The biomechanical and histological effects of posterior cruciate ligament rupture on the medial tibial plateau.

BACKGROUND: The objective of this study was to investigate the biomechanical and histological effects of the posterior cruciate ligament (PCL) on the medial tibial plateau. METHODS: A total of 12 cadaveric human knee specimens were collected and grouped as follows: the PCL intact group (n = 12), the anterolateral bundle rupture group (n = 6), the postmedial bundle rupture group (n = 6), and the PCL rupture group (n = 12). The strain on the anterior, middle, and posterior parts of the medial tibial plateau with an axial loading force at different flexion angles was measured and analyzed, respectively. Forty-eight rabbits were chosen for animal study: surgery was performed on the one side of each rabbit randomly (experimental group), while the other side was taken as control (control group). Every 12 rabbits were culled at each of the four selected time points to collect the medial tibial plateau for morphological and histological observation. RESULTS: The PCL rupture, either partial or complete, may generate an abnormal load on all the parts of the medial tibial plateau with axial loading at all positions. Noticeable time-dependent degenerative histological changes of the medial tibial plateau were observed in the rabbit models of PCL rupture. Compared with the control group, all the PCL rupture groups exhibited a higher expression of the matrix metalloproteinase-7 (MMP-7) and the tissue inhibitors of metalloproteinase-1 (TIMP-1) at all the time points. CONCLUSIONS: Either partial or complete PCL rupture may generate an abnormal load on all the parts of the medial tibial plateau with axial loading at all the positions and may cause cartilage degeneration on the medial tibial plateau.

Elevation of systemic matrix metalloproteinases 2 and 7 and tissue inhibitor of metalloproteinase 2 in patients with a history of Achilles tendon rupture: pilot study.

OBJECTIVES: In this study, serum levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) between patients with a history of Achilles tendon rupture and blood donor controls were compared, and their relation to mechanical properties of the tendons during healing were studied. METHODS: More than 3 years after injury, serum levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9 and MMP-13, TIMP-1 and TIMP-2 in eight patients who had Achilles tendon rupture were measured. Twelve blood donors served as controls. During the early phase of healing, the tendon modulus of elasticity was calculated from radiostereometric data and tendon cross-sectional area. RESULTS: Patients with a history of Achilles tendon rupture had increased levels of MMP-2 (median difference 10%, p=0.01), MMP-7 (median difference 15%, p=0.02) and TIMP-2 (median difference 36%, p=0.02), compared with controls. Levels of MMP-7, measured 3 years after injury, correlated inversely to tendon modulus of elasticity (r(s)=20.83, p=0.02) and positively to tendon elongation (r(s)=0.74, p=0.05) during the early phase of healing. There was a trend towards positive correlation between MMP-7 and cross-sectional area during the early phase of healing (r(s)=0.67, p=0.08). CONCLUSIONS: Patients with a history of Achilles tendon rupture appear to have elevated levels of MMP-2, MMP-7 and TIMP-2 in serum. In these pilot data, the view that the MMP-TIMP system is involved in tendinopathy is supported and that disturbances in proteolytic control might be generalised are suggested.

Apoptosis of ligamentous cells of the cranial cruciate ligament from stable stifle joints of dogs with partial cranial cruciate ligament rupture.

OBJECTIVE: To describe the presence and amount of apoptotic ligamentous cells in different areas of partially ruptured canine cranial cruciate ligaments (prCCLs) and to compare these findings with apoptosis of ligamentous cells in totally ruptured cranial cruciate ligaments (trCCLs). ANIMALS: 20 dogs with prCCLs and 14 dogs with trCCLs. PROCEDURES: Dogs with prCCLs or trCCLs were admitted to the veterinary hospital for stifle joint treatment. Biopsy specimens of the intact area of prCCLs (group A) and the ruptured area of prCCLs (group B) as well as specimens from trCCLs (group C) were harvested during arthroscopy. Caspase-3 and poly (ADP-ribose) polymerase (PARP) detection were used to detect apoptotic ligamentous cells by immunohistochemistry. RESULTS: No difference was found in the degree of synovitis or osteophytosis between prCCLs and trCCLs. No difference was found in degenerative changes in ligaments between groups A and B. A substantial amount of apoptotic cells could be found in > 90% of all stained slides. A correlation (r(s) = 0.71) was found between the number of caspase-3-and PARP-positive cells. No significant difference was found in the amount of apoptotic cells among the 3 groups. No significant correlation could be detected between the degree of synovitis and apoptotic cells or osteophyte production and apoptotic cells. CONCLUSIONS AND CLINICAL RELEVANCE: The lack of difference between the 3 groups indicates that apoptosis could be a factor in the internal disease process leading to CCL rupture and is not primarily a consequence of the acute rupture of the ligament.

Detection and distribution of apoptotic cell death in normal and diseased canine cranial cruciate ligaments.

One of the possible initiating factors in canine cranial cruciate ligament (CCL) rupture could be an abnormal pattern of ligament cell death. This study compared apoptotic cell death in sections of ruptured CCLs and normal controls, and examined nitric oxide (NO) production in joint tissues and correlated this to apoptosis. CCLs and cartilage from the lateral femoral condyle were harvested from 10 healthy dogs and 15 dogs with CCL rupture and ligaments were further processed to detect cleaved caspase-3 and to determine supernatant NO production in explant cultures. Apoptotic activity was greater in ruptured ligaments compared to controls. NO in ligaments showed a moderate but significant positive correlation with caspase-positive cells. The results suggest that increased apoptosis has a role in CCL rupture and that apoptosis may be influenced by local NO production.

Localization of cathepsin K and tartrate-resistant acid phosphatase in synovium and cranial cruciate ligament in dogs with cruciate disease.

OBJECTIVE: To localize cathepsin K and tartrate-resistant acid phosphatase (TRAP) in synovium and cranial cruciate ligament (CCL) of dogs with cruciate disease. ANIMALS: Dogs (n=15) with cruciate disease and ruptured CCL, and 12 dogs with intact CCL. METHODS: Synovium and CCL were examined histologically and cells containing cathepsin K or TRAP were identified immunohistochemically and histochemically, respectively. RESULTS: Increased cellular localization of cathepsin K and TRAP was detected in synovium and ruptured CCL in dogs with cruciate disease, when compared with tissues from dogs with intact CCL. Inflammation of synovium with TRAP+ macrophage-like cells was seen in 73% of dogs with CCL disease, but was not seen in dogs with intact CCL. The presence of cathepsin K and TRAP protein in synovium and CCL tissues was significantly correlated in dogs with CCL rupture. CONCLUSION: Inflammation of the epiligament of ruptured CCL with cathepsin K+ and TRAP+ macrophage-like cells forms part of a similar, more generalized chronic inflammatory change within the periarticular tissues of the stifle of a large proportion of dogs with CCL rupture. CLINICAL RELEVANCE: Production of matrix-degrading enzymes by the synovium may induce progressive pathologic rupture of the CCL. Therefore, these collagenolytic pathways may offer a novel target for medical therapy of joint inflammation in canine patients with cruciate disease.

The role of matrix metalloproteinases in rheumatoid tendon disease.

In rheumatoid arthritis (RA) invasive tenosynovitis is associated with an increase in tendon rupture, although little is known about the mechanisms involved. We obtained specimens of noninvasive encapsulating tenosynovium, invasive tenosynovium, and wrist joint synovium from 28 rheumatoid patients. In vitro production of the matrix metalloproteinase (MMP) enzymes, MMP-8 and -9, and total collagenase activity were measured. Invasive tenosynovium produced highest levels of the collagenase MMP-8 and displayed significantly greater ability to degrade collagen type I than encapsulating tenosynovium. Levels of the gelatinase enzyme MMP-9 were similar in all groups. These results show that invasive tenosynovium is more destructive than encapsulating tenosynovium at a molecular level, providing an explanation for the increased tendon rupture associated with invasive tenosynovitis in RA.

Evaluation of tartrate-resistant acid phosphatase and cathepsin K in ruptured cranial cruciate ligaments in dogs.

OBJECTIVE: To determine localization of tartrate-resistant acid phosphatase (TRAP) and cathepsin K in ruptured and healthy cranial cruciate ligaments (CCL) in dogs. ANIMALS: 30 dogs with ruptured CCL, 8 aged dogs without ruptured CCL, and 9 young dogs without ruptured CCL. PROCEDURE: The CCL was examined histologically and cells containing TRAP and cathepsin K were identified histochemically and immunohistochemically, respectively. RESULTS: Cathepsin K and TRAP were detected within the same cells, principally within the epiligamentous region and to a lesser extent in the core region of ruptured CCL. Numbers of cells containing TRAP and cathepsin K were significantly greater in ruptured CCL, compared with CCL from young or aged dogs, and numbers of such cells were greater in CCL from aged dogs, compared with those of young dogs. In aged dogs, small numbers of cells containing TRAP and cathepsin K were seen in intact CCL associated with ligament fascicles in which there was chondroid transformation of ligament fibroblasts and disruption of the extracellular matrix. CONCLUSIONS AND CLINICAL RELEVANCE: Ruptured CCL contain greater numbers of cells with the proteinases TRAP and cathepsin K than CCL from healthy, young, or aged dogs. Results suggest that cell-signaling pathways that regulate expression of these proteinases may form part of the mechanism that leads to upregulation of collagenolytic ligament remodeling and progressive structural failure of the CCL over time.

Evidence for the local denaturation of collagen fibrils during the mechanical rupture of human tendons.

The ends of ruptured human tendons have been examined by scanning electron microscopy. The collagen fibres taper markedly, often leading up to a coiled segment or a knot of collagen at the point of rupture. This tapering of the collagen fibres was shown to be typical of denatured collagen by its selective removal by trypsin digestion. This denaturation caused by mechanical rupture was shown to be localized at the point of rupture, the rest of the collagen fibre remaining in the native state. The possible significance of these observations to the healing of ruptured tendons is discussed.