title: Static mechanical stress induces apoptosis in rat endplate chondrocytes through MAPK and mitochondria-dependent caspase activation signaling pathways.
abstract: Mechanical stress has detrimental effects on cartilaginous endplate chondrocytes due to apoptosis in vivo and in vitro. In this study, we investigated the possible apoptosis signaling pathways induced by mechanical stress in cultured rat cervical endplate chondrocytes. Static mechanical load significantly reduced cell viability in a time- and load-dependent manner, as demonstrated by the Cell Counting Kit-8 (CCK-8) assay. Chondrocyte apoptosis induced by mechanical stress was confirmed by annexin V/propidium iodide (PI) staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Western blot analysis revealed that static load-induced chondrocyte apoptosis was accompanied by increased phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (MAPK). The loss of mitochondrial membrane potential (ΔΨm), increased Cytochrome c release, and activated Caspase-9 and Caspase-3, indicating that the mitochondrial pathway is involved in mechanical stress-induced chondrocyte apoptosis. Treatment with inhibitors of JNK (SP600125), p38 MAPK (SB203580), and ERK (PD98059) prior to mechanical stimulation reversed both the static load-induced chondrocyte apoptosis and the activation of JNK, p38 MAPK, and ERK. Taken together, the data presented in this study demonstrate that mechanical stress induces apoptosis in rat cervical endplate chondrocytes through the MAPK-mediated mitochondrial apoptotic pathway.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Dechao
authors.initials: D
authors.lastname: Kong
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Zheng
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Daode
authors.initials: D
authors.lastname: Wang
authors.forename: Shihao
authors.initials: S
authors.lastname: Du
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Jiahu
authors.initials: J
authors.lastname: Fang
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival; D019902:Chondrocytes / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013314:Stress, Mechanical
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases
references.citation: Spine (Phila Pa 1976). 2003 Jul 15;28(14):1528-33
references.pmid: 12865839
references.citation: J Clin Invest. 1996 Nov 15;98(10):2425-30
references.pmid: 8941662
references.citation: Apoptosis. 2008 Dec;13(12):1450-64
references.pmid: 18987975
references.citation: Spine (Phila Pa 1976). 2000 Jun 15;25(12):1477-83
references.pmid: 10851095
references.citation: Spine (Phila Pa 1976). 2001 Nov 15;26(22):2414-20
references.pmid: 11707702
references.citation: Curr Opin Cell Biol. 2009 Dec;21(6):871-7
references.pmid: 19822411
references.citation: Nature. 2001 Mar 1;410(6824):37-40
references.pmid: 11242034
references.citation: Science. 2004 Jul 30;305(5684):626-9
references.pmid: 15286356
references.citation: PLoS One. 2011 Mar 08;6(3):e16781
references.pmid: 21408143
references.citation: Nature. 2000 Oct 12;407(6805):789-95
references.pmid: 11048730
references.citation: Curr Opin Cell Biol. 2005 Dec;17(6):617-25
references.pmid: 16243507
references.citation: Oncogene. 1999 Dec 16;18(54):7719-30
references.pmid: 10618712
references.citation: J Cell Biol. 2000 Jul 24;150(2):335-47
references.pmid: 10908576
references.citation: FEBS Lett. 2010 Aug 4;584(15):3305-10
references.pmid: 20621101
references.citation: Toxicol Appl Pharmacol. 2005 Mar 1;203(2):124-31
references.pmid: 15710173
references.citation: Biochim Biophys Acta. 2006 Sep-Oct;1757(9-10):1301-11
references.pmid: 16836974
references.citation: Genes Dev. 2001 Nov 15;15(22):2922-33
references.pmid: 11711427
references.citation: J Biol Chem. 2004 May 21;279(21):22399-403
references.pmid: 15004016
references.citation: Biochem Biophys Res Commun. 2003 May 9;304(3):437-44
references.pmid: 12729577
references.citation: J Cell Physiol. 2004 Feb;198(2):209-22
references.pmid: 14603523
references.citation: J Orthop Res. 2008 Jul;26(7):1018-26
references.pmid: 18306405
references.citation: Cell. 1997 Nov 14;91(4):479-89
references.pmid: 9390557
references.citation: J Biol Chem. 2003 Dec 19;278(51):50940-8
references.pmid: 12952976
references.citation: J Biol Chem. 2003 Sep 19;278(38):36563-71
references.pmid: 12853454
references.citation: Int J Biochem Cell Biol. 2008;40(12):2707-19
references.pmid: 18562239
references.citation: Adv Immunol. 1999;71:163-210
references.pmid: 9917913
references.citation: Science. 2002 Dec 6;298(5600):1911-2
references.pmid: 12471242
references.citation: Osteoarthritis Cartilage. 2004 Jan;12(1):1-16
references.pmid: 14697678
references.citation: Matrix. 1991 Dec;11(6):388-94
references.pmid: 1787831
references.citation: Osteoarthritis Cartilage. 2002 Jan;10(1):71-81
references.pmid: 11795985
references.citation: Osteoarthritis Cartilage. 2001 May;9(4):294-9
references.pmid: 11399092
references.citation: Genes Dev. 2008 Jun 15;22(12):1577-90
references.pmid: 18559474
references.citation: Cell. 1995 Jan 27;80(2):179-85
references.pmid: 7834738
references.citation: Science. 1995 Nov 24;270(5240):1326-31
references.pmid: 7481820
references.citation: Toxicology. 2013 Jan 7;303:72-82
references.pmid: 23103613
references.citation: Bone. 2007 Jun;40(6):1536-43
references.pmid: 17392049
references.citation: Osteoarthritis Cartilage. 2006 Jul;14(7):660-9
references.pmid: 16492401
references.citation: Am J Physiol. 1999 Sep;277(3):L589-95
references.pmid: 10484467
references.citation: Spine (Phila Pa 1976). 1998 Dec 1;23(23):2493-506
references.pmid: 9854748
references.citation: Osteoarthritis Cartilage. 2007 Aug;15(8):884-93
references.pmid: 17408985
references.citation: J Biomed Res. 2012 Mar;26(2):103-9
references.pmid: 23554738
references.citation: J Biol Chem. 1996 Oct 4;271(40):24313-6
references.pmid: 8798679
references.citation: Cell Death Differ. 2000 Jan;7(1):102-11
references.pmid: 10713725
references.citation: J Cell Sci. 2009 Aug 15;122(Pt 16):2801-8
references.pmid: 19795525