Synovial inflammation plays a greater role in post-traumatic osteoarthritis compared to idiopathic osteoarthritis in the Hartley guinea pig knee

Abstract

Background: The objective of this study was to evaluate the extent of stromal cell-derived factor-1's (SDF-1) involvement in the pathogenesis of idiopathic versus post-traumatic OA by comparing differences in synovial membrane morphology, SDF-1 synovial fluid (SF) concentrations, and matrix metalloproteinase-13 (MMP-13) SF concentrations.

Methods: Thirty-six 3-month-old Hartley guinea pigs were obtained and divided into 6 groups. Upon sacrifice, India Ink staining was used to evaluate gross morphology, Safranin O/Fast green staining was used to assess cartilage damage, H/E staining was employed to visualize the synovium, and SF samples were obtained for biochemical analyses. Sandwich ELISA was used to quantify the SF concentrations of SDF-1 and MMP-13.

Results: 12 month-old, idiopathic OA guinea pigs and 5.5 month-old ACLT animals had comparable cartilage damage when evaluated by the Modified Mankin Score. SDF-1 and MMP-13 concentrations were not statistically different between the two groups. The synovial membrane of the 5.5 month ACLT group had severe synovitis compared to the idiopathic OA group.

Conclusion: In this study, it was found that synovial inflammation, independent of cartilage morphology, SDF-1 concentration, and MMP-13 concentration, was markedly different between idiopathic and post-traumatic OA. These results highlight the differing morphological and biochemical profiles of post-traumatic versus idiopathic osteoarthritis and calls for a more thorough examination of the sole of the synovial membrane in the pathogenesis of post-traumatic osteoarthritis.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Brown University Institutional Animal Care and Use Committee. No Human subjects or tissues were utilized.

Consent for publication

N/A

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

India ink staining of 3-month, 12-month, 5.5-ACLT, 6.5-ACLT, 7.5-ACLT, and Sham tibial joints. The right tibia of the 5.5-ACLT joint looked most similar to that of the 12-month primary OA joint (red box). Size and intensity of the staining marked severity of the joint (dashed circles). (Original magnification, × 10)

Fig. 2

Safranin O/Fast Green staining of representative, median scoring, 3-month, 12-month, 5.5-ACLT, 6.5-ACLT, 7.5-ACLT, and Sham medial tibial condyles. The right medial tibia of the 5.5-ACLT month joint looked most similar to that of the 12 month primary OA joint (red box). (Original magnification, × 100)

Fig. 3

Modified Mankin scores of 3-month baseline (3MO), 12-month primary OA (12MO), 5.5-ACLT, 6.5-ACLT, 7.5-ACLT, and Sham (SHAM) right and left tibial joints. The right knees of the 12-month animals and 5.5-month-old animals were most similar (p = .7524), and the 12-month primary OA guinea pigs were statistically significant from the other ACLT groups (P6.5ACLT = .0425, P7.5ACLT = .0389). Error bars represent 1 standard deviation

Fig. 4

Hematoxylin/Eosin staining of representative 3-month, 12-month, 5.5-month ACLT Sham right and left tibial joints. Normal synovium is depicted with subintimal capillaries and 1-2 cell layers of synoviocytes in the 3-month joint. Surface fibrin is shown in the 12-month synovium (black arrow). Synovial hyperplasia is seen in the white arrow in the left 5.5 month joint as well as increased fibrosis of the subintimal layer (black arrow). The right 5.5-month joint has marked synovitis as pointed (white arrow) with leukocyte infiltration. The left sham knee has beginnings of fibrosis (black arrow), but no hyperplasia, and the right sham knee has scattered villous hyperplasia (black arrow). (Original magnification, × 100)

Fig. 5

a Graph of mean SDF-1 SF concentrations (ng/mL) in 3-month baseline control (3MO), 12-month primary OA (12MO), 5.5-ACLT (5.5R, 5.5 L), and Sham (ShamR, ShamL) synovial fluid. The experimental ACLT group did not have a significantly different SDF-1 concentration compared with that of the 12-month (p = .576). b Similarly, the experimental ACLT group and the 12-month primary OA SDF-1 had statistically similar MMP-13 synovial fluid concentrations (p = .470). Error bars represent one standard deviation