Do the distal femur and the proximal tibia have narrower aspect ratios in smaller knees? : A morphological analysis of osteoarthritic knees in the Japanese population using computed tomography.

BACKGROUND: Whether the distal femur and the proximal tibia have narrower aspect ratios in smaller knees has not been clarified. The purpose of this study was to confirm the dimensional characteristics of the distal femur and the proximal tibia using a novel method for consistently determining knee size. METHODS: A total of 220 Japanese osteoarthritic knees (160 female and 60 male knees) were analyzed using computed tomography. The mediolateral (ML) and the anteroposterior (AP) dimensions of the distal femur (fML, fAP) and the proximal tibia (tML, tAP) were measured. The aspect ratios (ML/AP) of the distal femur (fML/fAP) and the proximal tibia (tML/tAP) were assessed against the product of AP × ML as a consistent determination of knee size. RESULTS: The fML/fAP ratios positively correlated with knee size (fAP × fML) (r = 0.420, p < 0.001), only in the combined cohort, attributable to the narrower aspect ratios of female knees. No correlations were found between the tML/tAP ratios and knee size (tAP × tML) among females, males, nor all subjects (p = 0.299, 0.994, and 0.996, respectively). Aspect ratio correlations to knee size diverged between the three knee size indices, AP, ML, and AP × ML. CONCLUSIONS: AP × ML was the meaningful option for knee size indexing in our morphological analyses. The distal femur, but not the proximal tibia, was found to have a narrower aspect ratio in female knees in the Japanese population.

Centralization of extruded medial meniscus delays cartilage degeneration in rats.

BACKGROUND: Meniscus extrusion often observed in knee osteoarthritis has a strong correlation with the progression of cartilage degeneration and symptom in the patients. We recently reported a novel procedure "arthroscopic centralization" in which the capsule was sutured to the edge of the tibial plateau to reduce meniscus extrusion in the human knee. However, there is no animal model to study the efficacy of this procedure. The purposes of this study were [1] to establish a model of centralization for the extruded medial meniscus in a rat model; and [2] to investigate the chondroprotective effect of this procedure. METHODS: Medial meniscus extrusion was induced by the release of the anterior synovial capsule and the transection of the meniscotibial ligament. Centralization was performed by the pulled-out suture technique. Alternatively, control rats had only the medial meniscus extrusion surgery. Medial meniscus extrusion was evaluated by micro-CT and macroscopic findings. Cartilage degeneration of the medial tibial plateau was evaluated macroscopically and histologically. RESULTS: By micro-CT analysis, the medial meniscus extrusion was significantly improved in the centralization group in comparison to the extrusion group throughout the study. Both macroscopically and histologically, the cartilage lesion of the medial tibial plateau was prevented in the centralization group but was apparent in the control group. CONCLUSIONS: We developed medial meniscus extrusion in a rat model, and centralization of the extruded medial meniscus by the pull-out suture technique improved the medial meniscus extrusion and delayed cartilage degeneration, though the effect was limited. Centralization is a promising treatment to prevent the progression of osteoarthritis.

Strenuous running exacerbates knee cartilage erosion induced by low amount of mono-iodoacetate in rats.

BACKGROUND: It is still debated whether strenuous running in the inflammatory phase produces beneficial or harmful effect in rat knees. We examined (1) the dropout rate of rats during a 30-km running protocol, (2) influences of strenuous running and/or low amounts of mono-iodoacetate injection on cartilage, and (3) the effect of strenuous running on synovitis. METHODS: Rats were forced to run 30 km over 6 weeks and the dropout rate was examined. One week after 0.1 mg mono-iodoacetate was injected into the right knee, rats were forced to run either 15 km or not run at all over 3 weeks, after which knee cartilage was evaluated. Synovium at the infrapatellar fat pad was also examined histologically. RESULTS: Even though all 12 rats run up to 15 km, only 6 rats completed 30 km of running. Macroscopically, 0.1 mg mono-iodoacetate induced erosion at the tibial cartilage irrespective of 15 km of running. Histologically, 0.1 mg mono-iodoacetate induced loss of cartilage matrix in the tibial cartilage, and an additional 15 km of strenuous running significantly exacerbated the loss. Synovitis caused by mono-iodoacetate improved after running. CONCLUSIONS: Only 50% of rats completed 30 km of running because of foot problems. Strenuous running further exacerbated tibial cartilage erosion but did not influence synovitis induced by mono-iodoacetate.

Weekly injections of Hylan G-F 20 delay cartilage degeneration in partial meniscectomized rat knees.

BACKGROUND: Cross-linked hyaluronan--also called Hylan G-F 20--is a medical device developed to treat osteoarthritis of the knee. However, it is still controversial whether Hylan G-F 20 has a cartilage protective effect in trauma-induced osteoarthritis. We investigated whether Hylan G-F 20 delayed osteoarthritis progression in a partial meniscectomized rat model. METHODS: Lewis rats were used for the experiments. The anterior medial meniscus was resected at the level of the medial collateral ligament in both knees. From 1 week after the surgery, 50 µl of Hylan G-F 20 was injected weekly into the left knee and phosphate buffered saline was injected into the right knee. Cartilage was evaluated for macroscopic findings, histology with safranin-o, and expression of type II collagen at 2, 4, and 8 weeks. Synovitis was also evaluated, and immunohistochemical analysis was performed for ED1. RESULTS: Macroscopic findings demonstrated that India ink positive area, representing fibrillated cartilage, was significantly smaller in the Hylan G-F 20 group than in the control group at 2, 4, and 8 weeks (n = 5). There were no significant differences in osteophyte score between the Hylan G-F 20 group and the control group at 2, 4, and 8 weeks. Histologically, the cartilage in the medial tibial plateau was destroyed at 8 weeks in the control group, while type II collagen expression was still observed at 8 weeks in the Hylan G-F 20 group. OARSI score for cartilage histology was significantly lower in the Hylan G-F 20 group than in the control group at 4 and 8 weeks (n = 5). There were no significant differences in synovial cell number or modified synovitis score between the Hylan G-F 20 group and the control group at 2, 4, and 8 weeks (n = 5). In the Hylan G-F 20 group, foreign bodies surrounded by ED1 positive macrophages were observed in the synovium. CONCLUSION: Weekly injections of Hylan G-F 20 starting 1 week after surgery delayed cartilage degeneration after meniscectomy in a rat model. Synovitis induced by meniscectomy was not alleviated by Hylan G-F 20. Insoluble gels were observed in the synovium after the Hylan G-F 20 injection.

Cartilage Derived from Bone Marrow Mesenchymal Stem Cells Expresses Lubricin In Vitro and In Vivo.

OBJECTIVE: Lubricin expression in the superficial cartilage will be a crucial factor in the success of cartilage regeneration. Mesenchymal stem cells (MSCs) are an attractive cell source and the use of aggregates of MSCs has some advantages in terms of chondrogenic potential and efficiency of cell adhesion. Lubricin expression in transplanted MSCs has not been fully elucidated so far. Our goals were to determine (1) whether cartilage pellets of human MSCs expressed lubricin in vitro chondrogenesis, (2) whether aggregates of human MSCs promoted lubricin expression, and (3) whether aggregates of MSCs expressed lubricin in the superficial cartilage after transplantation into osteochondral defects in rats. METHODS: For in vitro analysis, human bone marrow (BM) MSCs were differentiated into cartilage by pellet culture, and also aggregated using the hanging drop technique. For an animal study, aggregates of BM MSCs derived from GFP transgenic rats were transplanted to the osteochondral defect in the trochlear groove of wild type rat knee joints. Lubricin expression was mainly evaluated in differentiated and regenerated cartilages. RESULTS: In in vitro analysis, lubricin was detected in the superficial zone of the pellets and conditioned medium. mRNA expression of Proteoglycan4 (Prg4), which encodes lubricin, in pellets was significantly higher than that of undifferentiated MSCs. Aggregates showed different morphological features between the superficial and deep zone, and the Prg4 mRNA expression increased after aggregate formation. Lubricin was also found in the aggregate. In a rat study, articular cartilage regeneration was significantly better in the MSC group than in the control group as shown by macroscopical and histological analysis. The transmission electron microscope showed that morphology of the superficial cartilage in the MSC group was closer to that of the intact cartilage than in the control group. GFP positive cells remained in the repaired tissue and expressed lubricin in the superficial cartilage. CONCLUSION: Cartilage derived from MSCs expressed lubricin protein both in vitro and in vivo. Aggregation promoted lubricin expression of MSCs in vitro and transplantation of aggregates of MSCs regenerated cartilage including the superficial zone in a rat osteochondral defect model. Our results indicate that aggregated MSCs could be clinically relevant for therapeutic approaches to articular cartilage regeneration with an appropriate superficial zone in the future.