Development of Substrate Degradation Enzyme Therapy for Mucopolysaccharidosis IVA Murine Model
Abstract
:1. Introduction
2. Results
2.1. Production, Purification, and Characterization of Thermostable Keratanase
2.2. In Vitro Efficacy Study of Thermostable Keratanase
2.3. Preliminary Toxicity Study of Thermostable Keratanase in Mice
2.4. Serum and Tissue Levels of KS in MPS IVA Mice after a Single Injection of Thermostable Keratanase
2.5. Therapeutic Effects of Thermostable Keratanase in MPS IVA Mice
3. Discussion
4. Materials and Methods
4.1. Production of Thermostable Keratanase from Bacillus circulans KsT202
4.2. Keratanase Assay, Endotoxin Assay, and Protein Assay
4.3. 3-Dimensional Chondrocyte Cell Culture
4.4. Preliminary Toxicity Study of Thermostable Keratanase in Mice
4.5. Intravenous Injection of Thermostable Keratanase to MPS IVA Mice
4.6. Extraction of GAG from Tissue
4.7. GAG Assay
4.8. Histopathological Staining
4.9. Statistical Analysis
Author Contributions
Funding
Conflicts of Interest
Abbreviations
3-D | 3-dimensional |
C6S | chondroitin-6-sulfate |
ECM | extracellular matrix |
ERT | enzyme replacement therapy |
GAG | glycosaminoglycans |
GALNS | N-acetylgalactosamine 6-sulfate sulfatase |
HS | heparan sulfate |
HSCT | hematopoietic stem cell transplantation |
IS | internal standard |
KS | keratan sulfate |
LC-MS/MS | liquid chromatography/tandem mass spectrometry |
MPS | Mucopolysaccharidosis |
PBS | phosphate buffered saline |
SDET | substrate degradation enzyme therapy |
TLR4 | toll-like receptor 4 |
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Score 0 (None) | Score 1 (Minimal) | Score 2 (Moderate) | Score 3 (Severe) | Total Mouse n | |
---|---|---|---|---|---|
(a) Vacuolization of chondrocyte | |||||
Control | 100% (8/8) | 0% (0/8) | 0% (0/8) | 0% (0/8) | 8 |
Untreated | 0% (0/9) | 0% (0/9) | 33% (3/9) | 67% (6/9) | 9 |
Treated | 0% (0/7) | 14% (1/7) | 57% (4/7) | 29% (2/7) | 7 |
(b) Disorganization of column structure | |||||
Control | 100% (8/8) | 0% (0/8) | 0% (0/8) | 0% (0/8) | 8 |
Untreated | 11% (1/9) | 33% (3/9) | 56% (5/9) | 0% (0/9) | 9 |
Treated | 43% (3/7) | 14% (1/7) | 43% (3/7) | 0% (0/7) | 7 |
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Sawamoto, K.; Tomatsu, S. Development of Substrate Degradation Enzyme Therapy for Mucopolysaccharidosis IVA Murine Model. Int. J. Mol. Sci. 2019, 20, 4139. https://doi.org/10.3390/ijms20174139
Sawamoto K, Tomatsu S. Development of Substrate Degradation Enzyme Therapy for Mucopolysaccharidosis IVA Murine Model. International Journal of Molecular Sciences. 2019; 20(17):4139. https://doi.org/10.3390/ijms20174139
Chicago/Turabian StyleSawamoto, Kazuki, and Shunji Tomatsu. 2019. "Development of Substrate Degradation Enzyme Therapy for Mucopolysaccharidosis IVA Murine Model" International Journal of Molecular Sciences 20, no. 17: 4139. https://doi.org/10.3390/ijms20174139