Mineralized collagen-modified PMMA cement enhances bone integration and reduces fibrous encapsulation in the treatment of lumbar degenerative disc disease

Abstract As a minimally invasive surgery, percutaneous cement discoplasty (PCD) is now contemplated to treat lumbar disc degeneration disease in elder population. Here, we investigated whether the osteogenic mineralized collagen (MC) modified polymethylmethacrylate (PMMA) cement could be a suitable material in PCD surgery. Injectability, hydrophilicity and mechanical properties of the MC-modified PMMA (PMMA-MC) was characterized. The introduction of MC did not change the application and setting time of PMMA and was easy to be handled in minimally invasive operation. Hydrophilicity of PMMA-MC was greatly improved and its elastic modulus was tailored to complement mechanical performance of bone under dynamic stress. Then, PCD surgery in a goat model with induced disc degeneration was performed with implantation of PMMA-MC or PMMA. Three months after implantation, micro-computed tomography analysis revealed a 36.4% higher circumferential contact index between PMMA-MC and bone, as compared to PMMA alone. Histological staining confirmed that the surface of PMMA-MC was in direct contact with new bone, while the PMMA was covered by fibrous tissue. The observed gathering of macrophages around the implant was suspected to be the cause of fibrous encapsulation. Therefore, the interactions of PMMA and PMMA-MC with macrophages were investigated in vitro. We discovered that the addition of MC could hinder the proliferation and fusion of the macrophages. Moreover, expressions of fibroblast-stimulating growth factors, insulin-like growth factor, basic fibroblast growth factor and tumor necrosis factor-β were significantly down-regulated in the macrophages cocultured with PMMA-MC. Together, the promoted osteointegration and reduced fibrous tissue formation observed with PMMA-MC material makes it a promising candidate for PCD surgery.

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Prevention of lumbar disc degeneration through co-manipulation of insulin-like growth factor 1 and vascular endothelial growth factor

10.21203/rs.3.rs-54211/v1 ◽

2020 ◽

Author(s):

Shan Zhao ◽

Zuo-Zhou Ye ◽

Zuo-qing Liu

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Disc Degeneration ◽

Lumbar Disc ◽

Vascular Endothelial ◽

Insulin Like Growth Factor ◽

Lumbar Disc Degeneration ◽

Gene Therapy Approach ◽

Aged People ◽

Endothelial Growth Factor

Abstract Background: Associated with abnormal angiogenesis and disc dysfunction, Lumbar disc degeneration (LDD) appears to be an important disease suffered by aged people. Previous studies have highlighted the importance of insufficient insulin-like growth factor 1 (IGF1) and excessive vascular endothelial growth factor (VEGF) in the development and progression of LDD, whereas a practical therapeutic strategy is lacking. Results: Here, we did a gene therapy approach using adeno-associated virus (AAV) carrying both IGF1 and shVEGF (AAV-IGF1/shVEGF), which simultaneously corrected IGF1 and VEGF issues in a rat model for LDD.We found that AAV-IGF1/shVEGF significantly reduced disc cell death in the vertebral pulp and annulus fibrosus and significantly improved the lumbar proteoglycan and collagen II levels. Therefore, this approach effectively prevented the development of LDD. Conclusions: Our study presents a novel therapeutic approach on LDD, which is clinically translatable.

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Insulin-Like Growth Factor 1 Activates PI3k/Akt Signaling to Antagonize Lumbar Disc Degeneration

Cellular Physiology and Biochemistry ◽

10.1159/000430347 ◽

2015 ◽

Vol 37 (1) ◽

pp. 225-232 ◽

Cited By ~ 10

Author(s):

Zuoqing Liu ◽

Kaihua Zhou ◽

Wenqin Fu ◽

Hailong Zhang

Keyword(s):

Growth Factor ◽

Disc Degeneration ◽

Lumbar Disc ◽

Akt Signaling ◽

Insulin Like Growth Factor ◽

Lumbar Disc Degeneration ◽

Phosphatidylinositol 3 Kinase ◽

Nuclear Retention ◽

Matrix Metalloproteinase 3 ◽

Regulatory Machinery

Background/Aims: The pathogenesis of Lumbar disc degeneration (LDD) has been extensively studied in the past. In particular, a role of matrix metalloproteinase 3 (MMP3) in the disease initiation and progression has been recently reported. However, an involvement of Insulin-like growth factor 1 (IGF-I)-stimulated phosphatidylinositol-3 kinase (PI3k) / Akt signaling pathway-mediated control of MMP3 in LDD has not been acknowledged. Methods: We examined the serum IGF-1 levels and activation of the receptor for IGF-1 (IGF-1R) in resected discs in patients with LDD, compared to the fractured discs from traumatized, non-LDD subjects as a control. We analyzed the effects of IGF-1 on the activation of IGF-1R, Akt and MMP3 in a human nucleus pulposus SV40 cell line (HNPSV). We transfected HNPSV cells with a constitutive nuclear FoxO1, and analyzed its effect on the activation of IGF-1R, Akt and MMP3. Results: LDD patients had significantly lower levels of serum IGF-1, and LDD discs had significantly lower levels of activated IGF-1R. IGF-1 induced phosphorylation of IGF-1R, and then phosphorylation of its downstream factor Akt in the HNPSV cells, resulting in significantly inhibition of MMP3. Further, FoxO1 nuclear retention completely abolished the inhibitory effects of IGF-1 on MMP3 in HNPSV cells. Conclusion: Together, IGF-1/Akt/FoxO1/MMP3 regulatory machinery may control the development of LDD.

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Minimally Invasive Induction of an Early Lumbar Disc Degeneration Model in Rhesus Monkeys

Spine ◽

10.1097/brs.0b013e31828b695b ◽

2013 ◽

Vol 38 (10) ◽

pp. E579-E586 ◽

Cited By ~ 12

Author(s):

Yongming Xi ◽

Jie Kong ◽

Yong Liu ◽

ZiXuan Wang ◽

Shan Ren ◽

...

Keyword(s):

Minimally Invasive ◽

Disc Degeneration ◽

Rhesus Monkeys ◽

Lumbar Disc ◽

Lumbar Disc Degeneration

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Lumbar Disc Degeneration

Acta Radiologica ◽

10.3109/02841859009173095 ◽

1990 ◽

Vol 31 (6) ◽

pp. 551-554

Author(s):

O. Tervonen ◽

S. Lahde ◽

J. Rydberg

Keyword(s):

Disc Degeneration ◽

Lumbar Disc ◽

Lumbar Disc Degeneration

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Faculty Opinions recommendation of GDF5 single-nucleotide polymorphism rs143383 is associated with lumbar disc degeneration in Northern European women.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.724435369.8399057 ◽

2011 ◽

Author(s):

Ingrid Meulenbelt ◽

Steffan Daniel Bos

Keyword(s):

Single Nucleotide Polymorphism ◽

Disc Degeneration ◽

Lumbar Disc ◽

Lumbar Disc Degeneration ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Northern European ◽

European Women

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INTERVERTEBRAL DISC DEGENERATION LINKED TO STRUCTURAL GENE VARIATIONS

Pakistan Journal of Medicine and Dentistry ◽

10.36283/pjmd8-4/012 ◽

2019 ◽

Author(s):

Saeeda Baig

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

English Language ◽

Tandem Repeats ◽

Lumbar Disc ◽

Disease Process ◽

Nucleotide Polymorphisms ◽

Structural Protein ◽

Lumbar Disc Degeneration

During the recent past focus has shifted from identifying intervertebral disc degeneration as being caused by physical exposure and strain to being linked with a variety of genetic variations. The objective of this review is to provide an up to date review of the existing research data regarding the relation of intervertebral disc degeneration to structural protein genes and their polymorphisms and thus help clearly establish further avenues where research into causation and treatment is needed. A comprehensive search using the keywords “Collagen”, “COL”, “Aggrecan”, “AGC”, “IVDD”, “intervertebral disc degeneration”, and “lumbar disc degeneration” from PubMed and Google Scholar, where literature in the English language was selected spanning from 1991 to 2019. There are many genes involved in the production of structural components of an intervertebral disc. The issues in production of these components involve the over-expression or under-expression of their genes, and single nucleotide polymorphisms and variable number of tandem repeats affecting their structures. These structural genes include primarily the collagen and the aggrecan genes. While genetic and environmental factors all come into play with a disease process like disc degeneration, the bulk of research now shows the significantly larger impact of hereditary over exposure. While further research is needed into some of the lesser studied genes linked to IVDD and also the racial variations in genetic makeup, the focus in the near future should be on establishment of genetic testing to identify individuals at greater risk of disease and deliberation regarding the use of gene therapy to prevent disc degeneration.

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