The Effects of TWEAK, Fn14, and TGF-beta1 on Degeneration of Human Intervertebral Disc.
10.3340/jkns.2010.47.1.30
- Author:
Hoon HUH
1
;
Yong Jik LEE
;
Jung Hee KIM
;
Min Ho KONG
;
Kwan Young SONG
;
Gun CHOI
Author Information
1. Department of Neurosurgery, Medical Institute, Seoul Medical Center, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Intervertebral disc;
TWEAK;
Fn14;
TGF-beta1;
Sox9;
Versican
- MeSH:
Apoptosis;
Fibroblasts;
Glycosaminoglycans;
Humans;
Incubators;
Intervertebral Disc;
Intervertebral Disc Degeneration;
Reverse Transcriptase Polymerase Chain Reaction;
RNA;
RNA, Messenger;
Transforming Growth Factor beta1;
Tumor Necrosis Factor-alpha;
Versicans
- From:Journal of Korean Neurosurgical Society
2010;47(1):30-35
- CountryRepublic of Korea
- Language:English
-
Abstract:
OBJECTIVE: The purpose of this study is to explain the effect and reciprocal action among tumor necrosis factor (TNF) like weak inducer of apoptosis (TWEAK), fibroblast growth factor-inducible 14 (Fn14), and transforming growth factor-beta1 (TGF-beta1) on degeneration of human intervertebral disc (IVD). METHODS: Human intervertebral disc tissues and cells were cultured with Dulbecco's Modified Eagle's Medium/Nutrient F-12 Ham (DMEM/F-12) media in 37degrees C, 5% CO2 incubator. When IVD tissues were cultured with TWEAK, Fn14 that is an antagonistic receptor for TWEAK and TGF-beta1, the level of sulfated glycosaminoglycan (sGAG) was estimated by dimethyl methyleneblue (DMMB) assay and sex determining region Y (SRY)-box 9 (Sox9) and versican messenger ribonucleic acid (mRNA) levels were estimated by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: When human IVD tissue was cultured for nine days, the sGAG content was elevated in proportion to culture duration. The sGAG was decreased significantly by TWEAK 100 ng/mL, however, Fn14 500 ng/mL did not change the sGAG production of IVD tissue. The Fn14 increased versican and Sox9 mRNA levels decreased with TWEAK in IVD tissue TGF-beta1 20 ng/mL elevated the sGAG concentration 40% more than control. The sGAG amount decreased with TWEAK was increased with Fn14 or TGF-beta1 but the result was insignificant statistically. TGF-beta1 increased the Sox9 mRNA expression to 180% compared to control group in IVD tissue. Sox9 and versican mRNA levels decreased by TWEAK were increased with TGF-beta1 in primary cultured IVD cells, however, Fn14 did not show increasing effect on Sox9 and versican. CONCLUSION: This study suggests that TWEAK would act a role in intervertebral disc degeneration through decreasing sGAG and the mRNA level of versican and Sox9.