Comparison of differential biomarkers of osteoarthritis with and without posttraumatic injury in the Hartley guinea pig model

Abstract

The objective was to compare biomarkers of articular cartilage metabolism in synovial fluid from Hartley guinea pig knees, with and without anterior cruciate ligament transection (ACLT), to establish whether detectable differences in biomarker levels exist between primary and secondary osteoarthritis (OA). Synovial fluid lavages and knees were obtained from 3-month (control group) and 12-month (primary OA group) animals. Another group of animals (posttraumatic OA group) underwent unilateral ACLT at 3 months, and samples were obtained 9 months postsurgery. Synovial fluid concentrations of stromal cell-derived-factor (SDF-1), collagen fragments (C2C), proteoglycan (GAG), lubricin, matrix metalloproteinase-13 (MMP-13), and Interleukin-1 (IL-1beta) were evaluated. Cartilage damage was assessed via histology. The highest concentrations of C2C and SDF-1 in synovial fluid were found in the posttraumatic OA group, moderate concentrations were found in the primary OA group, and low concentrations in the control group. GAG release in synovial fluid was similar to C2C and SDF-1. The lubricin concentrations were significantly lower in ACLT joints than either the control or 12-month primary OA groups, but not between the control and primary OA groups. Higher levels of MMP-13 and IL-1beta were detected in the joints of the posttraumatic OA group as compared to the control or primary OA groups. Histology revealed greatest OA damage in the posttraumatic OA group, followed by moderate and minimal damage in primary OA and control groups, respectively. This study indicates that the biomarkers and progression of OA may differ in the Hartley guinea pig models with and without posttraumatic OA.

(c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Figures

Fig. 1

(A) Safranin O staining and (B) the modified Mankin score showed a marked increase in cartilage damage for the 12 month ACLT knees (Group 3; n=7) as compared to the 12-month joints (Group 2; n=6) and 3-month control joints (Group 1; n=7). Loss of proteoglycan staining and cartilage destruction was evident in the Group 2 and Group 3 joints. Data are expressed as mean ± SD.

Fig. 2

The ACLT joints (Group 3) had thicker synovial membranes compared to the 12 month joints (Group 2) and the 3-month controls (Group 1).

Fig. 3

(A) The SDF-1 concentrations of the 12 month primary OA (Group 2; n=6), the 12 month ACLT (Group 3; n=7), and the 3 month control animals (Group 1; n=7) were significantly different. (B) There was a significant correlation (p

Fig. 4

(A) Mean lubricin concentrations were significantly different between the 12 month (Group 2; n=6) and the 12 month ACLT (Group 3; n=7) but there was no significant difference between the 3 month (Group 1; n=7) and 12 month (Group 2) animals. (B) There was a significant inverse correlation (p

Fig. 5

Mean concentrations of C2C in the synovial fluid lavages were significantly different between the 12 month (Group 2; n=3) and the 12 month ACLT (Group 3; n=5) animals, and the 3 month controls (Group 1; n=4).

Fig. 6

(A) Mean concentrations of GAG were significantly different between the 12 month (Group 2; n=6) and the 12 month ACLT (Group 3; n=7) animals and the 3 month controls (Group 1; n=6). (B) Western blot analysis of BC-3 qualitatively supported these findings (pooled sample; Group 1 n=3; Group 2 n=3, Group 3 n=4).

Fig. 7

Western blot analysis showed that the increased levels of MMP-13 (pooled sample; Group 1 n=3; Group 2 n=3, Group 3 n=4) and IL-1β (pooled sample; Group 1 n=3; Group 2 n=3, Group 3 n=4) release were found in the ACLT group compared to the 12-month group with primary OA. The weak bands of MMP-13 and IL-1β were detected in 3-month guinea pigs without OA changes.