Synovial inflammation in patients undergoing arthroscopic meniscectomy: molecular characterization and relationship to symptoms

Abstract

Objective: Traumatic and degenerative meniscal tears have different anatomic features and different proposed etiologies, yet both are associated with the development or progression of osteoarthritis (OA). In established OA, synovitis is associated with pain and progression, but a relationship between synovitis and symptoms in isolated meniscal disease has not been reported. Accordingly, we sought to characterize synovial pathology in patients with traumatic meniscal injuries and determine the relationships between inflammation, meniscal and cartilage pathology, and symptoms.

Methods: Thirty-three patients without evidence of OA who were undergoing arthroscopic meniscectomy for meniscal injuries were recruited. Pain and function were assessed preoperatively; meniscal and cartilage abnormalities were documented at the time of surgery. Inflammation in synovial biopsy specimens was scored, and associations between inflammation and clinical outcomes were determined. Microarray analysis of synovial tissue was performed, and gene expression patterns in patients with and those without inflammation were compared.

Results: Synovial inflammation was present in 43% of the patients and was associated with worse preoperative pain and function scores, independent of age, sex, or cartilage pathology. Microarray analysis and real-time polymerase chain reaction revealed a chemokine signature in synovial biopsy specimens with increased inflammation scores.

Conclusion: Our findings indicate that in patients with traumatic meniscal injury undergoing arthroscopic meniscectomy without radiographic evidence of OA, synovial inflammation occurs frequently and is associated with increased pain and dysfunction. Synovia with increased inflammation scores exhibit a unique chemokine signature. Chemokines may contribute to the development of synovial inflammation in patients with meniscal pathology; they also represent potential therapeutic targets for reducing inflammatory symptoms.

Figure 1

Histology of synovial membrane inflammation in meniscectomy patients. Synovial biopsies from meniscectomy patients taken at the time of surgery were fixed, embedded, and thin-sectioned before being stained with Haematoxylin and Eosin. Inflammation was graded as described in Materials and Methods. Low power (5X objective) photomicrographs of representative sections from patients with grade 0 (panel A), 1 (panel B) and 2 (panel C) inflammation based on the presence of perivascular mononuclear cell accumulations (black arrows) are pictured. Panel A and C depict sections from two patients subjected to microarray analysis.

Figure 2

Real-time PCR validation of A. IL-8, B. CCL5, C. CCR7 and D. CCL19 measured in thirty-seven synovial biopsies from eighteen meniscectomy patients. RE = Relative Expression calculated relative to the mean in biopsies without inflammation, after normalizing to GAPDH. IL-8, CCL5, and CCR7 were all detected more frequently in biopsies exhibiting synovial inflammation (■) than in biopsies that did not (●). GEE modeling revealed significant associations between inflammation and CCL5 (p=0.0307) and CCL19 (p= 0.0096). P-values for IL-8 and CCR7 were 0.0649 and 0.066.

Figure 3

Association of chemokine levels and Lysholm scores. Chemokine expression was measured by real-time PCR in suprapatellar synovial biopsies (n=12 for CCR7, n=9 for CCL19) from meniscectomy patients. Associations between chemokine expression and Lysholm scores were tested using Spearman’s non-parametric correlation test. A. CCR7 relative expression (RE) levels and B. CCL19 RE levels were significantly associated with Lysholm scores.