Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism
Abstract
:1. Introduction
2. Results
2.1. A Specific Set of miRNAs Is Altered in T1D and Involved in Bone Metabolism
2.2. CirculatingLevels of miR-148a and miR-21-5p Are Increased in Sera of T1D Patients vs. Control Subjects
2.3. Circulating miR-148a and miR-21-5p Levels Are Associated with BMD-Total Body (TB), PTH, and BMC-FEM
2.4. Bioinformatic Analysis Revealed that miR-148a and miR-21-5p Target Several Genes Involved in Bone Metabolism and Bone Remodeling
3. Discussion
4. Materials and Methods
4.1. Ethical Statement
4.2. Study Population
4.3. Samples Collections and Clinical Analysis
4.4. RNA Extraction
4.5. Single Assay qRT Real-Time PCR
4.6. Bioinformatic Analysis
4.7. Statistics
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Selected miRNAs | Evidences of Circulating miRNAs Differentially Expressed in T1D Patients | Evidences of miRNAs Involved in Bone Remodeling |
---|---|---|
hsa-miR-148a | Nielsen et al. 2012 [27] Seyan et al.2016 [28] Assman et al. 2017 [29] Akerman 2018 [30] | Bedene et al. 2016 [33] Seeliger et al. 2015 [34] |
hsa-miR-21-5p | Seyan et al.2016 [28] Assman et al. 2017 [29] | Li et al. 2014 [35] Seeliger et al. 2015 [34] Yang et al. 2013 [36] |
hsa-miR-214 | Erener et al. 2017 [31] | Zhao et al. 2015 [37] |
hsa-miR-375 | Seyan et al.2016 [28] | Du et al. 2015 [38] |
Samandari et al.2016 [32] | ||
Assman et al. 2017 [29] | ||
hsa-miR-27a | Nielsen et al.2012 [27] | You et al. 2016 [39] |
Zeng et al. 2017 [40] | ||
hsa-miR-24 | Seyan et al.2016 [28] | Seeliger et al. 2015 [34] |
Samandari et al.2016 [32] | ||
Assman et al. 2017 [29] | ||
Nielsen et al. 2012 [27] | ||
Erener et al. 2017 [31] |
Non-Diabetic Subjects | Type 1 Diabetic Patients | |
---|---|---|
Subjects (n) | 14 | 15 |
Male/Female (n/n) | 10/4 | 10/5 |
Age (years) | 28 ± 7.93 | 32 ± 7.9 |
Disease duration (years) | / | 15.71 ± 11.33 |
HbA1c (%) | N/A | 7.36 ± 0.80593 |
Chronic complications (n/n) | N/A | 2/15 |
Smoking habits (n/n) | N/A | 3/15 |
Other therapies (n/n) | N/A | 6/15 |
Chronic inflammatory diseases (n/n) | N/A | 4/15 |
BMI # | 24 ± 4.34 | 21 ± 1.73 # |
Ca (mg/dL) | 9.37 ± 0.50 | 9.54 ± 0.46 |
Osteocalcin (ng/mL) | 4.24 ± 1.82 | 4.50 ± 2.21 |
bALP (μg/L) | 10.5 ± 7.33 | 10.2 ± 4.72 |
25OHD (ng/mL) # | 27.9 ± 10.33 | 14.3 ± 9.83 # |
PTH (pg/mL) # | 18 ± 9.36 | 26 ± 10.23 # |
BMD TB (g/cm2) | 1.23 ± 0.11 | 1.15 ± 0.09 |
T score TB | 0.7 ± 1.18 | −0.2 ± 1.15 |
Z score TB | 0.43 ± 1.10 | 0.08 ± 1.12 |
BMC TB (g/cm2) | 2.82 ± 0.46 | 2.61 ± 0.38 |
BMD FEM (g/cm2) # | 1.156 ± 0.17 | 0.967 ± 0.13 # |
T score FEM # | 0.8 ± 1.18 | −0.8 ± 1.10 # |
Z score FEM # | 0.6 ± 1.04 | −0.8 ± 1.11 # |
BMC FEM (g/cm2) * | 37.86 ± 8.13 | 32.04 ± 4.82* |
BMD N (g/cm2) * | 1.09 ± 0.18 | 0.94 ± 0.12* |
T score N * | 0.3 ± 1.27 | −0.80 ± 1.08* |
Z score N # | 0.2 ± 1.13 | −0.8 ± 1.10 # |
BMC N (g/cm2) | 5.34 ± 1.35 | 4.40 ± 1.04 |
BMD L (g/cm2) | 1.20 ± 0.15 | 1.14 ± 0.17 |
T score L | −0.04 ± 1.24 | −0.57 ± 1.48 |
Z score L | −0.14 ± 1.26 | −0.42 ± 1.59 |
Target Gene | Gene Name | Function | Targeting miRNA |
---|---|---|---|
MAFB | V-mafavianmusculoaponeurotic fibrosarcoma oncogenehomolog B | Negatively regulates RANKL-induced osteoclast differentiation | miR-148a |
WNT1 | Wingless-type MMTV integration site family, member 1 | Canonical pathwayWnt/β catenin: stimulates osteoblast differentiation and proliferation | miR-148a |
BCL2L11 | BCL2-like 11 (apoptosis facilitator) | Induces apoptosis | miR-148a |
PTEN | Phosphatase and tensin homolog | Interacts with Canonical pathwayWnt/β catenin | miR-148a |
TGFB2 | Transforming growth factor, β 2 | Stimulates osteoblast differentiation and proliferation and bone formation | miR-148a |
IGF1 | Insulin-like growth factor 1 (somatomedin C) | Stimulates bone mineralization and positively regulates osteoblast differentiation | miR-148a |
GADD45A | Growth arrest and DNA-damage-inducible, α | Positively regulates apoptosis | miR-148a |
STAT3 | Signal transducer and activator of transcription 3 | Specifically inactivates osteoblast/osteocytes | miR-21-5p |
TGFBR1 | Transforming Growth Factor β Receptor 1 | Regulates bone resorption | miR-21-5p |
IGF1R | Insulin-like growth factor 1 receptor | Involved in bone remodeling | miR-21-5p |
BCL6 | B-Cell lymphoma 6 | Regulates osteoclast differentiation | miR-21-5p |
TGFB2 | Transforming growth factor-β 2 | Involved in osteoblast differentiation and bone remodeling | miR-21-5p |
PDCD4 | Programmed Cell Death 4 | Involved in osteoclastogenesis through cFos regulation | miR-21-5p |
SOD2 | Superoxide dismutase 2 | Controls osteoclastogenesis and maintains osteoblast differentiation | miR-21-5p |
FOXO3 | Forkhead box O-3 | Its overexpression increases bone resorption | miR-21-5p |
USP7 | Ubiquitin-specific protease 7 | Involved in osteogenic differentiation | miR-21-5p |
PTEN | Phosphatase and tensin homolog | Involved in adiponectin-induced osteogenesis | miR-21-5p |
IL-10 | Interleukin 10 | Inhibits bone resorption | miR-21-5p |
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Grieco, G.E.; Cataldo, D.; Ceccarelli, E.; Nigi, L.; Catalano, G.; Brusco, N.; Mancarella, F.; Ventriglia, G.; Fondelli, C.; Guarino, E.; et al. Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism. Non-Coding RNA 2018, 4, 37. https://doi.org/10.3390/ncrna4040037
Grieco GE, Cataldo D, Ceccarelli E, Nigi L, Catalano G, Brusco N, Mancarella F, Ventriglia G, Fondelli C, Guarino E, et al. Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism. Non-Coding RNA. 2018; 4(4):37. https://doi.org/10.3390/ncrna4040037
Chicago/Turabian StyleGrieco, Giuseppina E., Dorica Cataldo, Elena Ceccarelli, Laura Nigi, Giovanna Catalano, Noemi Brusco, Francesca Mancarella, Giuliana Ventriglia, Cecilia Fondelli, Elisa Guarino, and et al. 2018. "Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism" Non-Coding RNA 4, no. 4: 37. https://doi.org/10.3390/ncrna4040037