p53调控骨关节炎软骨细胞凋亡
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摘要
肿瘤抑制蛋白p53是一种可以有效调节哺乳动物细胞生长的核磷酸化蛋白质。p53表达增加能够激活一系列细胞基因,通过抑制多个细胞周期蛋白依赖性激酶导致细胞周期停滞并凋亡。有研究表明,骨关节炎(osteoarthritis,OA)软骨细胞中,p53的表达高于正常软骨细胞,通过下调p53表达能够减少软骨细胞凋亡,进而预防和缓解骨关节炎病变,这可能与线粒体凋亡途径密切相关,但是具体机制尚不明确。本文通过综述近年来p53调控骨关节炎软骨细胞凋亡的文献资料,为骨关节炎机制和治疗有关研究提供理论基础。
The tumor suppressor protein p53 is a nuclear phosphoprotein that potently regulates the growth of mammalian cells. The increased expression of p53 activates a series of genes, resulting in cell cycle arrest and apoptosis by inhibiting multiple cyclin-dependent kinases. Some studies have shown that the expression of p53 in chondrocytes of osteoarthritis(OA) is higher than that in normal chondrocytes. Down-regulation of p53 expression reduces the apoptosis of chondrocytes and prevent and alleviate OA lesions, which may be closely related to mitochondrial apoptosis pathways, but the specific mechanism remains unclear. This article reviews the literature about p53-regulated chondrocyte apoptosis in OA in recent years, and provides a further basis for OA pathogenesis and treatment research.
The tumor suppressor protein p53 is a nuclear phosphoprotein that potently regulates the growth of mammalian cells. The increased expression of p53 activates a series of genes, resulting in cell cycle arrest and apoptosis by inhibiting multiple cyclin-dependent kinases. Some studies have shown that the expression of p53 in chondrocytes of osteoarthritis(OA) is higher than that in normal chondrocytes. Down-regulation of p53 expression reduces the apoptosis of chondrocytes and prevent and alleviate OA lesions, which may be closely related to mitochondrial apoptosis pathways, but the specific mechanism remains unclear. This article reviews the literature about p53-regulated chondrocyte apoptosis in OA in recent years, and provides a further basis for OA pathogenesis and treatment research.
引文
[1] Park SJ, Jung NJ, Na SS. The effects of exercise on the GAP-43 expression in the spinal cord of arthritis-induced rats [J]. J Phys Ther Sci, 2016, 28(10): 2921-2923
[2] Yu J, Liang F, Huang H, et al. Effects of loading on chondrocyte hypoxia, HIF-1alpha and VEGF in the mandibular condylar cartilage of young rats [J]. Orthod Craniofac Res, 2018, 21(1): 41-47
[3] Peeler J, Ripat J. The effect of low-load exercise on joint pain, function, and activities of daily living in patients with knee osteoarthritis [J]. Knee, 2018, 25(1): 135-145
[4] Li Z, Shen J, Chen Y, et al. Mitochondrial genome sequencing of chondrocytes in osteoarthritis by human mitochondria RT2 ProfilerTM PCR array [J]. Mol Med Rep, 2012, 6(1): 39-44
[5] Sun HB. Mechanical loading, cartilage degradation, and arthritis [J]. Ann N Y Acad Sci, 2010, 1211: 37-50
[6] Komori T. Cell death in chondrocytes, osteoblasts, and osteocytes [J]. Int J Mol Sci, 2016, 17(12). pii: E2045
[7] Zahoor T, Mitchell R, Bhasin P, et al. Effect of low-intensity pulsed ultrasound on joint injury and post-traumatic osteoarthritis: an animal study [J]. Ultrasound Med Biol, 2018, 44(1): 234-242
[8] Li J, Lu D, Dou H, et al. Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the p53 pathway [J]. Nat Commun, 2018, 9(1): 143
[9] Lin M, Lin Y, Li X, et al. Warm sparse-dense wave inhibits cartilage degradation in papain-induced osteoarthritis through the mitogen-activated protein kinase signaling pathway [J]. Exp Ther Med, 2017, 14(4): 3674-3680
[10] Kazantseva M, Eiholzer RA, Mehta S, et al. Elevation of the TP53 isoform Delta133p53beta in glioblastomas: an alternative to mutant p53 in promoting tumour development [J]. J Pathol, 2018, 246(1): 77-88
[11] Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells [J]. Nature, 1979, 278(5701): 261-263
[12] Eliyahu D, Michalovitz D, Eliyahu S, et al. Wild-type p53 can inhibit oncogene-mediated focus formation [J]. Proc Natl Acad Sci U S A, 1989, 86(22): 8763-8767
[13] Wang H, Wang Z, Chen J, et al. Apoptosis induced by NO via phosphorylation of p38 MAPK that stimulates NF-kappaB, p53 and caspase-3 activation in rabbit articular chondrocytes [J]. Cell Biol Int, 2007, 31(9): 1027-1035
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[16] Ashraf S, Cha BH, Kim JS, et al. Regulation of senescence associated signaling mechanisms in chondrocytes for cartilage tissue regeneration [J]. Osteoarthritis Cartilage, 2016, 24(2): 196-205
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[18] Zhang XH, Xu XX, Xu T. Ginsenoside Ro suppresses interleukin-1β-induced apoptosis and inflammation in rat chondrocytes by inhibiting NF-κB [J]. Chin J Nat Med, 2015, 13(4): 283-289
[19] Qiu L, Luo Y, Chen X. Quercetin attenuates mitochondrial dysfunction and biogenesis via upregulated AMPK/SIRT1 signaling pathway in OA rats [J]. Biomed Pharmacother, 2018, 103: 1585-1591
[20] Zan PF, Yao J, Wu Z, et al. Cyclin D1 gene silencing promotes IL-1β-induced apoptosis in rat chondrocytes [J]. J Cell Biochem, 2018, 119(1): 290-299
[21] Nakagawa S, Arai Y, Mazda O, et al. N-acetylcysteine prevents nitric oxide-induced chondrocyte apoptosis and cartilage degeneration in an experimental model of osteoarthritis [J]. J Orthop Res, 2010, 28(2): 156-163
[22] Lee YJ, Kim SA, Lee SH. Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro by inhibiting the p53-dependent mitochondrial apoptotic pathway [J]. Acta Pharmacol Sin, 2016, 37(5): 664-673
[23] Kawakita K, Nishiyama T, Fujishiro T, et al. Akt phosphorylation in human chondrocytes is regulated by p53R2 in response to mechanical stress [J]. Osteoarthritis Cartilage, 2012, 20(12): 1603-1609
[24] Jin S, Levine AJ. The p53 functional circuit [J]. J Cell Sci, 2001, 114(Pt 23): 4139-4140
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[26] Holmvall K, Camper L, Johansson S, et al. Chondrocyte and chondrosarcoma cell integrins with affinity for collagen type II and their response to mechanical stress [J]. Exp Cell Res, 1995, 221(2): 496-503
[27] Agarwal S, Long P, Gassner R, et al. Cyclic tensile strain suppresses catabolic effects of interleukin-1beta in fibrochondrocytes from the temporomandibular joint [J]. Arthritis Rheum, 2001, 44(3): 608-617
[28] Fujisawa T, Hattori T, Takahashi K, et al. Cyclic mechanical stress induces extracellular matrix degradation in cultured chondrocytes via gene expression of matrix metalloproteinases and interleukin-1 [J]. J Biochem, 1999, 125(5): 966-975
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[30] Matsuda K, Yoshida K, Taya Y, et al. p53AIP1 regulates the mitochondrial apoptotic pathway [J]. Cancer Res, 2002, 62(10): 2883-2889
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[33] Feng Z, Zhang H, Levine AJ, et al. The coordinate regulation of the p53 and mTOR pathways in cells [J]. Proc Natl Acad Sci USA, 2005, 102(23): 8204-8209
[34] Hornberger TA, Armstrong DD, Koh TJ, et al. Intracellular signaling specificity in response to uniaxial vs. multiaxial stretch: implications for mechanotransduction [J]. Am J Physiol Cell Physiol, 2005, 288(1): C185-C194
[35] Sugden PH. Ras, Akt, and mechanotransduction in the cardiac myocyte [J]. Circ Res, 2003, 93(12): 1179-1192
[36] Sakamoto K, Aschenbach WG, Hirshman MF, et al. Akt signaling in skeletal muscle: regulation by exercise and passive stretch [J]. Am J Physiol Endocrinol Metab, 2003, 285(5): E1081-E1088
[37] Ravikumar B, Sarkar S, Davies JE, et al. Regulation of mammalian autophagy in physiology and pathophysiology [J]. Physiol Rev, 2010, 90(4): 1383-1435
[38] Vento MT, Zazzu V, Loffreda A, et al. Praf2 is a novel Bcl-xL/Bcl-2 interacting protein with the ability to modulate survival of cancer cells [J]. PLoS One, 2010, 5(12): e15636
[39] Grishko V, Xu M, Wilson G, et al. Apoptosis and mitochondrial dysfunction in human chondrocytes following exposure to lidocaine, bupivacaine, and ropivacaine [J]. J Bone Joint Surg Am, 2010, 92(3): 609-618
[40] Chen JH, Cao JL, Chu YL, et al. T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes [J]. J Zhejiang Univ Sci B, 2008, 9(6): 455-463
[41] Wang W, Zhang Z, Guo Y, et al. Carbon disulfide induces mitochondria-mediated apoptosis in Sertoli-germ cells coculture [J]. Mol Cell Toxicol, 2015, 11(3): 387-388
[42] Martin DA, Elkon KB. Mechanisms of apoptosis [J]. Rheum Dis Clin North Am, 2004, 30(3): 441-454, vii
[43] Kim YS, Li XF, Kang KH, et al. Stigmasterol isolated from marine microalgae Navicula incerta induces apoptosis in human hepatoma HepG2 cells [J]. BMB Rep, 2014, 47(8): 433-438
[44] Wu GJ, Chen TG, Chang HC, et al. Nitric oxide from both exogenous and endogenous sources activates mitochondria-dependent events and induces insults to human chondrocytes [J]. J Cell Biochem, 2007, 101(6): 1520-1531
[45] Cherng YG, Chang HC, Lin YL, et al. Apoptotic insults to human chondrocytes induced by sodium nitroprusside are involved in sequential events, including cytoskeletal remodeling, phosphorylation of mitogen-activated protein kinase kinase kinase-1/c-Jun N-terminal kinase, and Bax-mitochondria-mediated caspase activation [J]. J Orthop Res, 2008, 26(7): 1018-1026
[46] Boronkai A, Bellyei S, Szigeti A, et al. Potentiation of paclitaxel-induced apoptosis by galectin-13 overexpression via activation of Ask-1-p38-MAP kinase and JNK/SAPK pathways and suppression of Akt and ERK1/2 activation in U-937 human macrophage cells [J]. Eur J Cell Biol, 2009, 88(12): 753-763
[47] Rudolf E, Rudolf K, Cervinka M. Selenium activates p53 and p38 pathways and induces caspase-independent cell death in cervical cancer cells [J]. Cell Biol Toxicol, 2008, 24(2): 123-141
[48] Eo SH, Cho H, Kim SJ. Resveratrol inhibits nitric oxide-induced apoptosis via the NF-Kappa B pathway in rabbit articular chondrocytes [J]. Biomol Ther (Seoul), 2013, 21(5): 364-370
[49] Fogarty MP, Downer EJ, Campbell V. A role for c-Jun N-terminal kinase 1 (JNK1), but not JNK2, in the beta-amyloid-mediated stabilization of protein p53 and induction of the apoptotic cascade in cultured cortical neurons [J]. Biochem J, 2003, 371(Pt 3): 789-798
[50] Said TM, Paasch U, Glander HJ, et al. Role of caspases in male infertility [J]. Hum Reprod Update, 2004, 10(1): 39-51
[51] Chen Q, Gao Y, Kao X, et al. SNP-induced apoptosis may be mediated with caspase inhibitor by JNK signaling pathways in rabbit articular chondrocytes [J]. J Toxicol Sci, 2012, 37(1): 157-167
[52] Zhong M, Carney DH, Jo H, et al. Inorganic phosphate induces mammalian growth plate chondrocyte apoptosis in a mitochondrial pathway involving nitric oxide and JNK MAP kinase [J]. Calcif Tissue Int, 2011, 88(2): 96-108
[53] Kim SJ, Hwang SG, Shin DY, et al. p38 kinase regulates nitric oxide-induced apoptosis of articular chondrocytes by accumulating p53 via NFkappa B-dependent transcription and stabilization by serine 15 phosphorylation [J]. J Biol Chem, 2002, 277(36): 33501-33508
[54] Kim SJ, Ju JW, Oh CD, et al. ERK-1/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status [J]. J Biol Chem, 2002, 277(2): 1332-1339
[55] Song Z, Zhang C, He L, et al. Uncovering transcription factor and microRNA risk regulatory pathways associated with osteoarthritis by network analysis [J]. Biochem Biophys Res Commun, 2018, 500(4): 902-906
[56] Li C, Hu Q, Chen Z, et al. MicroRNA-140 suppresses human chondrocytes hypertrophy by targeting SMAD1 and controlling the bone morphogenetic protein pathway in osteoarthritis [J]. Am J Med Sci, 2018, 355(5): 477-487
[57] Guan YJ, Li J, Yang X, et al. Evidence that miR-146a attenuates aging- and trauma-induced osteoarthritis by inhibiting Notch1, IL-6, and IL-1 mediated catabolism [J]. Aging Cell, 2018, 17(3): e12752
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[63] Luo J, Nikolaev AY, Imai S, et al. Negative control of p53 by Sir2alpha promotes cell survival under stress [J]. Cell, 2001, 107(2): 137-148
[64] Vaziri H, Dessain SK, Ng Eaton E, et al. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase [J]. Cell, 2001, 107(2): 149-159
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[68] Takayama K, Ishida K, Matsushita T, et al. SIRT1 regulation of apoptosis of human chondrocytes [J]. Arthritis Rheum, 2009, 60(9): 2731-2740
[69] Matsushita T, Sasaki H, Takayama K, et al. The overexpression of SIRT1 inhibited osteoarthritic gene expression changes induced by interleukin-1β in human chondrocytes [J]. J Orthop Res, 2013, 31(4): 531-537
[70] Fujita N, Matsushita T, Ishida K, et al. Potential involvement of SIRT1 in the pathogenesis of osteoarthritis through the modulation of chondrocyte gene expressions [J]. J Orthop Res, 2011, 29(4): 511-515
[71] Yan S, Wang M, Zhao J, et al. MicroRNA-34a affects chondrocyte apoptosis and proliferation by targeting the SIRT1/p53 signaling pathway during the pathogenesis of osteoarthritis [J]. Int J Mol Med, 2016, 38(1): 201-209
[72] Liu B, Lei M, Hu T, et al. Inhibitory effects of SRT1720 on the apoptosis of rabbit chondrocytes by activating SIRT1 via p53/bax and NF-kappaB/PGC-1alpha pathways [J]. J Huazhong Univ Sci Technolog Med Sci, 2016, 36(3): 350-355
[2] Yu J, Liang F, Huang H, et al. Effects of loading on chondrocyte hypoxia, HIF-1alpha and VEGF in the mandibular condylar cartilage of young rats [J]. Orthod Craniofac Res, 2018, 21(1): 41-47
[3] Peeler J, Ripat J. The effect of low-load exercise on joint pain, function, and activities of daily living in patients with knee osteoarthritis [J]. Knee, 2018, 25(1): 135-145
[4] Li Z, Shen J, Chen Y, et al. Mitochondrial genome sequencing of chondrocytes in osteoarthritis by human mitochondria RT2 ProfilerTM PCR array [J]. Mol Med Rep, 2012, 6(1): 39-44
[5] Sun HB. Mechanical loading, cartilage degradation, and arthritis [J]. Ann N Y Acad Sci, 2010, 1211: 37-50
[6] Komori T. Cell death in chondrocytes, osteoblasts, and osteocytes [J]. Int J Mol Sci, 2016, 17(12). pii: E2045
[7] Zahoor T, Mitchell R, Bhasin P, et al. Effect of low-intensity pulsed ultrasound on joint injury and post-traumatic osteoarthritis: an animal study [J]. Ultrasound Med Biol, 2018, 44(1): 234-242
[8] Li J, Lu D, Dou H, et al. Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the p53 pathway [J]. Nat Commun, 2018, 9(1): 143
[9] Lin M, Lin Y, Li X, et al. Warm sparse-dense wave inhibits cartilage degradation in papain-induced osteoarthritis through the mitogen-activated protein kinase signaling pathway [J]. Exp Ther Med, 2017, 14(4): 3674-3680
[10] Kazantseva M, Eiholzer RA, Mehta S, et al. Elevation of the TP53 isoform Delta133p53beta in glioblastomas: an alternative to mutant p53 in promoting tumour development [J]. J Pathol, 2018, 246(1): 77-88
[11] Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells [J]. Nature, 1979, 278(5701): 261-263
[12] Eliyahu D, Michalovitz D, Eliyahu S, et al. Wild-type p53 can inhibit oncogene-mediated focus formation [J]. Proc Natl Acad Sci U S A, 1989, 86(22): 8763-8767
[13] Wang H, Wang Z, Chen J, et al. Apoptosis induced by NO via phosphorylation of p38 MAPK that stimulates NF-kappaB, p53 and caspase-3 activation in rabbit articular chondrocytes [J]. Cell Biol Int, 2007, 31(9): 1027-1035
[14] Labuschagne CF, Zani F, Vousden KH. Control of metabolism by p53-cancer and beyond [J]. Biochim Biophys Acta Rev Cancer, 2018, 1870(1): 32-42
[15] Song W, Zhang Y, Wang J, et al. Antagonism of cysteinyl leukotriene receptor 1 (cysLTR1) by montelukast suppresses cell senescence of chondrocytes [J]. Cytokine, 2018, 103: 83-89
[16] Ashraf S, Cha BH, Kim JS, et al. Regulation of senescence associated signaling mechanisms in chondrocytes for cartilage tissue regeneration [J]. Osteoarthritis Cartilage, 2016, 24(2): 196-205
[17] Hashimoto S, Nishiyama T, Hayashi S, et al. Role of p53 in human chondrocyte apoptosis in response to shear strain [J]. Arthritis Rheum, 2009, 60(8): 2340-2349
[18] Zhang XH, Xu XX, Xu T. Ginsenoside Ro suppresses interleukin-1β-induced apoptosis and inflammation in rat chondrocytes by inhibiting NF-κB [J]. Chin J Nat Med, 2015, 13(4): 283-289
[19] Qiu L, Luo Y, Chen X. Quercetin attenuates mitochondrial dysfunction and biogenesis via upregulated AMPK/SIRT1 signaling pathway in OA rats [J]. Biomed Pharmacother, 2018, 103: 1585-1591
[20] Zan PF, Yao J, Wu Z, et al. Cyclin D1 gene silencing promotes IL-1β-induced apoptosis in rat chondrocytes [J]. J Cell Biochem, 2018, 119(1): 290-299
[21] Nakagawa S, Arai Y, Mazda O, et al. N-acetylcysteine prevents nitric oxide-induced chondrocyte apoptosis and cartilage degeneration in an experimental model of osteoarthritis [J]. J Orthop Res, 2010, 28(2): 156-163
[22] Lee YJ, Kim SA, Lee SH. Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro by inhibiting the p53-dependent mitochondrial apoptotic pathway [J]. Acta Pharmacol Sin, 2016, 37(5): 664-673
[23] Kawakita K, Nishiyama T, Fujishiro T, et al. Akt phosphorylation in human chondrocytes is regulated by p53R2 in response to mechanical stress [J]. Osteoarthritis Cartilage, 2012, 20(12): 1603-1609
[24] Jin S, Levine AJ. The p53 functional circuit [J]. J Cell Sci, 2001, 114(Pt 23): 4139-4140
[25] Tanaka H, Arakawa H, Yamaguchi T, et al. A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage [J]. Nature, 2000, 404(6773): 42-49
[26] Holmvall K, Camper L, Johansson S, et al. Chondrocyte and chondrosarcoma cell integrins with affinity for collagen type II and their response to mechanical stress [J]. Exp Cell Res, 1995, 221(2): 496-503
[27] Agarwal S, Long P, Gassner R, et al. Cyclic tensile strain suppresses catabolic effects of interleukin-1beta in fibrochondrocytes from the temporomandibular joint [J]. Arthritis Rheum, 2001, 44(3): 608-617
[28] Fujisawa T, Hattori T, Takahashi K, et al. Cyclic mechanical stress induces extracellular matrix degradation in cultured chondrocytes via gene expression of matrix metalloproteinases and interleukin-1 [J]. J Biochem, 1999, 125(5): 966-975
[29] Oda K, Arakawa H, Tanaka T, et al. p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53[J].Cell,2000,102(6): 849-862
[30] Matsuda K, Yoshida K, Taya Y, et al. p53AIP1 regulates the mitochondrial apoptotic pathway [J]. Cancer Res, 2002, 62(10): 2883-2889
[31] Okamura S, Arakawa H, Tanaka T, et al. p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis [J]. Mol Cell, 2001, 8(1): 85-94
[32] Levine AJ, Feng Z, Mak TW, et al. Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways[J]. Genes Dev, 2006, 20(3): 267-275
[33] Feng Z, Zhang H, Levine AJ, et al. The coordinate regulation of the p53 and mTOR pathways in cells [J]. Proc Natl Acad Sci USA, 2005, 102(23): 8204-8209
[34] Hornberger TA, Armstrong DD, Koh TJ, et al. Intracellular signaling specificity in response to uniaxial vs. multiaxial stretch: implications for mechanotransduction [J]. Am J Physiol Cell Physiol, 2005, 288(1): C185-C194
[35] Sugden PH. Ras, Akt, and mechanotransduction in the cardiac myocyte [J]. Circ Res, 2003, 93(12): 1179-1192
[36] Sakamoto K, Aschenbach WG, Hirshman MF, et al. Akt signaling in skeletal muscle: regulation by exercise and passive stretch [J]. Am J Physiol Endocrinol Metab, 2003, 285(5): E1081-E1088
[37] Ravikumar B, Sarkar S, Davies JE, et al. Regulation of mammalian autophagy in physiology and pathophysiology [J]. Physiol Rev, 2010, 90(4): 1383-1435
[38] Vento MT, Zazzu V, Loffreda A, et al. Praf2 is a novel Bcl-xL/Bcl-2 interacting protein with the ability to modulate survival of cancer cells [J]. PLoS One, 2010, 5(12): e15636
[39] Grishko V, Xu M, Wilson G, et al. Apoptosis and mitochondrial dysfunction in human chondrocytes following exposure to lidocaine, bupivacaine, and ropivacaine [J]. J Bone Joint Surg Am, 2010, 92(3): 609-618
[40] Chen JH, Cao JL, Chu YL, et al. T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes [J]. J Zhejiang Univ Sci B, 2008, 9(6): 455-463
[41] Wang W, Zhang Z, Guo Y, et al. Carbon disulfide induces mitochondria-mediated apoptosis in Sertoli-germ cells coculture [J]. Mol Cell Toxicol, 2015, 11(3): 387-388
[42] Martin DA, Elkon KB. Mechanisms of apoptosis [J]. Rheum Dis Clin North Am, 2004, 30(3): 441-454, vii
[43] Kim YS, Li XF, Kang KH, et al. Stigmasterol isolated from marine microalgae Navicula incerta induces apoptosis in human hepatoma HepG2 cells [J]. BMB Rep, 2014, 47(8): 433-438
[44] Wu GJ, Chen TG, Chang HC, et al. Nitric oxide from both exogenous and endogenous sources activates mitochondria-dependent events and induces insults to human chondrocytes [J]. J Cell Biochem, 2007, 101(6): 1520-1531
[45] Cherng YG, Chang HC, Lin YL, et al. Apoptotic insults to human chondrocytes induced by sodium nitroprusside are involved in sequential events, including cytoskeletal remodeling, phosphorylation of mitogen-activated protein kinase kinase kinase-1/c-Jun N-terminal kinase, and Bax-mitochondria-mediated caspase activation [J]. J Orthop Res, 2008, 26(7): 1018-1026
[46] Boronkai A, Bellyei S, Szigeti A, et al. Potentiation of paclitaxel-induced apoptosis by galectin-13 overexpression via activation of Ask-1-p38-MAP kinase and JNK/SAPK pathways and suppression of Akt and ERK1/2 activation in U-937 human macrophage cells [J]. Eur J Cell Biol, 2009, 88(12): 753-763
[47] Rudolf E, Rudolf K, Cervinka M. Selenium activates p53 and p38 pathways and induces caspase-independent cell death in cervical cancer cells [J]. Cell Biol Toxicol, 2008, 24(2): 123-141
[48] Eo SH, Cho H, Kim SJ. Resveratrol inhibits nitric oxide-induced apoptosis via the NF-Kappa B pathway in rabbit articular chondrocytes [J]. Biomol Ther (Seoul), 2013, 21(5): 364-370
[49] Fogarty MP, Downer EJ, Campbell V. A role for c-Jun N-terminal kinase 1 (JNK1), but not JNK2, in the beta-amyloid-mediated stabilization of protein p53 and induction of the apoptotic cascade in cultured cortical neurons [J]. Biochem J, 2003, 371(Pt 3): 789-798
[50] Said TM, Paasch U, Glander HJ, et al. Role of caspases in male infertility [J]. Hum Reprod Update, 2004, 10(1): 39-51
[51] Chen Q, Gao Y, Kao X, et al. SNP-induced apoptosis may be mediated with caspase inhibitor by JNK signaling pathways in rabbit articular chondrocytes [J]. J Toxicol Sci, 2012, 37(1): 157-167
[52] Zhong M, Carney DH, Jo H, et al. Inorganic phosphate induces mammalian growth plate chondrocyte apoptosis in a mitochondrial pathway involving nitric oxide and JNK MAP kinase [J]. Calcif Tissue Int, 2011, 88(2): 96-108
[53] Kim SJ, Hwang SG, Shin DY, et al. p38 kinase regulates nitric oxide-induced apoptosis of articular chondrocytes by accumulating p53 via NFkappa B-dependent transcription and stabilization by serine 15 phosphorylation [J]. J Biol Chem, 2002, 277(36): 33501-33508
[54] Kim SJ, Ju JW, Oh CD, et al. ERK-1/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status [J]. J Biol Chem, 2002, 277(2): 1332-1339
[55] Song Z, Zhang C, He L, et al. Uncovering transcription factor and microRNA risk regulatory pathways associated with osteoarthritis by network analysis [J]. Biochem Biophys Res Commun, 2018, 500(4): 902-906
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