Prediction of early sports injury of cartilage in the canine knee joint using biomarker levels in serum and synovial fluid

Qi CHANG; Changlin HUANG

ABSTRACT

BACKGROUND:

Traditional imaging examinations have lower sensitivity in diagnosing articular cartilage injury, and the effects of biomarkers in body fluid on diagnosing severity of cartilage injury should be evaluated.

OBJECTIVE:

To investigate the significance of the biomarkers, including cartilage oligomeric matrix protein (COMP), matrix metalloproteinases-1 (MMP-1), matrix metalloproteinases-3 (MMP-3) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), in serum and synovial fluid in evaluating the early sports injury of articular cartilage.

DESIGN:

A randomized controlled trial.

SETTING:

the 105 Central Hospital of Chinese PLA.MATERIALS Eighteen adult male hybrid dogs (15-25 kg, average 22.5 kg) were divided into three groups randomly ①plain-running group (n =8) the dogs ran on the plain; ② slope-running group (n =8) the dogs ran on the slope of 10°; ③control group (n =2) the dogs could move freely.

METHODS:

Dogs in the plain-running group and slope-running group were trained daily, rurning for an hour in the morning and in the afternoon respectively(total two hours per day), 4 m/s, and the training lasted for 10 weeks. Serum and synovial fluid were collected on the dayof training, and at the 2nd, 4th, 8th and 10th weeks respectively in both the plain-running group and slope-running group, and the concentrations of COMP,MMP-1, MMP-3, TIMP-1 were detected with ELISA. Standard curves were built by the standard concentrations and A values, according to which corresponding concentrations of specimens were obtained. Knee joint MRI examination was performed, and the training was canceled on the day of examination. All the dogs were killed after 10 weeks, and the knee joint cartilages weight loading region of femur condyles were observed histologically.MAIN OUTCOME

MEASURES:

Concentrations of COMP, MMP-1, MMP-3, TIMP-1 in serum and synovial fluid on the day of training, and the 2, 4, 6, 8 and 10 weeks in each group; Results of MRI examination of knee joint; Results of the histological observation of knee joint cartilage after 10 weeks.

RESULTS:

All the 18 dogs were involved in the analysis of results. ① Results of examination in serum. ② Results of examination in synovial fluid In the slope-running group, the COMP concentrations at 2, 4, 6, 8 and 10 weeks were obviously higher than those in the plain-running group (P ＜ 0.01), MMP-1 concentration at 2, 4 and 6 weeks were higher than those in the plain-running group (P ＜ 0.05-0.01), MMP-3 concentrations at 2, 4, 6 and 8 weeks were higher than those in the plain-running group (P ＜ 0.01);The MMP-3/TIMP-1 ratios at 2, 4 and 8 weeks were higher than those in the plain-running group(P ＜ 0.05-0.01).③ The concentrations of COMP,MMP-1,MMP-3 and TIMP-1 and the MMP-3/TIMP-1 ratio in serum were significantly correlated with the corresponding biomarkers in synovial fluid (r =0.631,0.502, 0.748, 0.651, 0.667, P＜ 0.01). ④ Results of histological observations In both the plain-running group and slope-running group, obvious pathological changes of articular cartilage injury were observed at 10 weeks, the activity of articular chondrocytes in the surface layer was obviously decreased, which was severer in the latter group than in the former one. ⑤Results of MRI examination Early sports injury changes of knee joint appeared at 2 weeks, and progressive aggravation occurred in both the plain-running group and slope-running group.

CONCLUSION:

Repetitive, impacted, torsional, shearing motions with long time and great intensity are easy to induce sports injury,even osteoarthritis.The sensitivity of these biomarkers is better than MRI in reflecting the pathological changes of articular cartilage.