scholarly journals Type II collagen‐positive embryonic progenitors are the major contributors to spine and intervertebral disc development and repair

Author(s):  
Xinhua Li ◽  
Shuting Yang ◽  
Ling Qin ◽  
Shuying Yang
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhu Guo ◽  
Chensheng Qiu ◽  
Christina Mecca ◽  
Yang Zhang ◽  
Jiang Bian ◽  
...  

Abstract Background Intervertebral disc degeneration (IVDD) is a primary cause of degenerative disc diseases; however, the mechanisms underlying the degeneration remain unclear. The immunoinflammatory response plays an important role in IVDD progression. The inflammatory cytokine lymphotoxin-α (LTα), formerly known as TNFβ, is associated with various pathological conditions, while its role in the pathogenesis of IVDD remains elusive. Methods Real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting (WB), and enzyme-linked immunosorbent assays were used to assess the levels of LTα in human nucleus pulposus (NP) tissues between degeneration and control groups. The plasma concentrations of LTα and C-reactive protein (CRP) were compared between healthy and IVDD patients. Rat primary NP cells were cultured and identified via immunofluorescence. Methyl-thiazolyl-tetrazolium assays and flow cytometry were used to evaluate the effects of LTα on rat NP cell viability. After NP cells were treated with LTα, degeneration-related molecules (Caspase-3, Caspase-1, matrix metalloproteinase (MMP) -3, aggrecan and type II collagen) were measured via RT-qPCR and WB. Results The levels of both the mRNA and protein of LTα in human degenerated NP tissue significantly increased. Plasma LTα and CRP did not differ between healthy controls and IVDD patients. Rat primary NP cells were cultured, and the purity of primary NP cells was > 90%. Cell experiments showed inversely proportional relationships among the LTα dose, treatment time, and cell viability. The optimal conditions (dose and time) for LTα treatment to induce rat NP cell degeneration were 5 μg/ml and 48 ~ 72 h. The apoptosis rate and the levels of Caspase-3, Caspase-1, and MMP-3 significantly increased after LTα treatment, while the levels of type II collagen and aggrecan were decreased, and the protein expression levels were consistent with their mRNA expression levels. Conclusions This study demonstrated that elevated LTα is closely associated with IVDD and that LTα may induce NP cell apoptosis and reduce important extracellular matrix (ECM) proteins, which cause adverse effects on IVDD progress. Moreover, the optimal conditions for LTα treatment to induce NP cell degeneration were determined.


2010 ◽  
Vol 20 ◽  
pp. 134-148 ◽  
Author(s):  
L Calderon ◽  
◽  
E Collin ◽  
D Velasco-Bayon ◽  
M Murphy ◽  
...  

Author(s):  
Joana C. Antunes ◽  
Catarina Leite Pereira ◽  
Graciosa Q. Teixeira ◽  
Ricardo V. Silva ◽  
Joana Caldeira ◽  
...  

2021 ◽  
Author(s):  
Audrey McAlinden ◽  
David M Hudson ◽  
Aysel A Fernandes ◽  
Soumya Ravindran ◽  
Russell J Fernandes

For next generation tissue-engineered constructs and regenerative medicine to succeed clinically, the basic biology and extracellular matrix composition of tissues that these repair techniques seek to restore have to be fully determined. Using the latest reagents coupled with tried and tested methodologies, we continue to uncover previously undetected structural proteins in mature intervertebral disc. In this study we show that the ″embryonic″ type IIA procollagen isoform (containing a cysteine-rich amino propeptide) was biochemically detectable in the annulus fibrosus of both calf and mature steer intervertebral discs, but not in the nucleus pulposus where the type IIB isoform was predominantly localized. Specifically, the triple-helical type IIA procollagen isoform immunolocalized in the outer margins of the inner annulus fibrosus. Triple helical processed type II collagen exclusively localized within the inter- lamellae regions and with type IIA procollagen in the intra-lamellae regions. Mass spectrometry of the a1(II) collagen chains from the region where type IIA procollagen localized showed high 3-hydroxylation of Proline-944, a post- translational modification that is correlated with thin collagen fibrils as in the nucleus pulposus. The findings implicate small diameter fibrils of type IIA procollagen in select regions of the annulus fibrosus where it likely contributes to the organization of collagen bundles and structural properties within the type I- type II collagen transition zone.


JOR Spine ◽  
2019 ◽  
Vol 2 (4) ◽  
Author(s):  
Yulong Wei ◽  
Robert J. Tower ◽  
Zuozhen Tian ◽  
Bhavana Mohanraj ◽  
Robert L. Mauck ◽  
...  

2018 ◽  
Vol 206 (1-2) ◽  
pp. 73-81 ◽  
Author(s):  
Xue Yin ◽  
Silvia  Gonzales ◽  
Somya Sha ◽  
Howard Levene ◽  
Chun-Yuh Huang

Compressive loading promotes adenosine triphosphate (ATP) production and release by intervertebral disc (IVD) cells. Extracellular ATP can be rapidly hydrolyzed by ectonucleotidases. Adenosine, one of the adenine derivatives of ATP hydrolysis, can modulate diverse cellular actions via adenosine receptors. The objectives of this study were to investigate the effects of exogenous adenosine on the production of extracellular matrix (ECM; i.e., collagen type II and aggrecan) and ATP of IVD cells and explore the underlying mechanism of action. It was found that adenosine treatment significantly upregulated aggrecan and type II collagen gene expression and the ATP level in IVD cells. Dipyridamole, an adenosine transport blocker, completely suppressed the effects of adenosine on the ATP production and ECM gene expression of the IVD cells, whereas antagonists of adenosine receptors did not significantly affect adenosine-treated IVD cells. The findings suggested that elevated intracellular ATP and upregulation of ECM gene expression by adenosine treatment are mainly due to adenosine uptake rather than receptor activation. Since ECM biosynthesis is a high ATP demanding process, supplementing adenosine could be beneficial as IVD cells are able to utilize it to replenish intracellular ATP and sequentially promote ECM production, which is constantly suppressed by limited nutrition supply due to the avascular nature of the IVD.


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