摘要:

AbstractIndividuals who suffer from severe joint destruction caused by the various arthritidies often undergo total joint arthroplasty. A major limitation of this treatment is the development of aseptic loosening of the prosthesis in as many as 20% of patients. The current paradigm to explain aseptic loosening proposes that wear debris generated from the prosthesis initiates a macrophage‐mediated inflammatory response by resident macrophages, leading to osteoclast activation and bone resorption at the implant interface. No therapeutic interventions have been proved to prevent or inhibit aseptic loosening. The development of therapeutic strategies is limited due to the absence of a quantitative surrogate in which drugs can be screened rapidly in large numbers of animals. We have previously described a model in which titanium particles implanted on mouse calvaria induce an inflammatory response with osteolysis similar to that observed in clinical aseptic loosening. Here, we present new methods by which the osteolysis in this model can be quantified. We determined that 6–8‐week‐old mice in normal health have a sagittal suture area of 50 (±6) μm2, which contains approximately five osteoclasts. As a result of the titanium‐induced inflammation and osteolysis, the sagittal suture area increases to 197 (±27) μm2, with approximately 30 osteoclasts, after 10 days of treatment. The sagittal suture area and the number of osteoclasts in the calvaria of sham‐treated mice remained unchanged during the 10 days. We also determined the effects of pentoxifylline, a drug that blocks the responses of tumor necrosis factor‐α to wear debris, and the osteoclast inhibitor alendronate. We found that both drugs effectively block wear debris‐induced osteolysis but not osteoclastogenesis. In conclusion, we found the measurements made with this model to be reproducible and to permit quantitative analysis of agents that are to be screened for their potential to preve

ISSN:0736-0266    

DOI:10.1002/jor.1100180602

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2000

数据来源: WILEY

摘要:

AbstractThis study evaluated the influence of the geometric configuration of the tibial joint area on the kinematics of the knee. Twenty‐two patients with noninflammatory arthritis and minor preoperative deformity were studied. They each received an AMK total knee replacement with retention of the posterior cruciate ligament. Eleven patients without any knee abnormalities were used as controls. The patients were stratified to either the flat (terminology of the manufacturer: standard) or concave (terminology of the manufacturer: constrained) polyethylene insert (n = 11 in each group). Knee kinematics were assessed 1 year after the operation by having the patient ascend a platform corresponding to an extension of the knee from 50 to 70° of flexion. During this motion, two film‐exchangers simultaneously exposed six to 13 pairs of serial stereoradiographs. The concave geometric configuration of the tibial insert resulted paradoxically in increased anterior‐posterior translations compared with the flat insect but no significant change of rotations and translations in the other directions. Compared with normal knees, the most obvious abnormality was increased anterior‐posterior translations (p<0.004). At 50° of flexion, the implants with the flat tibial polyethylene insert had displaced 2 times and the concave ones had displaced 2.5 times more posteriorly than the normal knees (p ⩽ 0.001). Less internal tibial rotation was also recorded in the flexed positions for both types of inserts compared with the normal knees (p<0.02). Four knees in four patients, who reported symptoms of instability and abnormal knee function, showed significantly increased proximal displacement of the center of the tibial plateau in the flexed position. The findings suggest that current prosthetic designs and surgical technique do not restore normal knee kinematics and indicate that design improvements should rely onin vivokinema

ISSN:0736-0266    

DOI:10.1002/jor.1100180603

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2000

数据来源: WILEY

摘要:

AbstractThis study investigated the concept of using plates to attach endoprostheses to bone after segmental resection for bone tumours in an animal model. Titanium alloy plates integrated with the prosthesis and coated with hydroxyapatite were attached to bone by screws. This type of uncemented fixation relied on the induction of periosteal bone formation into and around the plates to secure the implant to bone. Tow, three, and six‐slotted plate designs were investigated. On retrieval, each plate was securely fixed by new bone. Bone apposition on the external surface of the plates occurred through a combination of periosteal bone production, invasion of bone through slots in the plate, and bone growth over the ends of the plates. Most plates became incorporated into a remodelled cortex. Higher bone turnover rates (μm day−1) were seen in bone in the slots of the plate compared with normal cortical bone turnover (p<0.05). Significantly higher rates of turnover were measured beneath slotted parts of the plates compared with regions below the unslotted parts (p<0.05). The cross‐sectional area of bone surrounding the six‐plate implant design was significantly higher than that of the three‐plate (p<0.05) and two‐plate (p<0.05) designs. In addition, significantly more bone formed adjacent to the six‐plated implant design compared with that in the contralateral limb (p = 0.002). However, no significant difference was found when the total cortical area around the three‐plated design was compared with that of the contralateral limb (p = 0.63). In contrast, significantly less bone was measured adjacent to the two‐plate design than in the untreated limb (p = 0.001). Image analysis also demonstrated increased cortical porosity adjacent to the six‐plate design compared with the three‐plate (p = 0.004) and two‐plate (p<0.05) designs. Finite element analysis demonstrated that the six and three‐plate designs increased the second moment of area compared with that in the left tibia (p = 0.003 and 0.066, respectively). However, the attachment of the more flexible two‐plate design did not significantly increase the second moment of area compared with that in the contralateral limb (p = 0.235). It was concluded that due to both mechanical and biological effects, the hydroxyapatite‐coated plate designs generated new bone that enhanced fixation and encouraged plate integration into the load‐bearing structure of the cortex. This method of fixation may be an alternative to the use of intramedullary cemented stems in patients requiring bone tumour implants and may be the only way to preserve the joint in difficult cases where on

ISSN:0736-0266    

DOI:10.1002/jor.1100180604

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2000

数据来源: WILEY

摘要:

AbstractCarrageenan arthritis is associated with high‐turnover bone loss. We sought to determine whether the bisphosphonate pamidronate can modify this effect of inflammatory arthritis. Sixty mature, New Zealand White rabbits were randomly assigned to five groups: normal with a therapeutic dose of pamidronate (300 μg/kg/day, administered subcutaneously): arthritis (induced in the right tibiofemoral joint with 10 intraarticular carrageenan injections); arthritis with a therapeutic dose of pamidronate (300 μg/kg/day, subcutaneous); and arthritis with a low dose of pamidronate (7.5 μg/kg/day, subcutaneous). All animals received the fluorochrome calcein green (0.5 g/l/day) in drinking waterad libitumfrom days 21 to 49. Undecalcified, transverse sections of the distal femur were photographed or imaged to determine bone volume; new bone volume; resting, eroded, osteoid, and osteoblast perimeters; and ostcoclast number. Results were evaluated with analysis of variance and pairwise Bonferroni's tests. In trabecular bone adjacent to the joint affected by carrageenan arthritis, resting perimeter was substantially reduced compared with normal joints, and primary indices of osteoblast and osteoclast activity were abnormally high (p<0.001). Daily treatment with a therapeutic dose of pamidronate (300 μg/kg/day, subcutaneous) during the induction of arthritis significantly decreased new bone volume, osteoid perimeter, and osteoblast perimeter compared with the untreated arthritis group (p<0.001). Osteoclast number and eroded perimeter remained abnormally high despite treatment with pamidronate. The concomitant increase of bone volume and these osteoclast indices show that pamidronate prevents bone loss in this model of experimental inflammatory arthritis by inhibiting the resorptive activity, but not the formation or recruitment, of osteoclasts. These findings are relevant to the use of bisphosphonates in the treatment of rheumatoid arth

ISSN:0736-0266    

DOI:10.1002/jor.1100180605

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2000

数据来源: WILEY

摘要:

AbstractDedifferentiated human articular chondrocytes exhibited a wide variation in their capacity to proliferate and redifferentiate in an alginate suspension culture system. The greatest extent of proliferation and redifferentiation was seen to be dependent on the formation of clonal populations of chondrocytes and correlated mversely with the initial cell seeding density. Redifferentiating chondrocytes seeded at low density (1 × 104cells/ml alginate) compared with chondrocytes that were seeded at high density (1 × 106cells/ml alginate) showed a nearly 3‐fold higher median increase in cell number, a 19‐fold greater level of type‐II collagen mRNA expression, a 4‐fold greater level of aggrecan mRNA expression, and a 6‐fold greater level of sulfated glycosaminoglycan deposition at 4 weeks of culture. Matrix molecules from low‐density cultures were assembled into chondrocyte‐encapsulated, spherical extracellular matrices that were readily visualized in sections from 12‐week cultures stained with antibodies against types I and II collagen and aggrecan. Ultrastructural analysis of 12‐week low‐density cultures confirmed the presence of thin collagen fibrils

ISSN:0736-0266    

DOI:10.1002/jor.1100180606

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2000

数据来源: WILEY

摘要:

AbstractThe deformation behavior and mechanical properties of articular chondrocytes are believed to play an important role in their response to mechanical loading of the extracellular matrix. This study utilized the micropipette aspiration test to measure the viscoelastic properties of chondrocytes isolated from macroscopically normal or end‐stage osteoarthritic cartilage. A three‐parameter standard linear solid was used to model the viscoelastic behavior of the cells. Significant differences were found between the mechanical properties of chondrocytes isolated from normal and osteoarthritic cartilage. Specifically, osteoarthritic chondrocytes exhibited a significantly higher equilibrium modulus (0.33 ± 0.23 compared with 0.24 ± 0.11 kPa), instantaneous modulus (0.63 ± 0.51 compared with 0.41 ± 0.17 kPa), and apparent viscosity (5.8 ± 6.5 compared with 3.0 ± 1.8 kPa‐s) compared with chondrocytes isolated from macroscopically normal, nonosteoarthritic cartilage. The elastic moduli and relaxation time constant determined experimentally in this study were used to estimate the apparent biphasic properties of the chondrocyte on the basis of the equation for the gel relaxation time of a biphasic material. The differences in viscoelastic properties may reflect alterations in the structure and composition of the chondrocyte cytoskeleton that have previously been associated with osteoarthritic cartilage. Coupled with earlier theoretical models of cell‐matrix interactions in articular cartilage, the increased elastic and viscous properties suggest that the mechanical environment of the chondrocyte may be altered in osteoarthri

ISSN:0736-0266    

DOI:10.1002/jor.1100180607

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2000

数据来源: WILEY

摘要:

AbstractAbnormal mechanical loading of joints may induce degeneration of articular cartilage. Shear stress is one mode of mechanical loading that may regulate chondrocyte metabolism. We investigated the mechanism by which shear stress induces the gene encoding matrix metalloproteinase‐9, a mediator of the progressive degradation of articular cartilage in osteoarthritis.In vitroexperiments using passaged rabbit chondrocytes in monolayer culture subjected to a shear stress of 16 dyn/cm2(1.6 Pa) in a flow channel showed increased expression of the matrix metalloproteinase‐9 gene. The induction of matrix metalloproteinase‐9 appeared to depend on a region in the 5′ promoter of the gene that contains a 12–0‐tetradecanoylphorbol 13‐acetateresponsive element. Transfection experiments using a construct containing a luciferase reporter driven by a 12–0‐tetradecanoylphorbol 13‐acetate‐responsive element indicated that shear stress activated a 12–0‐tetradecanoylphorbol 13‐acetate‐responsive element‐mediated transcription in chondrocytes. Similar experiments showed that shear stress induced a matrix metalloproteinase‐9 promoter construct (matrix metalloproteinase‐9‐luciferase). Shear stress activated c‐Jun NH2‐terminal kinase, extracellular signal‐regulated kinase, and p38. Transfection o, matrix metalloproteinase‐9‐luciferase together with the dominant negative mutant of c‐Jun NH2‐terminal kinase, but not with that of extracellular signal‐regulated kinase or p38, attenuated the shearinduced matridx metalloproteinase‐9 promoter activity. In addition, transfection of constructs encoding dominant negative mutants of Ras, Rac, and Cdc42 attenuated the induction of c‐Jun transcriptional activity by shear stres. Thus, shear stimulation of chondrocytes stimulates Ras, Rac, and Cdc42, which subsequently activate c‐Jun NH2‐terminal kinase to induce a 12–0‐tetradecanoylphorbol 13‐acetate

ISSN:0736-0266    

DOI:10.1002/jor.1100180608

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2000

数据来源: WILEY

摘要:

AbstractA popular strategy in the treatment of articular cartilage lesions involves the introduction of cell suspensions into the defect void and its closure with a periosteal flap (autologous chondrocyte transplantation technique). We applied this methodology in goats and discovered that all sutured flaps (n = 6 animals) became detached from nonimmobilized joints during the recovery period. The purpose of this study was to ascertain whether postoperative restriction of joint movement could prevent the delamination of flaps. Partial‐thickness defects were created in the knee joint cartilage of 27 goats. These defects were then filled with a fibrin matrix and covered with periosteal (n = 6) or fascial (n = 21) flaps, which were sutured with simple, interrupted stitches to the surrounding tissue. The joints were immobilized by means of a modified Robert Jones bandage for periods of 2–6 weeks, after which time they were inspected for the absence or presence of flaps. In four animals, joint immobilization for 3 weeks was followed by free movement for a similar period. Four of the six periosteal flaps and two of the 21 fascial ones became delaminated after the period of immobilization. In the four goats permitted 3 weeks of free joint movement following a similar period of joint immobilization, all flaps (which had been retained up to the end of the immobilization period) became detached. These findings indicate that joint immobilization hinders the delamination of flaps but that this restriction of movement must be sustained for an undefined period of time. The nature of the tissue used for flaps also influences their rate of retention by immobilized joi

ISSN:0736-0266    

DOI:10.1002/jor.1100180609

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2000

数据来源: WILEY

摘要:

AbstractWe present a new method for quantitatively assessing the consolidation of bone regeneration by performing distraction osteogenesis in micropigs. We measuredin vivostiffness using a newly developed, revolving, bone‐healing meter. After the micropigs were killed, we obtained maximum torsional moment data for the regenerated bones by destructive mechanical testing, and we then correlated these data with the data for stiffness. We found a highly significant regression betweenin vivostiffness and maximum torsional moment (r2= 0.80), suggesting that monitoring stiffness may be useful for the prediction of bone regeneration in distraction osteogenesis. Therefore, our method may be a reliable tool for future quantitative monitoring of healing progress in patients with healing bones or in animal studies addressing treatments to increase bone formation in long‐bone defe

ISSN:0736-0266    

DOI:10.1002/jor.1100180610

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2000

数据来源: WILEY

摘要:

AbstractAlthough a number of studies have examined the fate of graft‐derived cells during the process of fusion, there remains no consensus regarding their exact contribution to bone formation within the fusion mass. We developed two chimeric mouse isograft fusion models that allowed us to track the fate of graft cells within the host fusion bed. Cortical/cancellous bone graft (1:1 ratio of pelvic to vertebral body bone) from male mice was placed between (a) the tibia and fibula or (b) the coccygeal spine transverse processes of syngeneic female hosts. Both models were characterized histologically and histochemically. Graft‐derived cells were then identified by fluorescentin situhybridization for Y‐chromosome sequences present in only the graft (male) cells. When the fusion mass was healing but not yet fused (at 1 and 2 weeks), numerous graft‐derived cells were observed throughout the fusion site. The predominant graft‐derived cell types included chondrocytes, osteoblasts, and fibroblasts. Chondrocytes arose from precursor cells in the graftde novo, as cartilage was not transplanted during the surgical procedure. By the time a mature fusion mass had formed (at 6 weeks), graft‐derived cells persisted as osteocytes within the cortical rim surrounding the fusion mass. These osteocytes likely differentiated from graft‐derived precursors that had directly formed bone, because transplanted osteocytes within cortical bone graft fragments were noted to rarely survive even at 1 and 2 weeks. Collectively, our results demonstrate for the first time that bone graft contributes cells that, in conjunction with host cells, directly form bone within the fusion mass during all phases of fusion rather than just the

ISSN:0736-0266    

DOI:10.1002/jor.1100180611

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:2000

数据来源: WILEY