Inactivation of Osteoblast PKC Signaling Reduces Cortical Bone Mass and Density and Aggravates Renal Osteodystrophy in Mice with Chronic Kidney Disease on High Phosphate Diet
Abstract
:1. Introduction
2. Results
2.1. Experimental Results
2.1.1. Osteoblast Gαq/11 Expression and PTH Response
2.1.2. Body Weight, Mortality, and Serum Biochemistry
- Body Weight:
- Mortality:
- Biochemistry:
2.1.3. Bone Morphology (µCT)
2.1.4. Bone Planar Scintigraphy Analysis
2.1.5. Bone Histomorphometry
3. Discussion
4. Materials and Methods
4.1. Mice
4.2. Cells Cultures
4.3. Immunostaining
4.4. Cyclic AMP and IP3 Assay
4.5. Blood Chemistry Analysis
4.6. Micro-CT Analysis
4.7. Bone Planar Scintigraphy Analysis
4.8. Histomorphometric Analysis
4.9. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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WT a | KO b | WTCKD c | KOCKD d | WTHP e | KOHP f | WTCKD-HP g | KOCKD-HP | |
---|---|---|---|---|---|---|---|---|
Body weight (g) | 30.6 ± 2.6 | 29.3 ± 2.1 | 27.4 ± 1.6 | 28.7 ± 2.2 | 33.2 ± 2.8 a | 30.7 ± 3.4 e | 28.6 ± 2.1 | 25.0 ± 2.7 b,g |
Creatinine (g/L) | 0.70 ± 0.3 | 0.73 ± 0.2 | 2.01 ± 0.7 a | 2.67 ± 0.9 b | 1.08 ± 0.3 | 0.95 ± 0.3 | 3.06 ± 0.7 a | 2.69 ± 0.7 b |
Urea (mmol/L) | 7.0 ± 0.6 | 6.9 ± 1.1 | 21.9 ± 3.1 a | 24.9 ± 6.4 b | 7.0 ± 1.0 | 7.7 ± 2.2 | 16.3 ± 2.3 a | 17.7 ± 3.0 b |
Albumine (g/L) | 22.9 ± 2.1 | 20.6 ± 2.1 | 21.2 ± 2.6 | 21.5 ± 2.9 | 20.5 ± 4.4 | 20.1 ± 3.0 | 22.8 ± 2.2 | 21.9 ± 2.5 |
Calcium (mmol/L) | 2.36 ± 0.1 | 2.37 ± 0.1 | 2.53 ± 0.1 | 2.64 ± 0.04 b | 2.10 ± 0.3 a | 2.42 ± 0.2 e | 2.57 ± 0.2 a | 2.64 ± 0.2 b |
Phosphate (mmol/L) | 0.98 ± 0.2 | 1.03 ± 0.1 | 1.35 ± 0.3 a | 1.41 ± 0.4 b | 1.78 ± 0.3 a | 1.67 ± 0.2 b | 1.62 ± 0.08 a | 1.99 ± 0.5 b |
PTH (ng/L) | 54 ± 37 | 70 ± 25 | 106 ± 95 | 173 ± 108 b | 229 ± 155 a | 293 ± 170 b | 1907 ± 1099 a | 1687 ± 789.1 b |
WT a | KO b | WTCKD c | KOCKD d | WTHP e | KOHP f | WTCKD-HP g | KOCKD-HP | |
---|---|---|---|---|---|---|---|---|
n = 6 | n = 10 | n = 9 | n = 6 | n = 8 | n = 10 | n = 7 | n = 9 | |
Femoral length (mm) | 16.0 ± 0.2 | 15.9± 0.3 | 15.9 ± 0.2 | 16.1 ± 0.3 | 16.1 ± 0.2 | 15.8 ± 0.3 | 16.2 ± 0.1 | 15.7 ± 0.3 |
Cortical parameters (Diaphysis) | ||||||||
Ct.TMD (mg/cc) | 1269 ± 62 | 1144 ± 79 a | 1131 ± 47 a | 1159 ± 37 | 1202 ± 61 | 1202 ± 49 b | 1214 ± 94 | 1174 ± 70 |
Ct.Th (μm) | 197 ± 141 | 179 ± 15 a | 191 ± 12 | 183 ± 13 | 195 ± 10 | 194 ± 17 b | 209 ± 105 | 179 ± 16 g |
Ct.Ar (mm2) | 0.83 ± 0.06 | 0.77 ± 0.06 | 0.79 ± 0.04 | 0.80 ± 0.08 | 0.85 ± 0.06 | 0.82 ± 0.06 | 0.90 ± 0.07 a | 0.73 ± 0.09 g |
Cortical parameters (Metaphysis) | ||||||||
Ct.TMD (mg/cc) | 1142 ± 42 | 1059 ± 59 a | 993 ± 70 a | 1031 ± 48 | 1089 ± 60 | 1091 ± 27 | 1029 ± 122 a | 1067 ± 75 |
Ct.Th (μm) | 158 ± 12 | 141 ± 17 | 159 ± 14 | 146 ± 5 | 171 ± 16 | 156 ± 17 | 169 ± 17 | 148 ± 29 g |
Ct.Ar (mm2) | 0.76 ± 0.05 | 0.72 ± 0.07 | 0.80 ± 0.04 | 0.73 ± 0.03 | 0.89 ± 0.06 a | 0.80 ± 0.06 e | 0.86 ± 0.12 a | 0.72 ± 0.16 g |
Trabecular parameters | ||||||||
Tb TMD (mg/cc) | 765 ± 76 | 733 ± 90 | 690 ± 49 a | 712 ± 37 | 679 ± 54 a | 7116 ± 41 | 729 ± 102 | 754 ± 61 |
BV/TV (%) | 9.1 ± 1.6 | 10.3 ± 2.7 | 9.6 ± 1.9 | 11.6 ± 2.6 | 7.6 ± 1.9 | 7.9 ± 1.7 | 9.5 ± 3.0 | 7.8 ± 4.4 |
Tb.Th (μm) | 28.1 ± 3.1 | 27.4 ± 3.1 | 25.4 ± 2.2 | 28.4 ± 3.0 | 23.3 ± 3.6 a | 25.0 ± 2.3 | 26.2 ± 4.6 | 27.9 ± 4.9 |
Tb.N (/mm) | 3.2 ± 0.3 | 3.7 ± 0.8 | 3.8 ± 0.8 | 4.1 ± 0.6 | 3.3 ± 0.7 | 3.2 ± 0.5 | 3.7 ± 11 | 2.6 ± 1.0 b,g |
Tb.Sp (μm) | 283 ± 29 | 256 ± 62 | 248 ± 54 | 221 ± 38 | 295 ± 66 | 298 ± 51 | 272 ± 103 | 394 ± 143 b,g |
DA | 1.20 ± 0.06 | 1.30 ± 0.15 | 1.15 ± 0.07 | 1.26 ± 0.10 | 1.18 ± 0.06 | 1.20 ± 0.06 | 1.22 ± 0.11 | 1.21 ± 0.06 |
SMI | 2.32 ± 0.18 | 2.00 ± 0.31 | 2.46 ± 0.21 | 2.12 ± 0.63 | 2.77 ± 0.48 a | 2.43 ± 0.26 b | 2.49 ± 0.58 | 2.36 ± 0.31 |
Scintigraphic Index at Week 10 (Counts·s−1·Pixel−1·MBq−1·g−1 × 105) | Scintigraphic Index at Week 22 (Counts·s−1·Pixel−1·MBq−1·g−1 × 105) | |
---|---|---|
WT a | 11.75 ± 0.61 (n = 33) | 6.47 ± 1.55 (n = 9) |
KO b | 14.80 ± 0.70 (n = 35) a | 16.19 ± 1.63 (n = 7) |
WTCKD c | 6.28 ± 0.83 (n = 13) a | |
KOCKD d | 12.10 ± 1.19 (n = 10) b,c | |
WTHP e | 5.31 ± 1.46 (n = 6) | |
KOHP f | 12.00 ± 2.19 (n = 8) | |
WTCKD-HP g | 5.60 ± 0.74 (n = 7) a | |
KOCKD-HP h | 10.11 ± 1.52 (n = 9) b |
WT | KO | WTCKD | KOCKD | |
---|---|---|---|---|
BV/TV(%) | 26.9 ± 5.5 | 24.7 ± 4.2 | 25.9 ± 3.2 | 32.2 ± 14.6 |
BS/BV(%) | 4.0 ± 0.4 | 4.8 ± 0.5 | 3.8 ± 0.6 | 3.6 ± 1.2 |
Trabecular Thickness (µm) | 50.2 ± 5.1 | 42.0 ± 4.4 | 54.1 ± 7.4 | 63.3 ± 30.3 |
Trabecular Number | 5.3 ± 0.7 | 5.9 ± 0.5 | 4.9 ± 0.9 | 5.1 ± 0.7 |
Trabecular Separation (µm) | 139.0 ± 28.0 | 139.4 ± 28.0 | 157.9 ± 38.9 | 134.4 ± 38.8 |
OV/BV (%) | 2.8 ± 1.7 | 4.6 ± 1.4 | 3.1 ± 2.4 | 4.2 ± 1.4 |
OS/BS(%) | 11.1 ± 4.2 | 22.1 ± 9.5 | 14.8 ± 7.4 | 18.7 ± 3.8 |
Ob.S/BS (%) | 23.0 ± 3.0 | 31.9 ± 8.6 | 20.8 ± 11.5 | 29.5 ± 5.5 |
MAR (µm/d) | 1.7 ± 0.3 | 2.1 ± 0.4 | 1.5 ± 0.3 | 1.6 ± 0.4 |
Mineralizing Surface (%) | 7.0 ± 3.0 | 12.9 ± 6.6 | 4.1 ± 3.6 | 8.5 ± 3.3 |
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Zaloszyc, A.; Choquet, P.; Sayeh, A.; Bartosova, M.; Schaefer, B.; Huegel, U.; Aubertin-Kirch, G.; Healy, C.; Severac, F.; Rizzo, S.; et al. Inactivation of Osteoblast PKC Signaling Reduces Cortical Bone Mass and Density and Aggravates Renal Osteodystrophy in Mice with Chronic Kidney Disease on High Phosphate Diet. Int. J. Mol. Sci. 2022, 23, 6404. https://doi.org/10.3390/ijms23126404
Zaloszyc A, Choquet P, Sayeh A, Bartosova M, Schaefer B, Huegel U, Aubertin-Kirch G, Healy C, Severac F, Rizzo S, et al. Inactivation of Osteoblast PKC Signaling Reduces Cortical Bone Mass and Density and Aggravates Renal Osteodystrophy in Mice with Chronic Kidney Disease on High Phosphate Diet. International Journal of Molecular Sciences. 2022; 23(12):6404. https://doi.org/10.3390/ijms23126404
Chicago/Turabian StyleZaloszyc, Ariane, Philippe Choquet, Amira Sayeh, Maria Bartosova, Betti Schaefer, Ulrike Huegel, Gaëlle Aubertin-Kirch, Christopher Healy, François Severac, Sébastien Rizzo, and et al. 2022. "Inactivation of Osteoblast PKC Signaling Reduces Cortical Bone Mass and Density and Aggravates Renal Osteodystrophy in Mice with Chronic Kidney Disease on High Phosphate Diet" International Journal of Molecular Sciences 23, no. 12: 6404. https://doi.org/10.3390/ijms23126404