Abstract:
PURPOSE:Diabetes mellitus is associated with an increased risk of intervertebral disc degeneration (IDD). Reactive oxygen species (ROS), oxidative stressors, play a key role in autophagy of diabetes-associated diseases. Mitochondria are known to be the main source of endogenous ROS in most mammalian cell types. The authors therefore conducted the following study to evaluate the effects of high glucose concentrations on the induction of oxidative stress and autophagy through mitochondrial damage in rat notochordal cells. METHODS:Rat notochordal cells were isolated, cultured, and placed in either 10% fetal bovine serum (normal control) or 10% fetal bovine serum plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days, respectively. We identified and quantified the mitochondrial damage (mitochondrial transmembrane potential) and the generation of ROS and antioxidants (manganese superoxide dismutase [MnSOD] and catalase). We also investigated expressions and activities of autophagy markers (beclin-1, light chain3-I [LC3-I] and LC3-II, autophagy-related gene [Atg] 3, 5, 7, and 12). RESULTS:An enhanced disruption of mitochondrial transmembrane potential, which indicates mitochondrial damage, was identified in rat notochordal cells treated with both high glucose concentrations. Both high glucose concentrations increased production of ROS by rat notochordal cells in a dose- and time-dependent manner. The two high glucose solutions also enhanced rat notochordal cells' compensatory expressions of MnSOD and catalase in a dose- and time-dependent manner. The proautophagic effects of high glucose concentrations were manifested in the form of enhanced rat notochordal cells' expressions of beclin-1, LC3-II, Atg3, 5, 7, and 12 in a dose- and time-dependent manner. The ratio of LC3-II/LC3-I expression was also increased in a dose- and time-dependent manner. CONCLUSIONS:The findings from this study demonstrate that high glucose-induced oxidative stress promotes autophagy through mitochondrial damage of rat notochordal cells in a dose- and time-dependent manner. These results suggest that preventing the generation of oxidative stress might be a novel therapeutic target by which to prevent or to delay IDD in patients with diabetes mellitus.
journal_name
Int Orthopjournal_title
International orthopaedicsauthors
Park EY,Park JBdoi
10.1007/s00264-013-2037-8subject
Has Abstractpub_date
2013-12-01 00:00:00pages
2507-14issue
12eissn
0341-2695issn
1432-5195journal_volume
37pub_type
杂志文章abstract::Over the last two centuries, treatment of hip pathology has evolved from joint excision and osteotomies to modern total hip arthroplasty (THA), which is considered one of the most successful surgical interventions ever developed. We here review the history of hip procedures that preceded Themistocles Glück. This evalu...
journal_title:International orthopaedics
pub_type: 传,历史文章,杂志文章
doi:10.1007/s00264-013-2004-4
更新日期:2013-11-01 00:00:00
abstract:PURPOSE:Traditionally, valgus knee deformity is predominately corrected by stabilisation with a plate inserted via the medial approach to the supracondylar region of the femur. However, this technique is unfavourable from both a biomechanical and a biological point of view. A revised retrograde dynamic locked nailing w...
journal_title:International orthopaedics
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doi:10.1007/s00264-002-0348-2
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journal_title:International orthopaedics
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doi:10.1007/s00264-008-0573-4
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doi:10.1007/s00264-020-04757-w
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journal_title:International orthopaedics
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doi:10.1007/s00264-007-0369-y
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journal_title:International orthopaedics
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journal_title:International orthopaedics
pub_type: 杂志文章
doi:
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journal_title:International orthopaedics
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journal_title:International orthopaedics
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更新日期:1990-01-01 00:00:00
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journal_title:International orthopaedics
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journal_title:International orthopaedics
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journal_title:International orthopaedics
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更新日期:2015-01-01 00:00:00
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journal_title:International orthopaedics
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journal_title:International orthopaedics
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journal_title:International orthopaedics
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journal_title:International orthopaedics
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更新日期:2002-01-01 00:00:00
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journal_title:International orthopaedics
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更新日期:2018-09-01 00:00:00