title: Role of the mitochondrial pathway in serum deprivation-induced apoptosis of rat endplate cells.
abstract: The apoptosis of cartilage endplates (CEPs), acting as an initiating factor, plays a vital role in the pathogenesis of intervertebral disc degenerative diseases, the underlying molecular mechanism of the apoptotic process in CEPs is still not clear. The present study aimed to investigate the mechanism of CEP cell apoptosis. We found that low levels of fetal bovine serum (FBS) can induce cell apoptosis. Serum deprivation led to high expression levels of caspase-9, caspase-3, PARP, cytochrome-c and Bax. Flow cytometric analysis showed that inhibition of the intrinsic pathway by a caspase-9 inhibitor (z-LEHD-fmk) significantly suppressed serum deprivation-induced apoptosis. However, a caspase-8 inhibitor (z-IETD-fmk) did not reduce apoptotic cell death. These data suggest that serum deprivation induces apoptosis in rat CEP cells via the activation of the intrinsic apoptotic pathway. The efficacy of a caspase-9 inhibitor in attenuating or preventing apoptosis of serum deprivation-induced disc cell apoptosis suggests that targeting the intrinsic apoptotic pathway may be used as a potential therapy for the treatment of disc degeneration.
authors.affiliation: Department of Orthopedic Surgery, Jinshan Hospital, Fudan University, Shanghai, 201508 China. Electronic address: ldf19861101@126.com.
authors.forename: Defang
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Second Affiliated Hospital of Anhui University of Medicine, Hefei, Anhui, 230601, China. Electronic address: zhu290488355@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Orthopedic Surgery, Jinshan Hospital, Fudan University, Shanghai, 201508 China. Electronic address: three_stones2008@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Orthopedic Surgery, Jinshan Hospital, Fudan University, Shanghai, 201508 China. Electronic address: doctor_weilu@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Center Laboratory, Jinshan Hospital, Fudan University, Shanghai, 201508, China. Electronic address: gbobxu@163.com.
authors.forename: Guoxiong
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, Jinshan Hospital, Fudan University, Shanghai, 201508 China. Electronic address: beaccepted@126.com.
authors.forename: Jingping
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D003470:Culture Media / Q000494:pharmacology; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D005333:Fetus; D005786:Gene Expression Regulation; D007403:Intervertebral Disc / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D003470:Culture Media; D009842:Oligopeptides; D051028:bcl-2-Associated X Protein; C403754:benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9
keywords: Apoptosis; Cartilage endplates; Caspase inhibitors; Intervertebral disc degeneration; Mitochondrial pathway; Serum deprivation