Association of Endothelin-1 Expression and Cartilaginous Endplate Degeneration in Humans

Yuan, Wei; Zhao, Mengnan; Yuan, Feng-Lai; Che, Wu; Duan, Ping‐Guo; Liu, Yi; Dong, Jian

doi:10.1371/journal.pone.0060062

Cited by 13 publications

(13 citation statements)

References 38 publications

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“…EDN1 (endothelin 1) gene expression was observed to be enhanced (Additional file 1 ). It has been reported, that overexpression of endothelin 1 is associated with cartilage degeneration [ 28 ]. In contrast to this, the inhibitor of apoptosis, BIRC3 (Additional file 1 ) [ 29 ], was enhanced hinting towards an improved cell survival.…”

Section: Discussionmentioning

confidence: 99%

Differential gene expression of human chondrocytes cultured under short-term altered gravity conditions during parabolic flight maneuvers

et al. 2015

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BackgroundChondrocytes are the main cellular component of articular cartilage. In healthy tissue, they are embedded in a strong but elastic extracelluar matrix providing resistance against mechanical forces and friction for the joints. Osteoarthritic cartilage, however, disrupted by heavy strain, has only very limited potential to heal. One future possibility to replace damaged cartilage might be the scaffold-free growth of chondrocytes in microgravity to form 3D aggregates.ResultsTo prepare for this, we have conducted experiments during the 20th DLR parabolic flight campaign, where we fixed the cells after the first (1P) and the 31st parabola (31P). Furthermore, we subjected chondrocytes to isolated vibration and hypergravity conditions. Microarray and quantitative real time PCR analyses revealed that hypergravity regulated genes connected to cartilage integrity (BMP4, MMP3, MMP10, EDN1, WNT5A, BIRC3). Vibration was clearly detrimental to cartilage (upregulated inflammatory IL6 and IL8, downregulated growth factors EGF, VEGF, FGF17). The viability of the cells was not affected by the parabolic flight, but showed a significantly increased expression of anti-apoptotic genes after 31 parabolas. The IL-6 release of chondrocytes cultured under conditions of vibration was not changed, but hypergravity (1.8 g) induced a clear elevation of IL-6 protein in the supernatant compared with corresponding control samples.ConclusionTaken together, this study provided new insights into the growth behavior of chondrocytes under short-term microgravity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12964-015-0095-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Differential gene expression of human chondrocytes cultured under short-term altered gravity conditions during parabolic flight maneuvers

et al. 2015

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“…Manacu CA et al 14 OA Articular chondrocyte ET-1 caused NO, MMP1 and MMP13 overexpression. Wei Yuan et al 45 Lumbar disc degeneration Cells from endplate ET-1 increased MMP-1 and MMP-13, decreased TIMP-1, and induced NO.…”

Section: Authorsmentioning

confidence: 99%

“…NO mediated such inhibition of ET-1 effects. Very recently, local level of ET-1 was also linked up to the dysfunctional disc cells in the degeneration of lumbar intervertebral disc 45 .…”

Section: Authorsmentioning

confidence: 99%

The emerging role of endothelin-1 in the pathogenesis of subchondral bone disturbance and osteoarthritis

Sin

Tang

Wen

et al. 2015

Osteoarthritis and Cartilage

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Mounting evidence suggests reconceptualizing osteoarthritis (OA) as an inflammatory disorder. Trauma and obesity, the common risk factors of OA, could trigger the local or systemic inflammatory cytokines cascade. Inflammatory bone loss has been well documented; yet it remains largely unknown about the link between the inflammation and hypertrophic changes of subchondral bone seen in OA, such as osteophytosis and sclerosis. Amid a cohort of inflammatory cytokines, endothelin-1 (ET-1) could stimulate the osteoblast-mediated bone formation in both physiological (postnatal growth of trabecular bone) and pathological conditions (bone metastasis of prostate or breast cancer). Also, ET-1 is known as a mitogen and contributes to fibrosis in various organs, e.g., skin, liver, lung, kidney heart and etc., as a result of inflammatory or metabolic disorders. Subchondral bone sclerosis shared the similarity with fibrosis in terms of the overproduction of collagen type I. We postulated that ET-1 might have a hand in the subchondral bone sclerosis of OA. Meanwhile, ET-1 was also able to stimulate the production of matrix metalloproteinase (MMP)-1 and 13 by articular chondrocytes and synoviocytes, by which it might trigger the enzymatic degradation of articular cartilage. Taken together, ET-1 signaling may play a role in destruction of bone-cartilage unit in the pathogenesis of OA; it warrants further investigations to potentiate ET-1 as a novel diagnostic biomarker and therapeutic target for rescue of OA.

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“…Before this study, no comparative and quantitative proteomic analyses of normal and degenerated AF cells had been reported. There has been growing interest in investigating AF cells in patients with IVD degeneration by using enzyme–linked immunosorbent assay, rich Internet application, or luminescence immunoassay to measure the levels of known proteins . However, differential protein expression and its functional consequences in degenerated AF cells are still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…There has been growing interest in investigating AF cells in patients with IVD degeneration by using enzyme-linked immunosorbent assay, rich Internet application, or luminescence immunoassay to measure the levels of known proteins. [11][12][13][14] However, differential protein expression and its functional consequences in degenerated AF cells are still unknown. In the present study, comparative proteomic analysis was used to identify proteins that display altered expression levels in human AF cells.…”

Section: Discussionmentioning

confidence: 99%

Comparative and quantitative proteomic analysis of normal and degenerated human annulus fibrosus cells

Liang

Dai

et al. 2015

Clin Exp Pharma Physio

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Degeneration of the intervertebral disc (IVD) is a major chronic medical condition associated with back pain. To better understand the pathogenesis of IVD degeneration, we performed comparative and quantitative proteomic analyses of normal and degenerated human annulus fibrosus (AF) cells and identified proteins that are differentially expressed between them. Annulus fibrosus cells were isolated and cultured from patients with lumbar disc herniation (the experimental group, degenerated AF cells) and scoliosis patients who underwent orthopaedic surgery (the control group, normal AF cells). Comparative proteomic analyses of normal and degenerated cultured AF cells were carried out using 2-D electrophoresis, mass spectrometric analyses, and database searching. Quantitative analyses of silver-stained 2-D electrophoresis gels of normal and degenerated cultured AF cells identified 10 protein spots that showed the most altered differential expression levels between the two groups. Among these, three proteins were decreased, including heat shock cognate 71-kDa protein, glucose-6-phosphate 1-dehydrogenase, and protocadherin-23, whereas seven proteins were increased, including guanine nucleotide-binding protein G(i) subunit α-2, superoxide dismutase, transmembrane protein 51, adenosine receptor A3, 26S protease regulatory subunit 8, lipid phosphate phosphatase-related protein, and fatty acyl-crotonic acid reductase 1. These differentially expressed proteins might be involved in the pathophysiological process of IVD degeneration and have potential values as biomarkers of the degeneration of IVD.

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Association of Endothelin-1 Expression and Cartilaginous Endplate Degeneration in Humans

Cited by 13 publications

References 38 publications

Differential gene expression of human chondrocytes cultured under short-term altered gravity conditions during parabolic flight maneuvers

Differential gene expression of human chondrocytes cultured under short-term altered gravity conditions during parabolic flight maneuvers

The emerging role of endothelin-1 in the pathogenesis of subchondral bone disturbance and osteoarthritis

Comparative and quantitative proteomic analysis of normal and degenerated human annulus fibrosus cells

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