cartilage to mechanical loading[J]. Osteoarthritis Cartilage, 2016,24(2):335-344.
doi: 10.1016/j.joca.2015.08.010
[13] Tanaka E, Aoyama J, Miyauchi M, et al. Vascular endothelial growth factor plays an important autocrine/paracrine role in the progression of osteoarthritis[J]. Histochem Cell Biol, 2005,123(3):275-281.
pmid: 15856277
[14] Fujisawa T, Kuboki T, Kasai T, et al. A repetitive, steady mouth opening induced an osteoarthritis-like lesion in the rabbit temporomandibular joint[J]. J D-ent Res, 2003,82(9):731-735.
[15] Ou FR, Su K, Sun JD, et al. Temporomandibular joint disorders contribute to anxiety in BalB/C mice[J]. Biochem Biophys Res Commun, 2019,516(2):339-343.
doi: 10.1016/j.bbrc.2019.06.050
[16] Fujita M, Sato-Shigeta M, Mori H, et al. Protective effects of low-intensity pulsed ultrasound on mandibular condylar cartilage exposed to mechanical overloading[J]. Ultrasound Med Biol, 2019,45(4):944-953.
doi: 10.1016/j.ultrasmedbio.2018.12.006
[17] Liu Q, Yang HX, Duan J, et al. Bilateral anterior elevation prosjournal boosts chondrocytes proliferation in mice mandibular condyle[J]. Oral Dis, 2019,25(6):1589-1599.
doi: 10.1111/odi.v25.6
[18] Shen C, Cai GQ, Peng JP, et al. Autophagy protects chondrocytes from glucocorticoids-induced apoptosis via ROS/Akt/FOXO3 signaling[J]. Osteoarthritis Cartilage, 2015,23(12):2279-2287.
doi: 10.1016/j.joca.2015.06.020
[19] Yang HX, Wen Y, Zhang M, et al. MTORC1 coordinates the autophagy and apoptosis signaling in articular chondrocytes in osteoarthritic temporomandibular joint[J]. Autophagy, 2020,16(2):271-288.
doi: 10.1080/15548627.2019.1606647
[20] Chang J, Wang W, Zhang H, et al. The dual role of autophagy in chondrocyte responses in the pathogenesis of articular cartilage degeneration in osteoarth-ritis[J]. Int J Mol Med, 2013,32(6):1311-1318.
doi: 10.3892/ijmm.2013.1520
[21] Zhang M, Zhang J, Lu L, et al. Enhancement of chondrocyte autophagy is an early response in the degenerative cartilage of the temporomandibular joint to biomechanical dental stimulation[J]. Apoptosis, 2013,18(4):423-434.
doi: 10.1007/s10495-013-0811-0 pmid: 23386193
[22] Chen H, Wu GY, Sun Q, et al. Hyperbaric oxygen protects mandibular condylar chondrocytes from interleukin-1β‒induced apoptosis via the PI3K/AKT signaling pathway[J]. Am J Transl Res, 2016,8(11):5108-5117.
[23] Zhang QB, Lai SX, Hou XY, et al. Protective effects of PI3K/Akt signal pathway induced cell autophagy in rat knee joint cartilage injury[J]. Am J Transl Res, 2018,10(3):762-770.
[24] Cravero JD, Carlson CS, Im HJ, et al. Increased expression of the Akt/PKB inhibitor TRB3 in osteoarthritic chondrocytes inhibits insulin-like growth factor 1-mediated cell survival and proteoglycan synjournal[J]. Arthritis Rheum, 2009,60(2):492-500.
doi: 10.1002/art.v60:2
[25] Portal-Núñez S, Esbrit P, Alcaraz MJ, et al. Oxidative stress, autophagy, epigenetic changes and regulation by miRNAs as potential therapeutic targets in osteoarthritis[J]. Biochem Pharmacol, 2016,108:1-10.
[26] He Y, Zhang M, Huang AY, et al. Confocal imaging of mouse mandibular condyle cartilage[J]. Sci Rep, 2017,7:43848.
doi: 10.1038/srep43848
[27] Liu WJ, Luo HY, Wang RL, et al. Rapamycin-induced autophagy promotes the chondrogenic differentiation of synovium-derived mesenchymal stem cells in the temporomandibular joint in response to IL-1β[J]. Biomed Res Int, 2020,2020:4035306.
[28] Jing JJ, Hinton RJ, Mishina Y, et al. Critical role of Bmpr1a in mandibular condyle growth[J]. Connect Tissue Res, 2014,55(Suppl 1):73-78.
doi: 10.3109/03008207.2014.923858
[29] Ogasawara N, Kano F, Hashimoto N, et al. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental temporomandibular joint osteoarthritis[J]. Osteoarthritis Cartilage, 2020,28(6):831-841.
doi: 10.1016/j.joca.2020.03.010
[30] Ma DD, Kou XX, Jin J, et al. Hydrostatic compress force enhances the viability and decreases the apoptosis of condylar chondrocytes through integrin-FAK-ERK/PI3K pathway[J]. Int J Mol Sci, 2016,17(11):E1847.
[31] Grishko V, Xu M, Ho R, et al. Effects of hyaluronic acid on mitochondrial function and mitochondria-driven apoptosis following oxidative stress in human chondrocytes[J]. J Biol Chem, 2009,284(14):9132-9139.
doi: 10.1074/jbc.M804178200
[32] Yan XF, Wu HX, Wu ZY, et al. The new synthetic H2S-releasing SDSS protects MC3T3-E1 osteoblasts against H2O2-induced apoptosis by suppressing oxidative stress, inhibiting MAPKs, and activating the PI3K/akt pathway[J]. Front Pharmacol, 2017,8:7.
[33] Zhang QB, Lai SX, Hou XY, et al. Protective effects of PI3K/Akt signal pathway induced cell autophagy in rat knee joint cartilage injury[J]. Am J Transl Res, 2018,10(3):762-770.
[34] Xiao ZH, Wang JK, Chen SY, et al. Autophagy promotion enhances the protective effect of morroniside on human OA chondrocyte[J]. Biosci Biotechnol Biochem, 2020,84(5):989-996.
doi: 10.1080/09168451.2020.1717925
[35] Cao Y, Klionsky DJ. Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein[J]. Cell Res, 2007,17(10):839-849.
doi: 10.1038/cr.2007.78
[36] Arai A, Kim S, Goldshteyn V, et al. Beclin1 modulates bone homeostasis by regulating osteoclast and chondrocyte differentiation[J]. J Bone Miner Res, 2019,34(9):1753-1766.
doi: 10.1002/jbmr.v34.9
[37] Yang ZM, Tang YX, Lu HD, et al. Long non-coding RNA reprogramming (lncRNA-ROR) regulates cell apoptosis and autophagy in chondrocytes[J]. J Cell Biochem, 2018,119(10):8432-8440.
doi: 10.1002/jcb.v119.10
[38] Shanware NP, Bray K, Abraham RT. The PI3K, metabolic, and autophagy networks: interactive partners in cellular health and disease[J]. Annu Rev Pharmacol Toxicol, 2013,53:89-106.
doi: 10.1146/annurev-pharmtox-010611-134717
[39] Mupparapu M, Oak S, Chang YC, et al. Conventional and functional imaging in the evaluation of temporomandibular joint rheumatoid arthritis: a systematic review[J]. Quintessence Int, 2019,50(9):742-753.
doi: 10.3290/j.qi.a43046 pmid: 31482155
[40] Morales H, Cornelius R. Imaging approach to temporomandibular joint disorders[J]. Clin Neuroradiol, 2016,26(1):5-22.
doi: 10.1007/s00062-015-0465-0 pmid: 26374243
[41] Bianchi J, de Oliveira Ruellas AC, Gonçalves JR, et al. Osteoarthritis of the temporomandibular joint can be diagnosed earlier using biomarkers and machine learning[J]. Sci Rep, 2020,10:8012.
doi: 10.1038/s41598-020-64942-0
[1] Sun Xiaoqian, Zhang Jun. Advances in the effects of mechanical environment on the biological behaviors and mechanism of head and neck cancer [J]. Int J Stomatol, 2023, 50(4): 414-418.
[2] He Jing,Hu Mingjia,Xiao Ning,Li Jia,Sun Wanxin,Ling Lü,Liu Fan. Investigation on the degree of psychological distress and its influencing factors in patients with oral lichen planus [J]. Int J Stomatol, 2023, 50(3): 308-313.
[3] Wang Taiping,Shi Xinglian,Li Zhezhen,Liu Mei,Jiang Jianhong. Analysis of psychological factors and intervention in patients with oral cancer [J]. Int J Stomatol, 2023, 50(2): 203-209.
[4] Ye Yulin,Jiang Liting,Gao Yiming.. Role of autophagy in salivary glands of Sjögren’s syndrome [J]. Int J Stomatol, 2022, 49(5): 556-560.
[5] Li Guiping,Qin Xu,Zhu Guangxun.. Research progress on adenosine monophosphate-activated protein kinase in periodontal disease [J]. Int J Stomatol, 2022, 49(3): 343-348.
[6] Ding Xu,Li Xin,Li Yan,Xia Boyuan,Yu Weixian. Research progress on the relationship among oxidative stress, mitochondrial quality control, and periodontitis [J]. Int J Stomatol, 2021, 48(4): 385-390.
[7] Meng Xiuping,Hou Jianhua,Li Yiran,Sun Mengyao. Research progress on the selection and design of base materials in deep margin elevation [J]. Int J Stomatol, 2021, 48(3): 280-286.
[8] Zhou Feng,Chen Ye,Chen Chen,Zhang Yining,Geng Ruiman,Liu Ji. Mechanism of sirtuin 1 in regulating periodontitis [J]. Int J Stomatol, 2021, 48(3): 341-346.
[9] Li Xin,Li Yan,Ding Xu,Xia Boyuan,Yu Weixian. Role of endoplasmic reticulum stress in periodontitis affecting systemic diseases [J]. Int J Stomatol, 2021, 48(1): 12-17.
[10] Yin Yuanyuan,Ma Huayu,Li Xinyi,Xu Jingchen,Liu Ting,Chen Song,He Shushu. Expression of autophagy related genes in mice periodontal tissue during orthodontic tooth movement [J]. Int J Stomatol, 2020, 47(6): 627-634.
[11] Li Jingya,Shui Yusen,Guo Yongwen. Advances in mechanisms for osteogenic differentiation of human periodontal ligament cells induced by cyclic tensile stress [J]. Int J Stomatol, 2020, 47(6): 652-660.
[12] Zhu Junjin,Zhou Jiaqi,Wu Yingying. Function of autophagy induced by mammalian target of rapamycin complex 1 in bone metabolism [J]. Int J Stomatol, 2020, 47(1): 84-89.
[13] Yan Dan,Zhang Xizhong,Wang Jianguo. 3D finite element analysis for influence of microimplant thread depth on microimplant and mandible [J]. Int J Stomatol, 2019, 46(4): 387-392.
[14] Zhuo Yang,Shengdan Zhang,Chengcheng Liu,Yi Ding. Research progress on salivary markers for diagnosis of aggressive periodontitis [J]. Inter J Stomatol, 2019, 46(1): 55-61.
[15] Donglei Wu,Jing Liu. Research progress on the association between oxidative stress injury and certain oral diseases [J]. Inter J Stomatol, 2019, 46(1): 62-67.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[2] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[3] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[4] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[5] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[7] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[8] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[9] . [J]. Foreign Med Sci: Stomatol, 2004, 31(02): 126 -128 .
[10] . [J]. Inter J Stomatol, 2008, 35(S1): .