Synovial chemokine expression and relationship with knee symptoms in patients with meniscal tears.
OBJECTIVE
In patients with knee OA, synovitis is associated with knee pain and symptoms. We previously identified synovial mRNA expression of a set of chemokines (CCL19, IL-8, CCL5, XCL-1, CCR7) associated with synovitis in patients with meniscal tears but without radiographic OA. CCL19 and CCR7 were also associated with knee symptoms. This study sought to validate expression of these chemokines and association with knee symptoms in more typical patients presenting for meniscal arthroscopy, many who have pre-existing OA.


METHODS
Synovial fluid (SF) and biopsies were collected from patients undergoing meniscal arthroscopy. Synovial mRNA expression was measured using quantitative RT-PCR. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was administered preoperatively. Regression analyses determined if associations between chemokine mRNA levels and KOOS scores were independent of other factors including radiographic OA. CCL19 in SF was measured by ELISA, and compared to patients with advanced knee OA and asymptomatic organ donors.


RESULTS
90% of patients had intra-operative evidence of early cartilage degeneration. CCL19, IL-8, CCL5, XCL1, CCR7 transcripts were detected in all patients. Synovial CCL19 mRNA levels independently correlated with KOOS Activities of Daily Living (ADL) scores (95% CI [-8.071, -0.331], P = 0.036), indicating higher expression was associated with more knee-related dysfunction. SF CCL19 was detected in 7 of 10 patients, compared to 4 of 10 asymptomatic donors.


CONCLUSIONS
In typical patients presenting for meniscal arthroscopy, synovial CCL19 mRNA expression was associated with knee-related difficulty with ADL, independent of other factors including presence of radiographic knee OA.
Division of Rheumatology, Rush University Medical Center, Chicago, IL, USA.
A
A
Nair
Division of Rheumatology, Rush University Medical Center, Chicago, IL, USA.
J
J
Gan
Department of Orthopedics, Rush University Medical Center, Chicago, IL, USA.
C
C
Bush-Joseph
Department of Orthopedics, Rush University Medical Center, Chicago, IL, USA.
N
N
Verma
Department of Orthopedics, Rush University Medical Center, Chicago, IL, USA.
M W
MW
Tetreault
Division of Rheumatology, Rush University Medical Center, Chicago, IL, USA.
K
K
Saha
Department of Biochemistry, Rush University Medical Center, Chicago, IL, USA.
A
A
Margulis
Department of Community Systems and Mental Health Nursing, Rush University Medical Center, Chicago, IL, USA.
L
L
Fogg
Division of Rheumatology & Department of Orthopedics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; Philadelphia Veterans Affairs Medical Center, Department of Medicine, Section of Rheumatology, Philadelphia, PA, USA. Electronic address: cscanz@upenn.edu.
C R
CR
Scanzello
D000203:Activities of Daily Living; D000328:Adult; D000368:Aged; D001182:Arthroscopy; D015415:Biomarkers / Q000378:metabolism; D054415:Chemokine CCL19 / Q000096:biosynthesis / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007718:Knee Injuries / Q000150:complications / Q000276:immunology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000209:etiology / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology*; D000070600:Tibial Meniscus Injuries
D015415:Biomarkers; C515460:CCL19 protein, human; D054415:Chemokine CCL19; D018925:Chemokines; D018836:Inflammation Mediators; D012333:RNA, Messenger
KOOS; Knee disability; Osteoarthritis; Relative expression; Synovitis