Suppression of cartilage degeneration by intra-articular injection of heparan sulfate 6-O endosulfatase in a mouse osteoarthritis model.

We previously reported that heparan sulfate 6-O endosulfatases (Sulfs) were expressed in articular cartilage, and that the Sulf-1 knockout mouse developed severe knee osteoarthritis. In this study, we hypothesised that intra-articular injection of Sulf-1 would prevent cartilage degeneration. After confirming that 1 mg/ml Sulf-1 did not induce ATDC5 cell death in vitro, gene expression of type II collagen and matrix metalloproteinase (MMP)-13 in the presence of Sulf-1 (1 100 ng/ml) were determined by quantitative real-time polymerase chain reaction. Sulf-1 was also injected intra-articularly into mice following surgical destabilisation of the medial meniscus to produce a model of osteoarthritis, and cartilage degeneration was evaluated by safranin O and MMP-13 staining. We also investigated fibroblast growth factor 2 (FGF2)/extracellular signal-regulated kinase (Erk) cell signalling by western blotting. Exposure to Sulf-1 in vitro increased type II collagen expression and decreased MMP-13 expression in a concentration-dependent manner. Sulf-1 injection into the mouse osteoarthritic knee significantly suppressed glycosaminoglycan loss and MMP-13 expression. Erk1/2 signalling pathway activation was significantly reduced by Sulf-1 and FGF2. These findings indicate that Sulf-1 prevents cartilage degeneration by suppressing MMP-13 via an effect on FGF2/Erk1/2 signalling.

Correlation between varus knee malalignment and patellofemoral osteoarthritis.

PURPOSE: To evaluate the relationship between patellofemoral osteoarthritis (OA) and varus OA of the knee with a focus on the location of joint space narrowing. METHODS: Eighty-five patients scheduled to undergo total knee arthroplasty caused by varus OA were enrolled in this study. The relationship between patellofemoral OA and varus knee malalignment was elucidated. To determine the alignment of the patellofemoral joint in varus knees, patellar tilt, and the tibial tuberosity-trochlear groove (TT-TG) distance were measured, and patellofemoral OA was classified using computed tomography. RESULTS: The femorotibial angles in patients with stage II-IV patellofemoral OA were significantly larger than those in patients with stage I patellofemoral OA, and the patellar tilt in patients with stage II-IV patellofemoral OA and the TT-TG distance in patients with stage IV patellofemoral OA were significantly larger than those in patients with stage I patellofemoral OA. The TT-TG distance was strongly correlated with patellar tilt (R(2) = 0.41, P < 0.001). Patellofemoral joint space narrowing was mainly noted at the lateral facet, and it was found on both sides as patellofemoral OA worsened. CONCLUSION: Varus knee malalignment was induced by patellofemoral OA, especially at the lateral facet. Patellar tilt and the TT-TG distance are considered critical factors for the severity of patellofemoral OA. Understanding the critical factors for patellofemoral OA in varus knees such as the TT-TG distance and patellar will facilitate the prevention of patellofemoral OA using procedures such as high tibial osteotomy and total knee arthroplasty to correct knee malalignment. LEVEL OF EVIDENCE: Retrospective cohort study, Level III.

Chondrocyte clusters adjacent to sites of cartilage degeneration have characteristics of progenitor cells.

The purpose of this study was to investigate the site-specific characteristics and roles of chondrocyte clusters in human knee osteoarthritis. Cartilage explants were obtained from 45 knees undergoing total knee replacement surgery. The explants were taken from 4 locations in the knee: the medial femoral condyle, the medial posterior femoral condyle (MPC), the lateral femoral condyle, and the lateral posterior femoral condyle (LPC). Cartilage degeneration, cell density, and cell arrangement were compared histologically. A live/dead cell viability assay and immunohistochemical analyses using antibodies against STRO-1, FGF2, and Ki-67 were performed. Cell proliferation and cartilaginous nodule production in MPC and LPC explants in monolayer culture were compared. Finally, MPC cartilage explants were cultured to observe histological changes. The cell density of the MPC explants was higher than that of the LPC because of clustering. MPC explants contained more live cells than the LPC did, and the expression of IHC markers in MPC explants was higher than that in LPC. Chondrocytes from MPC proliferated faster and produced more nodules in monolayer culture than those from the LPC and MPC explants were repaired during organ culture. In conclusion, chondrocyte clusters adjacent to severe cartilage degeneration have specific characteristics, with progenitor and proliferative potential.

A new method for meniscus repair using type I collagen scaffold and infrapatellar fat pad.

AIM: The aim of this study was to investigate a new method for meniscal repair by combinative transplantation with type I collagen scaffold and infrapatellar fat pad. METHODS: Two-mm cylindrical defects at the anterior part of bilateral medial menisci were prepared in nine Japanese white rabbits. The 18 knees were equally divided into three groups: I, no treatment; II, collagen scaffold transplantation; and III, collagen scaffold and infrapatellar fat pad transplantation. Another three rabbits (six knees) underwent sham surgery and served as controls. Rabbits were sacrificed at eight weeks after transplantation. Surface area of the medial meniscus was evaluated using macrophotographs. Ishida score for meniscal regeneration was used for assessment. To evaluate the composition of regenerated tissue, immunohistochemistry was analyzed with anti-type I and anti-type II collagen antibodies, and anti-Ki67 antibody. To investigate the effects of collagen scaffold on human meniscus, cells were isolated from human meniscus and infrapatellar fat pad, and cultured with collagen scaffold for three weeks. After that, gene expression was evaluated by using quantitative real-time polymerase chain reaction. RESULTS: In group I, the meniscus shrank anterior to posterior, and the surface area was significantly less than that of normal meniscus. However, the surface area was maintained in group III. Ishida score and Ki67-positive cell ratio in group III were significantly higher than that in any other group, and staining with type I and type II collagen was similar to that of the control. Expression of matrix metalloproteinase was significantly lower in cocultures of collagen scaffold, meniscus cell, and infrapatellar fat pad cell than in monocultured meniscus cell, and expression of interleukin-1ß was not increased. CONCLUSION: This new method for meniscal repair by combinative transplantation with type I collagen scaffold and infrapatellar fat pad showed meniscal regeneration and potential for suppressing inflammation.

Three-dimensional transfer of the tibial tuberosity for patellar instability with patella alta.

BACKGROUND: Although patellar instability can be treated with several surgical procedures, the appropriate surgical treatment for patellar instability with patella alta has not yet been investigated. The objective of this study is to find out whether three-dimensional transfer of the tibial tuberosity elicits good knee functionality with improved patella alta and prevents further patellar dislocation. METHODS: Twelve knees (10 patients) underwent surgery for patellar instability with patella alta from 2007 to 2011. The surgery performed was a three-dimensional transfer for the anteromedial distalization of the tibial tuberosity. Predisposing anatomical factors for patellar instability were evaluated preoperatively; femorotibial angle (FTA), patella alta (IS ratio), trochlear dysplasia (sulcus angle) and tilting angle (lateral tilt). The function of the knee was assessed before and after surgery by Lysholm and Kujala score. RESULTS: Before surgery, the IS ratio was 1.34 ± 0.13, lateral tilt was 22.4° ± 6.5°, and the sulcus angle was 151.7° ± 8.3°, indicating patella alta, laterality, and trochlear dysplasia. After surgery, the IS ratio and lateral tilt significantly improved to 0.95 ± 0.13, and 10.6° ± 3.4°, respectively. FTA and sulcus angle were not altered. Lysholm and Kujala score improved from 63.8 to 94.7 and 67.0 to 94.1 points, respectively. Most patients displayed good outcomes except for one patient who suffered re-dislocation by hitting their knee on the floor, 2.5 years after surgery. CONCLUSION: Three-dimensional tibial tuberosity transfer was shown to correct the patella position and result in a good clinical outcome. This method is introduced as an alternative surgery for patellar instability with patella alta.

Systolic anterior motion (SAM) of the posterior mitral leaflet: left ventricular outflow tract obstruction in a patient without left ventricular hypertrophy.

Systolic anterior motion (SAM) of the anterior mitral leaflet with mitral-septal contact was generally thought to be a major contributor to dynamic left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy. We report an interesting case of SAM of the posterior mitral leaflet in a patient without left ventricular hypertrophy, which led to dynamic left ventricular obstruction.