Effect of Targeted Cytokine Inhibition on Progression of Post-Traumatic Osteoarthritis Following Intra-Articular Fracture
Abstract
:1. Introduction
2. Results
2.1. Fracture Characteristics
2.2. Systemic Changes Following Treatment with INX and ANR
2.3. Effect of IL-1 Inhibition on Systemic Soluble Factor Expression Following IAF
2.4. Effect of IL-1 Inhibition on Systemic Expression of Osteochondral Markers Following IAF
2.5. Effect of IL-1 Inhibition on Local Synovial Fluid Expression of Inflammatory and Osteochondral Markers Following IAF
2.6. Effect of IL-1 Inhibition on Bone Mineral Density
2.7. Effect of IL-1 Inhibition on Bone Morphometry
2.8. Effect of IL-1 Inhibition on Histopathological Presentation of Joint Tissues
2.9. Effect of IL-1 Inhibition on IAF Cartilage Content Measured Ex Vivo by CECT
3. Discussion
4. Materials and Methods
4.1. Preparation of Interventions
4.2. Intra-Articular Fracture Model and Drug Delivery
4.3. Tissue, Blood, and Synovial Fluid Harvest
4.4. Micro-Computed Tomography
4.5. Fracture Assessment
4.6. Synovial Fluid Protein Extraction
4.7. Protein Analysis
4.8. Contrasts Enhanced µCT and Analysis
4.9. Histological and Immunohistochemical Analysis
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Ethics Statement
Disclaimer
References
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Measurement | ID | Unit | Contralateral Mean ± SEM | Saline Mean ± SEM | ANR Mean ± SEM | p-Value | ||
---|---|---|---|---|---|---|---|---|
CTRL vs. Saline | CTRL vs. ARN | Saline vs. ARN | ||||||
Tissue volume | TV | mm3 | 21.48 ± 0.72 | 17.00 ± 1.27 | 22.22 ± 2.44 | 0.060 | 0.696 | 0.058 |
Bone volume | BV | mm3 | 5.54 ± 0.16 | 3.66 ± 0.47 | 4.57 ± 0.46 | <0.001 | 0.036 | 0.083 |
Bone volume fraction | BV/TV | - | 25.84 ± 0.24 | 21.57 ± 2.29 | 20.82 ± 1.20 | 0.012 | 0.004 | 0.686 |
Tissue surface | TS | mm2 | 91.15 ± 2.81 | 73.40 ± 5.08 | 94.04 ± 9.64 | 0.024 | 0.700 | 0.023 |
Bone surface | BS | mm2 | 103.69 ± 1.77 | 65.41 ± 7.56 | 78.44 ± 7.38 | <0.001 | <0.001 | 0.104 |
Intersection surface | i.S. | mm2 | 13.06 ± 0.56 | 9.08 ± 1.24 | 11.34 ± 1.28 | 0.004 | 0.189 | 0.138 |
Specific bone surface | BS/BV | 1/mm | 18.80 ± 0.20 | 18.09 ± 0.34 | 17.31 ± 0.31 | 0.065 | <0.001 | 0.075 |
Bone surface density | BS/TV | 1/mm | 4.86 ± 0.08 | 3.88 ± 0.39 | 3.59 ± 0.18 | 0.001 | <0.001 | 0.376 |
Trabecular pattern factor | Tb.Pf | 1/mm | −3.41 ± 0.17 | 0.94 ± 0.93 | 1.95 ± 0.44 | <0.001 | <0.001 | 0.193 |
Structure model index | SMI | - | 0.89 ± 0.02 | 1.39 ± 0.14 | 1.56 ± 0.06 | <0.001 | <0.001 | 0.149 |
Trabecular thickness | Tb.Th | µm | 190.51 ± 1.62 | 213.19 ± 4.76 | 223.40 ± 3.56 | <0.001 | <0.001 | 0.040 |
Trabecular number | Tb.N | 1/mm | 1.36 ± 0.02 | 1.02 ± 0.12 | 0.93 ± 0.05 | <0.001 | <0.001 | 0.337 |
Trabecular separation | Tb.Sp | µm | 439.24 ± 4.07 | 457.57 ± 13.97 | 477.60 ± 8.08 | 0.105 | 0.002 | 0.125 |
Degree of anisotropy | DA | - | 1.79 ± 0.03 | 2.43 ± 0.12 | 1.99 ± 0.07 | <0.001 | 0.036 | <0.001 |
Fractal dimension | FD | - | 4.02 ± 0.03 | 3.60 ± 0.15 | 3.57 ± 0.07 | <0.001 | <0.001 | 0.803 |
Number of objects | Obj.N | - | 2.44 ± 0.26 | 5.88 ± 2.26 | 9.00 ± 0.98 | 0.031 | <0.001 | 0.085 |
Volume of open pore space | Po.V(op) | mm3 | 15.94 ± 0.57 | 13.34 ± 1.10 | 17.65 ± 2.10 | 0.112 | 0.292 | 0.026 |
Open porosity (percent) | Po(op) | % | 74.16 ± 0.24 | 78.43 ± 2.29 | 79.18 ± 1.20 | 0.012 | 0.004 | 0.686 |
Euler number | Eu.N | - | −279.60 ± 6.50 | −121.00 ± 20.06 | −110.00 ± 14.70 | <0.001 | <0.001 | 0.560 |
Connectivity | Conn | - | 282.30 ± 6.39 | 126.90 ± 18.38 | 119.30 ± 14.68 | <0.001 | <0.001 | 0.687 |
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Valerio, M.S.; Edwards, J.B.; Dolan, C.P.; Motherwell, J.M.; Potter, B.K.; Dearth, C.L.; Goldman, S.M. Effect of Targeted Cytokine Inhibition on Progression of Post-Traumatic Osteoarthritis Following Intra-Articular Fracture. Int. J. Mol. Sci. 2023, 24, 13606. https://doi.org/10.3390/ijms241713606
Valerio MS, Edwards JB, Dolan CP, Motherwell JM, Potter BK, Dearth CL, Goldman SM. Effect of Targeted Cytokine Inhibition on Progression of Post-Traumatic Osteoarthritis Following Intra-Articular Fracture. International Journal of Molecular Sciences. 2023; 24(17):13606. https://doi.org/10.3390/ijms241713606
Chicago/Turabian StyleValerio, Michael S., Jorge B. Edwards, Connor P. Dolan, Jessica M. Motherwell, Benjamin K. Potter, Christopher L. Dearth, and Stephen M. Goldman. 2023. "Effect of Targeted Cytokine Inhibition on Progression of Post-Traumatic Osteoarthritis Following Intra-Articular Fracture" International Journal of Molecular Sciences 24, no. 17: 13606. https://doi.org/10.3390/ijms241713606