bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human breast cancer induces osteoclast activation and increases the number of osteoclasts at sites of tumor osteolysis
Authors: Closhisy Denis R , Palkert Diane , Ramnaraine Margaret L. R. , Pekurovsky Ilya , Oursler Merry Jo 
Published: February 2005

AbstractThe cellular mechanism through which osseous breast cancer metastases induce the focal destruction of bone (tumor osteolysis) is unknown. An athymic mouse model designed for the study of tumor osteolysis was developed and the influence of two human breast cancer tumors on bone was studied. Tumor‐induced osteolysis occurred between 7 and 10 weeks after inoculation of mouse femora with MDA‐MB‐231 or MDA‐MB‐435s breast cancer cells. An increase in osteoclast number and an increase in osteoclast size (area) were detected when tumor‐bearing and sham‐injected limbs were compared. In vitro analysis of the influence of the tumor‐conditioned medium on osteoclast‐mediated bone resorption revealed that this conditioned medium stimulated the resorption by increasing both the number of osteoclasts bound to bone and the number of bone resorption pits formed per osteoclast. In addition, in vitro analysis of the influence of breast cancer tumor cells on osteoclast formation or survival, or both, demonstrated that breast cancer cells induced a dramatic increase in the number of osteoclasts detected in culture. Taken in total, these findings suggest that human breast cancer tumors induce osteolysis by enhancing osteoclast adherence to bone, stimulating osteoclast‐mediated bone resorption, and either prolonging the survival of osteoclasts or increasing osteoclast formation.
In vitro bone biocompatibility of poly(anhydride‐co‐imides) containing pyromellitylimidoalanine
Authors: Attawia Mohamed A. , Uhrich Kathryn E. , Botchwey Edward , Langer Robert , Laurencin Cato T. 
Published: February 2005

AbstractPoly(anhydride‐co‐imides) are currently under study for applications involving bone. The cytotoxicity of a series of poly(anhydride‐co‐imides) with osteoblast‐like cells (MC3T3‐E1) was evaluated. The imide component of the copolymers was based on pyromellitylimidoalanine and the anhydride component was based on either sebacic acid or 1,6‐bis(carboxyphenoxy)hexane. Cell adhesion and proliferation on the surfaces of the polymer discs were observed by environmental scanning electron microscopy. During the first 24 hours of attachment, the cells showed normal morphology when cultured on copolymers containing 1,6‐bis(carboxyphenoxy)hexane. The cells did not adhere to the polymers containing sebacic acid, probably due to the rapid degradation of the polymer surfaces. Concurrently, the effects of polymer breakdown products on osteoblast‐like cells were evaluated by studying their proliferation (cell numbers), viability (dye exclusion), morphology (light microscopy), and phenotypic expression. The morphology of osteoblast‐like cells cultured in the presence of the polymer breakdown products pyromellitylimidoalanine and pyromellitic acid was found to be similar to that of the same cells grown on tissue culture polystyrene and consisted of a characteristic polygonal shape. With use of a monoclonal antibody to osteocalcin, these cells were shown to demonstrate preserved osteoblast phenotype with growth over a 21‐day period. In addition, the cells reached confluency after 3–4 days, similar to cells grown on tissue culture polystyrene. This in vitro evaluation showed that the poly(anhydride‐co‐imides) evaluated are non‐cytotoxic and may be viable biomaterials for orthopaedic applications.
Biomechanical comparison of calf and human spines
Authors: Wilke Hans‐Joachim , Krischak Stefan , Claes Lutz 
Published: February 2005

AbstractGiven the limited availability of human cadaveric specimens and their potential risk of infection, calf spines have been used as substitutes for human spines in the evaluation of spinal implants. Few bio‐mechanical data comparing calf and human spines are available, however. The purpose of this study was to determine the biomechanical properties of the calf spine and to compare them with properties previously reported for the human spine. We determined the range of motion, neutral zone, and stiffness of thoracic and lumbar calf spines (T6 to L6) under pure moment loading in flexion‐extension, axial rotation, and lateral bending. These properties were shown to be similar to those of the human spine. The results suggest that the calf spine can be used as a substitute for the human spine in some in vitro tests.
Effect of tibial attachment location on the healing of the anterior cruciate ligament freeze model
Authors: Bush‐Joseph C. A. , Cummings J. F. , Buseck M. , Bylski‐Austrow D. I. , Butler D. L. , Noyes F. R. , Grood E. S. 
Published: February 2005

AbstractWe studied the healing response of a devitalized anterior cruciate ligament to a treatment of initial anterior‐posterior joint translation in goats. Devitalization and devascularization were achieved by five successive freeze‐thaw cycles. Anterior‐posterior translation was surgically altered by an osteotomy of the tibial attachment of the devitalized ligament and its reattachment either in the anatomical position or in a position 5 mm posterior. Six weeks after the first surgery, the same procedure was performed on the contralateral limb, except that the ligament was reattached in the alternate position. Six months after the initial surgery, femur‐anterior cruciate ligament‐tibia specimens were tested to determine their structural and mechanical material properties. Anatomic ligament placement resulted in reduced anterior‐posterior translation (p < 0.05) and greater anterior joint stiffness (p < 0.05). Maximum load (p < 0.05) and ligament stiffness (p < 0.01) also were greater for the anatomically placed anterior cruciate ligaments. The maximum load for anatomically placed ligaments averaged 1.625 ± 211 N (SEM). The strength of the posteriorly placed anterior cruciate ligament, 895 ± 164 N. was similar to results of historical anterior cruciate autograft reconstructions. Ligament failure occurred near the tibial insertion in the posteriorly placed ligaments more often than in the anatomically placed ligaments (four of five times compared with one of five times). Ligament failure near the tibial insertion occurred with lower mean maximum load than failure at the midsubstance or by bone avulsion (796 compared with 1.592 N: p < 0.05). These data support the hypothesis that ligament laxity is important to the healing and remodeling of anterior cruciate ligament grafts.
Patellar tendon and anterior cruciate ligament have different mitogenic responses to platelet‐derived growth factor and transforming growth factor β
Authors: Spindler Kurt P. , Imro Amy K. , Mayes Charles E. , Davidson Jeffrey M. 
Published: February 2005

AbstractThe healing responses of the anterior cruciate ligament and the patellar tendon differ markedly. The anterior cruciate ligament fails to heal, whereas the patellar tendon heals slowly. The basis of these differences is unknown. Since cellular proliferation is a critical element of healing, we investigated the response to explants of anterior cruciate ligament and patellar tendon from sheep knees to platelet‐derived growth factor‐AB and transforming growth factor β1 as a function of time and dose. Explants cultured for 48, 72, and 96 hours with transforming growth factor β1 (0‐100 ng/ml) or platelet‐derived growth factor‐AB (0‐200 ng/ml) were radiolabeled for the final 24 hours with [3H]thymidine, and DNA synthesis was quantified as trichloroacetic acid‐precipitable radioactivity normalized to dry tissue weight. Statistical analyses (analysis of variance) showed that transforming growth factor β1 induced a significant proliferative response in the anterior cruciate ligament at 96 hours with equivalent responses at 10.50, and 100 ng/ml, whereas the patellar tendon only responded to one condition, 10 ng/ml at 96 hours. Conversely, the patellar tendon had a significant dose‐dependent response to platelet‐derived growth factor‐AB at 72 and 96 hours, whereas the anterior cruciate ligament showed no proliferative response to platelet‐derived growth factor‐AB. The minimal response of anterior cruciate ligament to platelet‐derived growth factor‐AB could explain, at least in part, the poor repair capacity of this tissue. The response of the anterior cruciate ligament to transforming growth factor β suggests that exogenous transforming growth factor β may promote initial healing. Although growth factors have the potential to modulate soft‐tissue repair, tissue responses in tendons and ligaments may vary at different anatomic sites.
Spatial distribution of CD44 and hyaluronan in the proximal tibia of the growing rat
Authors: Noonan Kenneth J. , Stevens Jeff W. , Tammi Raija , Tammi Markku , Hernandez José A. , Midura Ronald J. 
Published: February 2005

AbstractCD44 has been described as a cell surface hyaluronan receptor present on a variety of different cells, and it is generally assumed to be prevalent in most connective tissues that contain hyaluronan. A major aim of this study was to test that presumption by localizing CD44 and hyaluronan within several tissues of the proximal tibia of the growing rat. Comparison of these profiles would reveal whether CD44 and hyaluronan co‐localize with high fidelity, as would be expected if CD44 were a major hyaluronan binding protein. Using in situ hybridization and immunohistochemistry, CD44 was identified on osteoclasts, chondroclasts, osteocytes, hematopoietic marrow cells, synovial cells, and connective tissue fibroblasts (ligaments, tendons, and fascia). Although the majority of osteocytes expressed CD44, reduced expression was observed for osteoblasts and osteoprogenitor cells. Additionally, CD44 was not detected on chondrocytes from epiphyseal and metaphyseal growth cartilages or in meniscal fibrocartilage. Using biotinylated G1 domain from aggrecan and link protein, hyaluronan was observed in the maturational and hypertrophic zones of all growth cartilages, the synovium and other fibroblastic connective tissues, regional areas of the periosteum and endosteum (around osteoblasts, osteoprogenitor cells, and osteoclasts), osteocyte lacunae, and surrounding blood vessels. In regions of co‐localization for CD44 and hyaluronan, it seems that CD44 is a likely hyaluronan binding protein in several tissues of the proximal tibia. However, it does not appear to be the predominant hyaluronan binding protein in growing cartilages of the weanling rat.
Effects of combined knee loadings on posterior cruciate ligament force generation
Authors: Markolf Keith L. , Slauterbeck James L. , Armstrong Kevin L. , Shapiro Matthew M. , Finerman Gerald A. M. 
Published: February 2005

AbstractResultant forces in the posterior cruciate ligament were measured under paired combinations of posterior tibial force, internal and external tibial torque, and varus and valgus moment. The force generated in the ligament from a straight 100 N posterior tibial force was highly sensitive to the angle of knee flexion. For example, at 90 of flexion the mean resultant force in the posterior cruciate ligament was 112% of the applied posterior tibial force, whereas at 0°, only 16% of the applied posterior force was measured in the ligament. When the tibia was preloaded by 10 Nm of external torque, only 9–13% of the 100 N posterior tibial force was transmitted to the posterior cruciate ligament at flexion angles less than 60° at 90° of flexion, 61% was carried by the ligament. This “off‐loading” of the posterior cruciate ligament also occurred when the tibia was preloaded by 10 Nm or internal torque, but only at knee flexion angles between 20 and 40°. The addition of 10 Nm of valgus moment to a knee loaded by a 100 N posterior tibial force increased the mean force in the posterior cruciate ligament at all flexion angles except hyperextension: this represents a common and potentially dangerous loading combination. The addition of 10 Nm of varus moment to a knee loaded by a 100 N posterior tibial force increased the mean force in the posterior cruciate ligament at all flexion angles except hyperextension; this represents a common and potentially dangerous loading combination. The addition of 10 Nm of varus moment to a knee loaded by a 100 N posterior tibial force decreased the mean force in the ligament between 10 and 70° of flexion. External tibial torque (alone or combined with varus or valgus moment) was not an important loading mechanism in the posterior cruciate ligament. The application of internal torque plus varus moment at 90° of flexion produced the greatest posterior cruciate ligament forces in our study and represented the only potential injury mechanism that did not involve posterior tibial force.
SAS is amplified predominantly in surface osteosarcoma
Authors: Noble‐Topham S. E. , Kandel R. A. , Burrow S. R. , Bell R. S. , Eppert K. , Meltzer P. S. , Andrulis I. L. 
Published: February 2005

AbstractThe development of several types of human tumors is related to amplification of genes that are involved in cell growth. The protein products of these genes give the cells a selective growth advantage. The q13–15 region of chromosome 12 is frequently altered in human sarcomas, and the SAS gene has been identified in an amplification unit mapping to this region. Gene amplification of SAS was analyzed to determine the frequency of genetic alteration of this gene in osteosarcoma. Using Southern blot analysis as well as quantitative polymerase chain reaction. SAS was found to be amplified in 10 (36% ) of 28 osteosarcomas. Gene amplification was evaluated in subtypes of osteosarcoma. All seven surface osteosarcomas displayed amplified SAS. In contrast, SAS was amplified in only two (13% ) of 15 intramedullary osteosarcomas. The finding that all surface osteosarcomas demonstrated SAS gene amplification suggests that this gene may play a role in the pathogenesis of osteosarcoma subtypes and that surface osteosarcoma may be genetically different from high‐grade intramedullary osteosarcoma.
Signal pathways and ligament cell adhesiveness
Authors: Sung K‐L. Paul , Whittemore Darren E. , Yang Li , Amiel David , Akeson Wayne H. 
Published: February 2005

AbstractThe influence of signal pathways involved in the adhesion of fibroblasts from the anterior cruciate and medial collateral ligaments to fibronectin was investigated. Specific emphasis was paid to the cyclic adenosine monophosphate and Ca2+/phospholipid pathways to determine the signaling mediated by integrin receptors during cell binding and spreading on a fibronectin‐coated glass surface and to compare the roles of these two pathways in integrin‐mediated adhesion in fibroblasts from the two ligaments. Individual cell adhesion strengths were determined using a micropipette‐micromanipulation system after the cells were treated with signal pathway inhibiting agents. Adhesion in fibroblasts from the medial collateral ligament was significantly reduced by inhibiting agents for Gi protein, protein kinase A, protein kinase C, protein kinase G, phospholipase C, and calmodulin, which suggests a crucial role for cyclic adenosine monophosphate and Ca2+/phospholipid signaling in integrin‐mediated adhesion of these fibroblasts. Adhesion in fibroblasts from the anterior cruciate ligament, however, was reduced only by a protein kinase C inhibiting agent and was increased by inhibiting agents for protein kinase A, protein kinase G, and calmodulin, which suggests only a partial role of Ca2+/phospholipid signaling in integrin‐mediated adhesion of these fibroblasts. On the basis of additional parallel studies on the role of intracellular calcium in integrin‐mediated adhesion, medial collateral ligament and anterior cruciate ligament fibroblast adhesion was calcium dependent throughout the 60 minute time course of adhesion experiments. Fibroblasts from the medial collateral ligament demonstrated a 2.2‐fold increase in cytosolic free calcium upon binding to fibronectin, whereas fibroblasts from the anterior cruciate ligament demonstrated no significant increase in calcium. Overall, the study of the intrinsic differences between anterior cruciate ligament and medial collateral ligament fibroblasts in their signal pathways upon binding to fibronectin may reveal information important for further explaining the lack of functional healing response in the anterior cruciate ligament after injury.
Exponential model for the tensile true stress‐strain behavior of as‐irradiated and oxidatively degraded ultra high molecular weight polyethylene
Authors: Kurtz S. M. , Rimnac C. M. , Santner T. J. , Bartel D. L. 
Published: February 2005

AbstractFollowing sterilization by gamma radiation, ultra high molecular weight polyethylene components for total joint replacement undergo oxidative degradation upon exposure to air and the in vivo environment. Oxidative degradation is accompanied by an increase in density. The primary objective of this study was to develop a mathematical model to predict the monotonic tensile mechanical behavior of these sterilized components as a function of changes in density arising from oxidative degradation. Tensile specimens of ultra high molecular weight polyethylene were sterilized with gamma radiation and then oxidatively degraded in an air furnace. The average density of each specimen was measured using a density gradient column. Differential scanning calorimetry and Fourier transform infrared spectroscopy were conducted on selected specimens to characterize the physical and chemical changes due to accelerated aging as opposed to ambient shelf aging. Mechanical testing was conducted in monotonic uniaxial tension. An exponential model was fitted to the true stress‐strain data (up to a true strain of 0.12). The observed fitted stress had a correlation coefficient of 0.996. The model permits a quantitative prediction of the association between the true stress‐strain curve and density for the ultra high molecular weight polyethylene components. The proposed exponential model effectively describes changes in the large‐strain monotonic tensile behavior of as‐irradiated and oxidatively degraded ultra high molecular weight polyethylene components.
Altered load history affects periprosthetic bone loss following cementless total hip arthroplasty
Authors: Bryan J. M. , Sumner D. R. , Hurwitz D. E. , Tompkins G. S. , Andriacchi T. P. , Galante J. O. 
Published: February 2005

AbstractDual energy x‐ray absorptiometry was used to measure periprosthetic, distal femoral, and proximal tibial bone mass in the affected and contralateral limbs of eight patients 10 years after unilateral total hip arthroplasty with a cementless, porous‐coated titanium alloy femoral stem. Gait analyses to assess the presence of asymmetries in loading of the lower extremities were also performed 10 years postoperatively. The patients had excellent clinical results and no other significant lower extremity pathology. On the basis of comparison of the affected and unaffected proximal femora, bone loss adjacent to the proximal medial aspect of the femoral stem was determined to be 34% (p < 0.001). However, the patients also had 16% less bone in the ipsilateral proximal tibia (p = 0.003) and 15% less bone in the ipsilateral femur 3 cm distal to the prosthesis (p = 0.007) compared with the contralateral limb. When normalized to the asymmetry in tibial bone mineral content, the estimated proximal medial periprosthetic bone loss was still statistically significant, but the magnitude was reduced from 34 to 17% (p = 0.009). The gait analyses indicated that several measures that influence the loads at the hip and knee joints were reduced in the involved limb compared with the contralateral limb. Furthermore, the bilateral difference in the vertical component of the external force acting on the proximal tibia was correlated with the bilateral difference in tibial bone mineral content (r = 0.80, p = 0.02). These data suggest that two mechanical factors, the local stress‐shielding effect of the prosthesis and the global effect of decreased loading of the limb, can both make significant contributions to periprosthetic bone loss. It is apparent that the magnitude of the periprosthetic bone loss related to stress‐shielding has been overestimated by as much as 50% in retrospective studies.
In vitro measurement of strain in the bone cement surrounding the femoral component of total hip replacements during simulated gait and stair‐climbing
Authors: O'Connor Daniel O. , Burke Dennis W. , Jasty Murali , Sedlacek Ronald C. , Harris William H. 
Published: February 2005

AbstractThe strains in the cement mantle surrounding the cemented femoral component of a total hip replacement were measured in vitro, using strain gauges embedded within the cement mantle adjacent to the femoral component in femurs from cadavers under physiologic loads simulating both single‐limb stance and stair‐climbing. Cement strains in the most proximal portion of the cement mantle were measured with and without full contact of the collar of the femoral stem on the cortex of the medial portion of the femoral neck during both loading conditions. To our knowledge, these are the first studies to contrast by direct measurement the strain profile in the cement mantle of a cemented femoral component under simulated stair‐climbing with that occurring under simulated single‐limb stance. They extend the findings from finite element analyses and from clinical specimens retrieved at autopsy in identifying those regions of the cement mantle most likely to fail. At two specific foci, the magnitude of the strain in the cement mantle approaches values that could lead to early fatigue failure of the cement. The two regions in which the strains were highest (greater than 1,000 microstrain) were the most proximal portions of the cement mantle and near the tip of the femoral component. Although these two regions are recognized areas of high strain and also common sites of cement debonding and cement mantle failure, the strain‐gauge studies showed that the magnitude of cement strains in the proximal portion of the cement mantle were highest during stair‐climbing; in contrast, high strains at the tip region occurred in both gait and stair‐climbing. Contact between the collar and the medial portion of the femoral neck reduced the strain in the proximal portion of the cement mantle not only in single‐limb stance but in stair‐climbing as well. The level of strain recorded in these studies for a simulated person weighing 115 pounds (52 kg) could lead to cement fracture during extended in vivo service life of a cemented femoral component, from either single‐limb stance or stair‐climbing. This risk would be increased if a void or defect existed in the cement mantle at these sites. Moreover, the increase in strain in the cement mantle was linear with increases in body weight between 100 and 200 pounds (45 and 91 kg) of spinal load, indicating that strains in a heavy patient could readily exceed the fatigue limit of the cement, particularly if a stress riser such as a pore in the cement or a sharp corner of the prosthesis were present. These data reemphasize the need to continue efforts to develop methods to strengthen bone cement and to reduce those factors that increase the strain in the cement mantle of cemented femoral components of total hip arthroplasty, particularly proximally and near the tip.