Matrix metalloproteinase activity and prostaglandin E2 are elevated in the synovial fluid of meniscus tear patients.
OBJECTIVE
Meniscus tears are a common knee injury and are associated with the development of post-traumatic osteoarthritis (OA). The purpose of this study is to evaluate potential OA mediators in the synovial fluid and serum of meniscus tear subjects compared to those in the synovial fluid of radiographic non-OA control knees.


METHODS
Sixteen subjects with an isolated unilateral meniscus injury and six subjects who served as reference controls (knee Kellgren-Lawrence grade 0-1) were recruited. Twenty-one biomarkers were measured in serum from meniscus tear subjects and in synovial fluid from both groups. Meniscus tear subjects were further stratified by tear type to assess differences in biomarker levels.


RESULTS
Synovial fluid total matrix metalloproteinase (MMP) activity and prostaglandin E2 (PGE2) were increased 25-fold and 290-fold, respectively, in meniscus tear subjects as compared to reference controls (p < 0.05). Synovial fluid MMP activity and PGE2 concentrations were positively correlated in meniscus tear subjects (R = 0.83, p < 0.0001). In meniscus tear subjects, synovial fluid levels of MMP activity, MMP-2, MMP-3, sGAG, COMP, IL-6, and PGE2 were higher than serum levels (p < 0.05). Subjects with complex meniscus tears had higher synovial fluid MMP-10 (p < 0.05) and reduced serum TNFα and IL-8 (p < 0.05) compared to other tear types.


CONCLUSIONS
Given the degradative and pro-inflammatory roles of MMP activity and PGE2, these molecules may alter the biochemical environment of the joint. Our findings suggest that modulation of PGE2 signaling, MMP activity, or both following a meniscus injury may be targets to promote meniscus repair and prevent OA development.
a Department of Orthopaedic Surgery , Duke University Medical Center , Durham , NC , USA.|b Department of Biomedical Engineering , Duke University , Durham , NC , USA.
Betty
B
Liu
a Department of Orthopaedic Surgery , Duke University Medical Center , Durham , NC , USA.|c Duke Clinical Research Institute , Duke University Medical Center , Durham , NC , USA.
Adam P
AP
Goode
a Department of Orthopaedic Surgery , Duke University Medical Center , Durham , NC , USA.
Teralyn E
TE
Carter
a Department of Orthopaedic Surgery , Duke University Medical Center , Durham , NC , USA.
Gangadhar M
GM
Utturkar
d Duke Molecular Physiology Institute , Duke University School of Medicine , Durham , NC , USA.
Janet L
JL
Huebner
a Department of Orthopaedic Surgery , Duke University Medical Center , Durham , NC , USA.
Dean C
DC
Taylor
a Department of Orthopaedic Surgery , Duke University Medical Center , Durham , NC , USA.
Claude T
CT
Moorman
a Department of Orthopaedic Surgery , Duke University Medical Center , Durham , NC , USA.
William E
WE
Garrett
d Duke Molecular Physiology Institute , Duke University School of Medicine , Durham , NC , USA.|e Department of Medicine , Duke University School of Medicine , Durham , NC , USA.
Virginia B
VB
Kraus
f Department of Orthopaedic Surgery , Washington University and Shriners Hospitals for Children - St. Louis , St. Louis , MO , USA.
Farshid
F
Guilak
a Department of Orthopaedic Surgery , Duke University Medical Center , Durham , NC , USA.|b Department of Biomedical Engineering , Duke University , Durham , NC , USA.
Louis E
LE
DeFrate
a Department of Orthopaedic Surgery , Duke University Medical Center , Durham , NC , USA.|g Department of Pathology , Duke University Medical Center , Durham , NC , USA.
Amy L
AL
McNulty
D000328:Adult; D015415:Biomarkers / Q000097:blood; D003710:Demography; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D007718:Knee Injuries / Q000097:blood / Q000201:enzymology; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood / Q000378:metabolism*; D000072600:Meniscus / Q000293:injuries* / Q000378:metabolism*; D008875:Middle Aged; D013582:Synovial Fluid / Q000378:metabolism*
D015415:Biomarkers; D020782:Matrix Metalloproteinases; D015232:Dinoprostone
Collagen; cartilage oligomeric matrix protein; inflammatory; interleukin; metabolic; proteoglycan; tumor necrosis factor alpha