Fluconazole-Induced Protein Changes in Osteogenic and Immune Metabolic Pathways of Dental Pulp Mesenchymal Stem Cells of Osteopetrosis Patients
Abstract
1. Introduction
2. Results
2.1. Molecular Functional Classification of the Treatment Induced Protein Changes
2.2. Fluconazole-Induced Protein Changes Involving Osteogenesis
3. Discussion
4. Materials and Methods
4.1. Patient Samples
4.2. Cell Isolation, Culture and Fluconazole Treatment of Dental Pulp Mesenchymal Cells
4.3. Whole-Cell Lysate of Mesenchymal Stromal Cells
4.4. In-Solution Digestion of Complex Protein Mixture
4.5. Protein Identification by Label-Free Liquid Chromatography Mass Spectrometry (LC/MSE)
4.6. Data Analysis and Informatics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
SHED | Stem cells from human exfoliated deciduous teeth |
MSCs | Mesenchymal stem cells |
LC–MS/MS | Liquid chromatography–tandem mass spectrometry |
CA-II | Carbonic Anhydrase II |
CAA | Carbonic Anhydrase Activator |
HC | Healthy control |
OP | Osteopetrosis patients |
DP | Dental pulp |
MSSCs | Mesenchymal stem/stromal cells |
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Subjects | Age (Years) | Gender | Pathogenetics | Skeletal Radiology | Clinical Findings |
---|---|---|---|---|---|
OP#1 | 11 | M | c.232 + 1G > A, IVS2 + 1G > Aof the CA2 gene, (AR, RTA) | High frequency of fractures, dense bones | Dental abnormalities, developmental delay, optic atrophy/esotropia, ADHD |
OP#2 | 10 | F | c.232 + 1G > A, IVS2 + 1G > Aof the CA2 gene (AR, RTA) | Dense skull bones | Short stature, esotropia and optic atrophy |
OP#3 | 16 | F | CAII deficiency Renal Profile Low CO2, (RTA) | Diffuse increased density of skeletal bones, sclerosis more prominent in skull | ADHD, developmental delay learning disabilities, scoliosis |
OP#4 | 15 | M | CAII deficiency Renal profile Low CO2, (RTA) | Brachiocephaly, increased bone density, Erlenmeyer flask deformity | Failure to thrive, fractures, intracranial calcification |
OP#5 | 9 | M | c.232 + 1G > A;IVS2 + 1G > A (RTA), AD, CAII | Generalized increase in bone density shape normal | Calcification, fractures |
HC#1 | 11 | F | Healthy | Not indicated | No Abnormalities |
HC#2 | 9 | F | Healthy | Not indicated | No Abnormalities |
HC#3 | 10 | M | Healthy | Not indicated | No Abnormalities |
HC#4 | 16 | M | Healthy | Not indicated | No Abnormalities |
HC#5 | 9 | M | Healthy | Not indicated | No Abnormalities |
HC#6 | 13 | F | Healthy | Not indicated | No Abnormalities |
Accession | GN | Anova (p) | Max Fold Change | Highest Mean Condition | Lowest Mean Condition | Role in Bone Related Disease Association |
---|---|---|---|---|---|---|
O75718 | CRTAP | 0.0193 | 3.30 | OP-NoRx | OP-Rx | Ostegenesis Imperfecta |
P05962 | POL_HV2NZ | 0.0001 | 81.79 | OP-NoRx | OP-Rx | Not known |
P07237 | P4HB | 0.0002 | 3.32 | OP-NoRx | OP-Rx | Ostegenesis Imperfecta |
P07910 | HNRNPC | 0.0008 | 3.48 | OP-NoRx | OP-Rx | Osteoblast |
P08123 | COL1A2 | 0.0305 | 170.43 | OP-NoRx | OP-Rx | Ostegenesis Imperfecta |
P16298 | PPP3CB | 0.0010 | 42.88 | OP-NoRx | OP-Rx | Osteoclast |
P20876 | POL_HV2ST | 0.0000 | 22.26 | OP-NoRx | OP-Rx | Not known |
P29317 | EPHA2 | 0.0444 | 7.03 | OP-NoRx | OP-Rx | Osteoblast-Clast |
P36712 | L1-HAdV-12 | 0.0004 | 5.12 | OP-NoRx | OP-Rx | Not known |
P42224 | STAT1 | 0.0461 | 2.29 | OP-NoRx | OP-Rx | Osteoclast |
P46783 | RPS10 | 0.0041 | 1850.80 | OP-NoRx | OP-Rx | Osteoblast-Clast |
P50454 | SERPINH1 | 0.0000 | 5.35 | OP-NoRx | OP-Rx | Oste Imperfecta |
P50823 | VL1_HPV62 | 0.0000 | ∞ | OP-NoRx | OP-Rx | Not known |
Q5JWF2 | GNAS | 0.0015 | 42.22 | OP-NoRx | OP-Rx | Osteoblast-Clast |
Q9UBG0 | MRC2 | 0.0151 | 8.64 | OP-NoRx | OP-Rx | Osteoblast |
Q9Y696 | CLIC4 | 0.0007 | 9.14 | OP-NoRx | OP-Rx | Osteoblast |
Q00839 | HNRNPU | 0.0117 | 2.46 | OP-NoRx | OP-Rx | Osteoblast |
Q14192 | FHL2 | 0.0834 | 8.20 | OP-NoRx | OP-Rx | Osteoblast |
Q92882 | OSTF1 | 0.0109 | 4.56 | OP-NoRx | OP-Rx | Osteoblast |
Q15582 | TGFBI | 0.0009 | 4.02 | OP-NoRx | OP-Rx | Osteoblast |
P07355 | ANXA2 | 0.0000 | 6.68 | OP-Rx | OP-NoRx | Osteoblast |
Q9NR12 | PDLIM7 | 0.0004 | 4.86 | OP-Rx | OP-NoRx | Osteoblast |
Q96A33 | CCDC47 | 0.0014 | 3.43 | OP-Rx | OP-NoRx | Osteoblast |
Q96AY3 | FKBP10 | 0.0030 | 5.92 | OP-Rx | OP-NoRx | Oste Imperfata |
P38159 | RBMX | 0.0020 | 979.35 | OP-Rx | OP-NoRx | Osteoblast |
P43034 | PAFAH1B1 | 0.0085 | 39.22 | OP-Rx | OP-NoRx | Osteoclast |
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Alkhayal, Z.; Shinwari, Z.; Gaafar, A.; Alaiya, A. Fluconazole-Induced Protein Changes in Osteogenic and Immune Metabolic Pathways of Dental Pulp Mesenchymal Stem Cells of Osteopetrosis Patients. Int. J. Mol. Sci. 2023, 24, 13841. https://doi.org/10.3390/ijms241813841
Alkhayal Z, Shinwari Z, Gaafar A, Alaiya A. Fluconazole-Induced Protein Changes in Osteogenic and Immune Metabolic Pathways of Dental Pulp Mesenchymal Stem Cells of Osteopetrosis Patients. International Journal of Molecular Sciences. 2023; 24(18):13841. https://doi.org/10.3390/ijms241813841
Chicago/Turabian StyleAlkhayal, Zikra, Zakia Shinwari, Ameera Gaafar, and Ayodele Alaiya. 2023. "Fluconazole-Induced Protein Changes in Osteogenic and Immune Metabolic Pathways of Dental Pulp Mesenchymal Stem Cells of Osteopetrosis Patients" International Journal of Molecular Sciences 24, no. 18: 13841. https://doi.org/10.3390/ijms241813841
APA StyleAlkhayal, Z., Shinwari, Z., Gaafar, A., & Alaiya, A. (2023). Fluconazole-Induced Protein Changes in Osteogenic and Immune Metabolic Pathways of Dental Pulp Mesenchymal Stem Cells of Osteopetrosis Patients. International Journal of Molecular Sciences, 24(18), 13841. https://doi.org/10.3390/ijms241813841