Accelerated Bone Loss in Transgenic Mice Expressing Constitutively Active TGF-β Receptor Type I
Abstract
:1. Introduction
2. Results
2.1. Generation of Mx1;TβRICA Mice
2.2. Mx1;TβRICA Mice Decreases Serum Calcium and Increases Serum PTH Levels
2.3. Mx1;TβRICA Mice Have Cancellous and Cortical Bone Loss in Femurs and Mandibles
2.4. Mx1;TβRICA Mice Had Decreased Bone Formation and Increased Bone Resorption
2.5. Mx1;TβRICA Mice Have Decreased Osteoblast Differentiation and Increased Osteoclast Differentiation
2.6. Mx1;TβRICA Mice Have Decreased Osteoblast and Increased Osteoclast-Related Gene Expression
2.7. Mx1;TβRICA Mice Have Increased TGF-β Signaling Leading to Decreases in RUNX2 and PTCH1 and Increases in CTSK Protein Levels
2.8. Mx1;TβRICA Mice Have Decreased Bone Hardness in Tibia
3. Discussion
4. Materials and Methods
4.1. Mice
- pRCA: 5′-TTG TGA ACA GAA GTT AAG GC-3′
- pPA: 5′-AGA AAG AAC AAT CAA GGG TCC-3′
- pHPRT-f: 5′-GAG GGA GAA AAA TGC GGA GTG-3′
- pHPRT-r: 5′-CTC CGG AAA GCA GTG AGG TAA G-3′
- Mx1-Cre-f: 5′-GTG AGT TTC GTT TCT GAG CTC C-3′
- Mx1-Cre-r: 5′-CGG TTA TTC AAC TTG CAC CA-3′
- Internal control-f: 5′-GAC AAA ATG GTG AAG GTC GG-3′
- Internal control-r: 5′-CAA AGG CGG AGT TAC CAG AG-3′
4.2. µCT Analysis
4.3. qPCR Analysis
4.4. Osteoclast Culture
4.5. Osteoblast Culture
4.6. Histomorphometry
4.7. Western Blot Analysis
4.8. Microindentation Analysis
4.9. Measurement of Bone Length
4.10. Serum Chemistry
4.11. Statistically Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameters | Tibia | Mandible | ||
---|---|---|---|---|
WT (n = 8) | Mx1;TβRICA (n = 7) | WT (n = 6) | Mx1;TβRICA (n = 6) | |
BV/TV (%) | 5.95 ± 0.62 | 2.44 ± 0.43 * | 58.73 ± 3.10 | 33.93 ± 3.07 * |
Tb.Th (μm) | 35.41 ± 2.04 | 28.92 ± 1.67 * | 66.74 ± 4.89 | 48.45 ± 3.72 * |
Tb.N (/mm) | 1.69 ± 0.18 | 0.84 ± 0.14 * | 9.04 ± 0.84 | 7.01 ± 0.31 * |
Tb.Sp (μm) | 613.02 ± 82.29 | 1350.27 ± 209.88 * | 47.77 ± 5.85 | 95.81 ± 7.77 * |
Ob.S/BS (%) | 21.38 ± 2.02 | 13.59 ± 1.48 * | 6.59 ± 0.79 | 4.40 ± 0.39 * |
N.Ob/T.Ar (/mm2) | 69.42 ± 7.57 | 22.64 ± 4.61 * | 120.11 ± 7.83 | 73.27 ± 4.32 * |
N.Ob/B.Pm (/mm) | 20.75 ± 1.96 | 13.25 ± 1.51 * | 6.80 ± 0.52 | 5.26 ± 0.34 * |
Oc.S/BS (%) | 0.37 ± 0.05 | 1.63 ± 0.30 * | 0.10 ± 0.02 | 0.60 ± 0.03 * |
N.Oc/T.Ar (/mm2) | 1.12 ± 0.17 | 2.39 ± 0.58 * | 1.54 ± 0.37 | 5.68 ± 0.50 * |
N.Oc/B.Pm (/mm) | 0.33 ± 0.03 | 1.49 ± 0.28 * | 0.08 ± 0.02 | 0.41 ± 0.04 * |
ES/BS (%) | 0.73 ± 0.08 | 2.55 ± 0.39 * | 0.18 ± 0.06 | 0.98 ± 0.06 * |
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Toejing, P.; Sakunrangsit, N.; Pho-on, P.; Phetkong, C.; Leelahavanichkul, A.; Sridurongrit, S.; Greenblatt, M.B.; Lotinun, S. Accelerated Bone Loss in Transgenic Mice Expressing Constitutively Active TGF-β Receptor Type I. Int. J. Mol. Sci. 2023, 24, 10797. https://doi.org/10.3390/ijms241310797
Toejing P, Sakunrangsit N, Pho-on P, Phetkong C, Leelahavanichkul A, Sridurongrit S, Greenblatt MB, Lotinun S. Accelerated Bone Loss in Transgenic Mice Expressing Constitutively Active TGF-β Receptor Type I. International Journal of Molecular Sciences. 2023; 24(13):10797. https://doi.org/10.3390/ijms241310797
Chicago/Turabian StyleToejing, Parichart, Nithidol Sakunrangsit, Pinyada Pho-on, Chinnatam Phetkong, Asada Leelahavanichkul, Somyoth Sridurongrit, Matthew B. Greenblatt, and Sutada Lotinun. 2023. "Accelerated Bone Loss in Transgenic Mice Expressing Constitutively Active TGF-β Receptor Type I" International Journal of Molecular Sciences 24, no. 13: 10797. https://doi.org/10.3390/ijms241310797