Development of a microcomputed tomography scoring system to characterize disease progression in the Hartley guinea pig model of spontaneous osteoarthritis

Abstract

Aim: There is potential discrepancy between human and laboratory animal studies of osteoarthritis (OA), as radiographic assessment is the hallmark of the former and histopathology the standard for the latter. This suggests a need to evaluate OA in animal models in a manner similar to that utilized in people. Our study aimed to develop a whole joint grading scheme for microcomputed tomography (microCT) images in Hartley guinea pigs, a strain that recapitulates joint changes highlighted in human spontaneous OA.

Materials and methods: Knees from animals aged 2, 3, 5, 9, and 15 months were evaluated via whole joint microCT and standard histologic scoring. Quantitative microCT parameters, such as bone volume/total volume were also collected.

Results: Both whole joint microCT and histologic scores increased with advancing age and showed strong correlation (r = 0.89. p < 0.0001). Histologic scores, which focus on cartilage changes, increased progressively with age. Whole joint microCT scores, which characterize bony changes, followed a stepwise pattern: scores increased between 3 and 5 months of age, stayed consistent between 5 and 9 months, and worsened again between 9 and 15 months.

Conclusions: This work provides data that advocates the use of a whole joint microCT scoring system in guinea pig studies of OA, as it provides important information regarding bony changes that occur at a different rate than articular cartilage changes. This grading scheme, in conjunction with histology and quantitative microCT measurements, may enhance the translational value of this animal model as it pertains to human work.

Keywords: Hartley guinea pig; histology; knee joint; microcomputed tomography; osteoarthritis.

Figure 1.

(A) Total body weight (in grams, g) for each age group of guinea pigs. (B) Comparison of total knee joint OA scores using the novel microCT grading scheme. (C) Comparison of total knee joint OARSI OA scores using toluidine blue-stained histology slides among the five age groups. Red lines indicate the mean value for each group. * P ≤ 0.05 ** P ≤ 0.01 *** P ≤ 0.001 **** P ≤ 0.0001.

Figure 2.

Representative photos from microCT evaluation of knee joints using the novel scoring system. (A) Dorsal and (B) sagittal reconstructions from a 2 month old Hartley guinea pig with no clinically significant OA lesions. This animal received a microCT OA score of 0. (C) Dorsal reconstruction from a 5 month old Hartley guinea pig. Sclerosis and small osteophytes are present on the medial femoral condyle (red arrows). and mild sclerosis of the central tibial plateau (D) Sagittal reconstruction from the same 5 month old guinea pig. Mild sclerosis of the cranial aspect of the patella and caudal tibial condyle is present. The small articular cystic changes are artifact due to the angle of the multiplanar reconstruction, which was selected to highlight the entire patella. This animal received a microCT OA score of 4. (E) Dorsal reconstruction from a 9 month old Hartley guinea pig. There is sclerosis and small osteophytes present on the medial femoral condyle (red arrow). (F) Sagittal reconstruction from the same 9 month old guinea pig. There is sclerosis along the cranial margin of the patella and at the proximal caudal end of the patella (red arrows). A large osteophyte is present on the patella (blue arrow). There are 2 cystic areas in the tibia that extend to the articular surface (green arrows). This animal received a microCT OA score of 5. (G) Dorsal reconstruction from a 15 month old Hartley guinea pig. There are 3 large osteophytes (red arrow) on the medial and lateral tibial plateau and on the medial femoral condyle. (H) Sagittal section from the same guinea pig. There is moderate subchondral sclerosis (outlined by red arrows) along the caudal tibia. (I) Dorsal reconstruction from a different plane of section from the same 15 month old guinea pig. Osteophytes on both medial and lateral tibial plateau and medial femoral condyle are still visible. There is cystic change with articular lysis (red arrow) in the tibial plateau. Subchondral bone sclerosis is also evident in the tibial plateau. (J) Sagittal reconstruction from the same animal. There is marked articular lysis of the tibial plateau (red arrow). This animal received a microCT OA score of 12.

Figure 3.

Representative photos of histologic lesions at the medial tibial surface from each age group using Toluidine blue stain. A) 2 month old with medial tibial OARSI score of 0; B) 3 month old with mild surface undulation, medial tibial OARSI OA score of 0; C) 5 month old demonstrating superficial proteoglycan loss, medial tibial OARSI OA score of 4; D) 5 month old showing articular cartilage fibrillation, medial tibial OARSI OA score 5; E) 9 month old showing proteoglycan loss into the middle zone and loss of superficial cartilage, medial tibial OARSI OA score 8; F) 9 month old demonstrating more diffuse proteoglycan loss into the deep layer with tidemark duplication, medial tibial OARSI OA score 10; G) 15 month old showing complete loss of articular cartilage, medial tibial OARSI OA score of 17; H) Another 15 month old demonstrating loss of articular cartilage and proteoglycan loss, medial tibial OARSI OA score of 18.