Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant

Song, You‐Qiang; Karasugi, Tatsuki; Cheung, Kenneth M.C.; Chiba, Kazuhiro; Ho, Daniel Wai‐Hung; Miyake, Atsushi; Kao, Patrick Y. P.; Sze, Kit Ling; Yee, Anita; Takahashi, Atsushi; Kawaguchi, Yoshiharu; Matsumura, Yasuo; Matsumoto, Morio; Togawa, Daisuke; Kanayama, Masahiro; Shi, Dongquan; Dai, Jin; Jiang, Qing; Wu, Chengai; Tian, Wei; Wang, Na; Leong, J. C. Y.; Luk, Keith D. K.; Yip, Shea Ping; Cherny, Stacey S.; Wang, Junwen; Mundlos, Stefan; Kelempisioti, Anthi; Eskola, Pasi J.; Männikkö, Minna; Mäkelä, P.; Karppinen, Jaro; Järvelin, Marjo‐Riitta; O’Reilly, Paul F.; Kubo, Michiaki; Kimura, Takeshi; Kubo, Toshikazu; Toyama, Yoshiaki; Mizuta, Hiroshi; Cheah, Kathryn S.E.; Tsunoda, Tatsuhiko; Sham, Pak-Chung; Ikegawa, Shiro; Chan, Danny

doi:10.1172/jci69277

Cited by 113 publications

(87 citation statements)

References 51 publications

(51 reference statements)

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“…Carbohydrate sulfotransferase 3 89) Carbohydrate sulfotransferase 3 (CHST3) is an enzyme that catalyzes proteoglycan sulfation. We identified CHST3 as a susceptibility gene for LDDs, using 32,642 subjects consisting of 4,043 LDDs and 28,599 controls from Southern Chinese, Japanese, and Finnish populations 89) .…”

Section: Matrix Metalloproteinase-3 and Other Mmpsmentioning

confidence: 99%

“…We identified CHST3 as a susceptibility gene for LDDs, using 32,642 subjects consisting of 4,043 LDDs and 28,599 controls from Southern Chinese, Japanese, and Finnish populations 89) . This study showed that Rs4148941 was the main locus by a genomewide association study (GWAS).…”

Section: Matrix Metalloproteinase-3 and Other Mmpsmentioning

confidence: 99%

“…The larger sample sizes give more accurate results. Only one paper included over 30,000 samples 89) . The samples from only one race is not sufficient for universal knowledge.…”

Section: Problematic Issues Related To Genetic Research Regarding Lddsmentioning

confidence: 99%

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Genetic background of degenerative disc disease in the lumbar spine

Kawaguchi

2018

Spine Surg Relat Res

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Abstract:This is a review paper on the topic of genetic background of degenerative disc diseases in the lumbar spine. Lumbar disc diseases (LDDs), such as lumbar disc degeneration and lumbar disc herniation, are the main cause of low back pain. There are a lot of studies that tried to identify the causes of LDDs. The causes have been categorized into environmental factors and genetic factors. Recent studies revealed that LDDs are mainly caused by genetic factors. Numerous studies have been carried out using the genetic approach for LDDs. The history of these studies is divided into three periods: (1) era of epidemiological research using familial background and twins, (2) era of genomic research using DNA polymorphisms to identify susceptible genes for LDDs, and (3) era of functional research to determine how the genes cause LDDs. This review article was undertaken to present the history of genetic approach to LDDs and to discuss the current issues and future perspectives.

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Section: Matrix Metalloproteinase-3 and Other Mmpsmentioning

confidence: 99%

Section: Matrix Metalloproteinase-3 and Other Mmpsmentioning

confidence: 99%

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Genetic background of degenerative disc disease in the lumbar spine

Kawaguchi

2018

Spine Surg Relat Res

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“…Human NP cells were seeded into a 24-well dish at a density of 1.5x10 5 cells/well, to a final volume of the culture solution of 250 µl. NP cells were transfected at a multiplicity of infection (MOI) of 10, incubated at 37˚C for 5 h and allowed to recover in fresh culture medium for 96 h at 37˚C with 5% CO 2 (Fig. 1).…”

Section: Reverse Transcription-quantitative Polymerase Chain Reactionmentioning

confidence: 99%

“…IDD manifests as a loss of proteoglycan and water content in the nucleus pulposus (NP) cells of intervertebral discs (2). A previous study has demonstrated that young men are more likely to suffer from IDD than young women (3).…”

Section: Introductionmentioning

confidence: 99%

Role of microRNA-210 in human intervertebral disc degeneration

Zhang

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to investigate the role of microRNA (miR)-210 in the development of intervertebral disc degeneration (IDD). Human nucleus pulposus (NP) samples were collected from patients with scoliosis and IDD (n=12 each) as the scoliosis control and IDD groups, respectively. The expression levels of miR-210 were detected using reverse-transcription quantitative polymerase chain reaction. In vitro overexpression and knockdown of miR-210 in human NP cells were achieved by transfection of NP cells with lentiviral pre-miR-210 and antagomiR-210, respectively. The protein expression levels of homeobox A9 (HOXA9) were then detected in NP cells with modulated miR-210 using western blot analysis. Flow cytometry with allophycocyanin-Annexin V/7 and 7-aminoactinomycin D staining was also used to detect the proportion of NP cells with modulated miR-210 undergoing apoptosis. The current study revealed that the miR-210 expression was decreased in patients with IDD compared with that of the scoliosis control group (P<0.05). Furthermore, the upregulation of miR-210 with pre-miR-210 led to the repression of HOXA9. The HOXA9 level was significantly lower in these cells compared with that of NP cells treated with a corresponding negative sequence (P<0.05). Knockdown of miR-210 with antagomiR-210 resulted in upregulation of HOXA9 in NP cells, determined as the level of HOXA9 was significantly higher than that of NP cells treated with a negative sequence (P<0.05). The proportion of apoptotic NP cells also significantly decreased following treatment with pre-miR-210 compared with the scoliosis control group (12.1±1.43 vs. 23.8±1.22%, respectively; P<0.05). In conclusion, downregulation of miR-210 may promote Fas-mediated apoptosis in human IDD by regulating the expression of HOXA9. This indicates that miR-210 may be closely associated with the development of IDD and may act as a novel target in IDD treatment.

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Aucubin inhibits IL‐1β‐ or TNF‐α‐induced extracellular matrix degradation in nucleus pulposus cell through blocking the miR‐140‐5p/CREB1 axis

Yang

Zhu

et al. 2019

Journal Cellular Physiology

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In intervertebral disc degeneration (IDD), increased proinflammatory molecules secreted by human nucleus pulposus cells (HNPCs) could promote the expression of extracellular matrix (ECM)‐degrading enzymes. IDD could be affected by both genetic and environmental factors, including microRNAs (miRNAs). Aucubin, the active ingredient of a traditional Chinese medicine herb Du Zhong, has been reported to promote osteogenic differentiation; however, the role of aucubin in IDD and the underlying mechanism remain unclear. Herein, we evaluated the effect of aucubin on TNF‐α‐ or IL‐1β‐induced ECM degradation in HNPCs. By using online tools, miR‐140 was selected as a candidate miRNA that is related to TNF‐α or IL‐1β signaling. Overexpression of miR‐140 enhanced the effect of aucubin on ECM degradation. Moreover, cAMP responsive element binding protein 1 (CREB1), a major transcriptional factor in immune‐related signaling, was a direct downstream target of miR‐140. CREB1 knockdown mimicked the function of miR‐140 overexpression on ECM degradation. In summary, aucubin might ameliorate IL‐1β‐ or TNF‐α‐induced ECM degradation in HNPCs through regulating miR‐140/CREB1.

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Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant

Cited by 113 publications

References 51 publications

Genetic background of degenerative disc disease in the lumbar spine

Genetic background of degenerative disc disease in the lumbar spine

Role of microRNA-210 in human intervertebral disc degeneration

Aucubin inhibits IL‐1β‐ or TNF‐α‐induced extracellular matrix degradation in nucleus pulposus cell through blocking the miR‐140‐5p/CREB1 axis

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