14 research outputs found

    Time dependence of changes of two cartilage layers in anterior cruciate ligament insertion after resection on chondrocyte apoptosis and decrease in glycosaminoglycan

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    <p>Abstract</p> <p>Background</p> <p>The purpose of this study is to clarify the differences in time-dependent histological changes (chondrocyte apoptosis and glycosaminoglycan (GAG) layer thickness decrease) between uncalcified fibrocartilage (UF) and calcified fibrocartilage (CF) layers at the anterior cruciate ligament (ACL) insertion after ACL resection of rabbits.</p> <p>Methods</p> <p>Forty male Japanese white rabbits underwent ACL substance resection in the right knee (resection group) and same operation without resection in the left knee (sham group). Animals were sacrificed 1, 2, 4 and 6 weeks after surgery.</p> <p>Results</p> <p>In the UF layer, the apoptosis rate in the resection group was significantly higher than that in the sham group at 1 and 2 weeks. The GAG layer thicknesses of the UF layer in the resection group at 1, 2, 4 and 6 weeks were lower than those in the sham group. In the CF layer, the apoptosis rate in the resection group was significantly higher than that in the sham group at 2 and 4 weeks. The GAG layer thickness of the CF layer in the resection group was lower than that in the sham group only at 6 weeks.</p> <p>Conclusion</p> <p>The increase in chondrocyte apoptosis rate preceded the decrease in GAG layer thickness in both layers. In the UF layer, the increase in chondrocyte apoptosis rate and the decrease in GAG layer thickness preceded those in the CF layer. Using a surviving ligament and minimizing a debridement of ACL remnant during ACL reconstruction may be important to maintain cartilage layers of ACL insertion. An injured ACL should be repaired before degenerative changes of the insertion occur.</p

    Metalloproteinases and their inhibitors—diagnostic and therapeutic opportunities in orthopedics

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    Matrix metalloproteinases (MMPs) and related enzymes (ADAMs, ADAMTS) and their inhibitors control matrix turnover and function. Recent advances in our understanding of musculoskeletal conditions such as tendinopathy, arthritis, Dupuytren's disease, degenerative disc disease, and bone and soft tissue healing suggest that MMPs have prominant roles. Importantly, MMPs are amenable to inhibition by cheap, safe, and widely available drugs such as the tetracycline antibiotics and the bisphosphonates. This indicates that these MMP inhibitors, if proven effective for any novel indication, may be quickly brought into clinical practice

    Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation

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    Bone morphogenetic protein-2 (BMP-2) is considered a promising adjuvant for the treatment of skeletal non-union and spinal fusion. However, BMP-2 delivery in a conventional collagen scaffold necessitates a high dose to achieve an efficacious outcome. To lower its effective dose, we precomplexed BMP-2 with the glycosaminoglycans (GAGs) dermatan sulfate (DS) or heparin (HP), prior to loading it into a hyaluronic acid (HA) hydrogel. In vitro release studies showed that BMP-2 precomplexed with DS or HP had a prolonged delivery compared to without GAG. BMP-2-DS complexes achieved a slightly faster release in the first 24 h than HP; however, both delivered BMP-2 for an equal duration. Analysis of the kinetic interaction between BMP-2 and DS or HP showed that HP had approximately 10 times higher affinity for BMP-2 than DS, yet it equally stabilized the protein, as determined by alkaline phosphatase activity. Ectopic bone formation assays at subcutaneous sites in rats demonstrated that HA hydrogel-delivered BMP-2 precomplexed with GAG induced twice the volume of bone compared with BMP-2 delivered uncomplexed to GAG
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