Purpose: The objective of the present study was to evaluate whether horizontal cleavage and complex meniscus tears, which supposed to be degenerative tears, are associated with an increase of specific matrix metalloproteinases and an increased incidence of cartilage damage, in comparison with patients having other patterns of meniscal injury1,2.

Materials and Methods: Data were collected prospectively from 32 knee arthroscopies, patients were assigned by intraoperative findings due to their meniscal tear to one of two groups: “degenerative meniscal lesions” (horizontal cleavage and complex tears; n=20) or “traumatic tears” (longitudinal and radial tears; n=12). Patient data (age, duration of symptoms, mechanism of injury, body mass index [BMI]), intra-articular and radiographic findings were recorded. Samples of knee joint fluid were analyzed for the matrix matrix metalloproteinases pro-MMP-1, MMP-3 and pro-MMP-13, which are postulated to be involved in articular cartilage degradation3. Cartilage changes were classified intraoperative by Outerbridge (grade 0–4). Praeoperative bone morphology of the knee joint was graduated by Kellgren-Lawrence (Stadium 0–4). The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to assess the patients opinion about their knee and associated symptoms and function preoperative and 1.5 years postoperative.

Results: Degenerative meniscus lesions appeared predominantly at the end of fifty years of age (58.5±13.9 years), whereas other patterns of meniscal lesions happened around 30 years of age (28.7±8.1 years; P< .0001; Fig. 1 [Median]). Patients with a degenerative meniscus lesion had marginally overweight, whereas patients with a traumatic tear were in the normal range regarding the body mass index (BMI 23.7±5.3 vs. BMI 26.8±3.9; P=.044). A comparison of patients with horizontal cleavage and complex meniscal tears (“degenerative tears”) to patients with longitudinal or radial (“traumatic”) tears showed for the former increased severity of chondral lesions (Outerbridge: 2.9±1.4 vs 1.1±0.9; P=.001; Fig. 2 [Median]) and radiographic osteoarthritis (Kellgren-Lawrence: 1.9±1.5 vs 0.4±0.5; P=.004; Fig. 3 [Median]). The KOOS improved after arthroscopic treatment in the degenerativemeniscal-tear group as well as in the traumatic-tear group significantly (Total-KOOS Score preoperative: 36.5±30.7 and 38.1±24.8; Total-KOOS Score 1.5 years postoperative: 87.8±6.7 and 49.2±21.9; p=.043 and p=.012; “0” indicates extreme knee problems; “100” indicates no knee problems; Fig. 4 [Median]). Pro-MMP-13 correlated significantly with an increase of chondral lesions and radiographic osteoarthritis (r=.534; p=.003; r=.457; p=.02). MMP-3 concentrations in the synovial fluid of patients with a degenerative meniscus lesion were about 20% higher compared to patients with other patterns of meniscal lesions. No one of the investigated MMPs correlated significantly with a specific meniscal injury (Fig. 5 [Median]).

Conclusions: Complex and horizontal cleavage meniscal tears are not as benign as was previously thought and are highly associated with an increased severity of cartilage degeneration and radiographic osteoarthritis. In spite of distinct cartilage changes arthroscopic treatment improved knee-related symptoms at least on medium-term also in patients with degenerative meniscal tears. In this study, increased concentrations of the investigated MMPs did not seem to be associated with specific patterns of meniscal lesions.

Introduction: Selective COX-2 (Cyclooxygenase-2) inhibitors have been found to impede fracture healing. The effect of selective COX-2 inhibitors on tendon healing in a bone tunnel, however, is unknown.

Methods: The authors performed bilateral anterior cruciate ligament reconstructions in 32 rabbits and used peripheral quantitative computed tomography (pQCT) to compare tendon-to-bone healing between tunnel aperture and midtunnel regarding bone mineral density (BMD) and ingrowth of new bone. Each animal was assigned to one of four groups. Two groups received selective COX-2 inhibitors orally for 3 weeks (Cele-coxib; 10 mg/kg/d), the two other groups received no COX-2 inhibitors (controls). The animals were sacrificed 3 and 6 weeks after surgery. In biomechanical testing maximum load to failure and stiffness of the tendon grafts were calculated from the load displacement curve and failure modes were recorded. To assess indirectly the effect on local COX-2 activity the synovial content of Prostaglandin E2 (PGE2), the major metabolite of arachnidonic acid metabolism and catalyzed by COX-2, was measured by Enzyme-linked Immunosorbent Assay (ELISA).

Results: Animals treated with selective COX-2 inhibitors had significantly lower BMD at the tunnel aperture (P=.02). In all groups the BMD at the tunnel aperture was significantly higher in comparison with the midtunnel (P< .05). In the controls ingrowth of new bone was greater at the tunnel aperture at 3 weeks (P=.028). After 3 weeks of COX-2 inhibitor administration synovial fluid concentrations of PGE2 were significantly lowered (P=.018) and increased more than threefold by 6 weeks after surgery and 3 weeks after last drug administration (P=.022), while in the controls there was a decrease in PGE2 between week 3 and 6. At 6 weeks the controls exhibited a twofold increase in maximum load to failure (3 weeeks: 28.2±20.9 N; 6 weeks: 59.6±53.6 N; P=.394), whereas the COX-2 inhibitor treated specimens decreased 1.9fold (3 weeks: 69.3±50.5 N; 6 weeks: 37.4±16.8 N; P=.24). Maximum load to failure values correlated with PGE2 changes, but not statistically significant (r²= −0,502; p=0,056). Failure modes at 3 and 6 weeks were rupture and degloving, respectively, of the tendon graft.

Discussion: This study revealed decreased bone mineral density at the tunnel aperture at 3 weeks, an increase of the inflammatory mediator PGE2 and decreased graft stability with time after treatment with selective COX-2 inhibitors. Untreated controls appeared to have a more physiological healing course with a continuous decrease in PGE2 and an increase in graft stability. Our results suggest, that selective COX-2 inhibitors may delay tendon healing in a bone tunnel.

Objectives: The replacement tissue used for anterior cruciate ligament reconstruction undergoes extensive biologic remodelling and incorporation after implantation. These changes, in which the tendon loses some of its characteristic features and adopts those typically associated with ligaments, has been referred to as ligamentization. The purpose of this study was to identify the proinflammatory response in the healing graft in the early phase.

Methodes: Twenty New Zealand White Rabbits underwent ACL reconstruction with a semitendinosus tendon. Animals were sacrificed at 3 and 6 weeks. The harvested tissue including parts of remaining grafted tendon and genuine anterior cruciate ligament at time of the surgery as well as the tendon graft withdrawn at sacrification were prepared for immunohistochemical, histomorphometry and electromicroscopical analysis; synovia samples were taken at the sacrification as well. The tissues were immunostained for IL-1beta, TGF-beta, TNF-alpha (induction of inflammatory cascade), COX-2 (mediator of inflammatory response), Matrix Metalloproteinases (MMP-1, MMP-3, MMP-13, matrix destructive enzymes), TIMP-2 (Tissue Inhibitor of MMPs); the PGE2 (mediator of inflammatory response) content in the synovia was quantified by ELISA.

Results: At 3 weeks after surgery the COX-2+ cells accounted for 70% of all cells present in the graft tissue, and decreased to 28% at 6 weeks. Similar, IL-1beta+ cells within the tendon decreased from week 3 to week 6. Controversly, there was an increase of COX-2, IL-1beta and MMP-1 in the intercellular tissue. The numbers of COX-2+ cells and IL-1beta+ cells at 3 weeks as well as the intercellular area stained positiv for COX-2, IL-1beta and MMP-1 at 6 weeks were significantly larger compared to the genuine ACL (p =< 0.05). At 3 weeks some cells stained positiv for MMP-3 and MMP-13, but not at 6 weeks. There was a slight pericellular staining for TIMP-2 at 3 weeks. TGF-beta+ cells and TNF-alpha+ cells were almost not detectable at every time point. Thus, proinflammatory cytokines and MMPs were synthesized in the early phase after ACL reconstruction by the tendon cells and accumulated at 6 weeks in the intercellular tissue.

Conclusions: In the early phase of the graft healing after ACL reconstruction, there was a signifikant increase in proinflammatory cytokines and matrix destructive enzymes in the tendon graft. With the capability of synthesizing cytokines, tendon cells may play a critical role in tendon healing at early time points. Facing the widespread use the bias of cox-2 inhibitors on these immunologic processes has to be checked. Activating matrix destructive enzymes, cytokines appear to be crucial for connective tissue remodelling and graft stability after ACL reconstruction.