bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulsed electromagnetic field stimulation of MG63 osteoblast‐like cells affects differentiation and local factor production
Authors: Lohmann C. H. , Schwartz Z. , Liu Y. , Guerkov H. , Dean D. D. , Simon B. , Boyan B. D. 
Published: February 2005

AbstractPulsed electromagnetic field stimulation has been used to promote the healing of chronic nonunions and fractures with delayed healing, but relatively little is known about its effects on osteogenic cells or the mechanisms involved. The purpose of this study was to examine the response of osteoblast‐like cells to a pulsed electromagnetic field signal used clinically and to determine if the signal modulates the production of autocrine factors associated with differentiation. Confluent cultures of MG63 human osteoblast‐like cells were placed between Helmholtz coils and exposed to a pulsed electromagnetic signal consisting of a burst of 20 pulses repeating at 15 Hz for 8 hours per day for 1, 2, or 4 days. Controls were cultured under identical conditions, but no signal was applied. Treated and control cultures were alternated between two comparable incubators and, therefore, between active coils; measurement of the temperature of the incubators and the culture medium indicated that application of the signal did not generate heat above the level found in the control incubator or culture medium. The pulsed electromagnetic signal caused a reduction in cell proliferation on the basis of cell number and [3H]thymidine incorporation. Cellular alkaline phosphatase‐specific activity increased in the cultures exposed to the signal, with maximum effects at day 1. In contrast, enzyme activity in the cell‐layer lysates, which included alkaline phosphatase‐enriched extracellular matrix vesicles, continued to increase with the time of exposure to the signal. After 1 and 2 days of exposure, collagen synthesis and osteocalcin production were greater than in the control cultures. Prostaglandin E2 in the treated cultures was significantly reduced at 1 and 2 days, whereas transforming growth factor‐β1 was increased; at 4 days of treatment, however, the levels of both local factors were similar to those in the controls. The results indicate enhanced differentiation as the net effect of pulsed electromagnetic fields on osteoblasts, as evidenced by decreased proliferation and increased alkaline phosphatase‐specific activity, osteocalcin synthesis, and collagen production. Pulsed electromagnetic field stimulation appears to promote the production of matrix vesicles on the basis of higher levels of alkaline phosphatase at 4 days in the cell layers than in the isolated cells, commensurate with osteogenic differentiation in response to transforming growth factor‐β1. The results indicate that osteoblasts are sensitive to pulsed electromagnetic field stimulation, which alters cell activity through changes in local factor production.
Biomechanical consequences of an isolated overload on the human vertebral body
Authors: Kopperdahl David L. , Pearlman Jonathan L. , Keaveny Tony M. 
Published: February 2005

AbstractThe biomechanical consequences of an isolated overload to the vertebral body may play a role in the etiology of vertebral fracture. In this context, we quantified residual strains and reductions in stiffness and ultimate load when vertebral bodies were loaded to various levels beyond the elastic regimen and related these properties to the externally applied strain and bone density. Twenty‐three vertebral bodies (T11‐L4, from 23 cadavers aged 20–90 years) were loaded once in compression to a randomized nominal strain level between 0.37 and 4.5%, unloaded, and then reloaded to 10% strain. Residual strains of up to 1.36% developed on unloading and depended on the applied strain (r2 = 0.85) but not on density (p = 0.25). Percentage reductions in stiffness and ultimate load of up to 83.7 and 52.5%, respectively, depended on both applied strain (r2 = 0.90 and r2 = 0.32, respectively) and density (r2 = 0.23 and r2 = 0.22, respectively). Development of residual strains is indicative of permanent deformations, whereas percentage reductions in stiffness are direct measures of effective mechanical damage. These results therefore demonstrate that substantial mechanical damage—which is not visible from radiographs—can develop in the vertebral body after isolated overloads, as well as subtle but significant permanent deformations. This behavior is similar to that observed previously for cylindrical cores of trabecular bone. Taken together, these findings indicate that the damage behavior of the lumbar and lower thoracic vertebral body is dominated by the trabecular bone and may be an important factor in the etiology of vertebral fracture.
Efficacy of monitoring long‐bone fracture healing by measurement of either bone stiffness or resonant frequency: Numerical simulation
Authors: Roberts Sydney G. , Steele Charles R. 
Published: February 2005

AbstractDevelopment of noninvasive mechanical tests to monitor fracture healing has been hindered because relationships between bone geometry, measurement conditions, and fracture callus strength are not well understood. Beam theory was used to analyze the effects of fracture length, fracture location, end conditions, and fracture callus stiffness on mechanical properties (resonant frequency, bending stiffness, and torsional stiffness) of healing bone. Actual bone mineral geometry from a human tibia, quantified every 1 mm, was used in the beam analysis. Geometry of the fracture callus segment was uniformly scaled from the values for intact bone. Experimental tests on multisegmented machined rods were used to verify analytical methods. Mechanical properties of the healing bone initially increased very rapidly to 30–70% of the stiffness of intact bone, depending on the configuration. The increases then tapered off dramatically. Lateral bending stiffness was sensitive to changes in callus properties for a larger portion of the healing process than was either torsional stiffness or resonant frequency. Because callus strength increases at half the rate of callus stiffness, measures of whole‐bone mechanical properties can provide insight into changes in callus strength until a maximum of less than one‐half the strength of intact bone is regained. The analytical method presented is proposed for clinical use to develop individualized models of bone, fracture, and fixation conditions to identify early stages of healing. Because increases in whole‐bone mechanical properties are small in the later stages of fracture healing, however, such measures must be used prudently beyond the initial stages.
Vascular proliferation and blood supply during distraction osteogenesis: A scanning electron microscopic observation
Authors: Choi In Ho , Ahn Jae Hoon , Chung Chin Youb , Cho Tae‐Joon 
Published: February 2005

AbstractThis scanning electron microscopic study examined the spatial and temporal features of proliferating vessels of regenerating bone tissue and blood supply during distraction osteogenesis. A rat model of tibial lengthening was used with a protocol divided into a latency period of 7 days, a distraction period that lasted 14 days with a daily distraction rate of 0.5 mm on two steps, and a consolidation period of 21 days. Vascular casting was done on the hindlimbs before osteotomy and on postoperative days 7, 14, 21, 28, and 42. Scanning electron microscopic findings were correlated with radiological and histological observations. On days 7 and 14, the proliferation of periosteal vessels was pronounced and there was distinct subperiosteal bone formation on the osteotomized surfaces. On day 2, vascular branches from the medullary canal of the host bone formed a vascular network, which gave rise to multiple axial, straight vascular branches, running parallel to the direction of distraction, toward the interzone, in accordance with the progress of mineralization. On day 28, the periosteum provided vascularization to the peripheral side of the interzone whereas the center of the interzone was still relatively avascular. On day 42, the periosteal and medullary vascular channels were completely connected at the distraction site including the interzone, which was occupied by developing and mature bone trabeculae. These results suggest that vascular proliferation occurs actively during the latency and distraction periods and then gradually decreases over time. A close temporal and spatial relationship exists between formation of regenerated bone and vascular proliferation of the periosteum and medullary canal.
Markers of joint tissue turnover in joint fluids from hips with osteonecrosis of the femoral head
Authors: Jingushi Seiya , Lohmander L. Stefan , Shinmei Masayuki , Hoerrner Lori A. , Lark Michael W. , Sugioka Yoichi , Iwamoto Yukihide 
Published: February 2005

AbstractOsteonecrosis of the femoral head often results in secondary osteoarthritis of the hip joint; however, the pathologic processes underlying the destruction of articular cartilage are not fully understood. Molecular markers in the hip joint fluids were measured to examine the changes in turnover of cartilage and other joint tissues. Marker data were related to clinical, radiological, and histopathological changes in the articular cartilage of the hip. Forty‐five patients (median age: 43 years) were studied. The median time between the onset of symptoms and sampling of hip synovial fluid was 6 months. Aggrecan fragments, C‐propeptide of type‐II collagen, matrix metalloproteinase‐3, and tissue inhibitor of metalloproteinases‐1 levels in joint fluid were determined by immunoassay. Osteonecrosis of the femoral head was graded by radiology as minimal collapse of the femoral head (stage 2: 26 patients), severe collapse (stage 3: 15 patients), or severe collapse with osteoarthritis (stage 4: four patients). Histologica changes of the articular cartilage, consistent with early‐stage osteoarthritis, were evident at stage 3 and were more advanced at stage 4. The average concentrations of proteoglycan fragments and C‐propeptide of type‐II collagen were 207 (SD 182) μg/ml and 19.6 (SD 19.3) ng/ml, respectively. The average concentrations of matrix metalloproteinase‐3 and tissue inhibitor of metalloproteinases‐ 1 were 177 (SD 291) nM and 23.0 (SD 9.9) nM, respectively. Measurable levels for all markers assayed were noted in the earliest stage of the disease, only a few months after the onset of symptoms and well before the appearance of radiological changes. Levels of matrix metalloproteinase‐3 and molar ratios of matrix metalloproteinase‐3/tissue inhibitor of metalloproteinases‐1 were higher in early stage disease than in later stage disease.
Changes in cross‐sectional geometry of the distal femoral metaphysis associated with inflammatory arthritis are reduced by a bisphosphonate (zoledronate)
Authors: Pysklywec Michael W. , Moran Erica L. , Bogoch Earl R. 
Published: February 2005

AbstractAn increased risk of fracture is a feature of rheumatoid arthritis and of animal models of inflammatory arthritis. We examined geometrical changes in the metaphyseal cortex of the distal femur in an animal model of inflammatory arthritis. Additionally, we examined the effect of a bisphosphonate in preventing these changes. Five groups of rabbits were studies: normal controls, those with inflammatory arthritis, and three groups with arthritis treated with bisphosphonate. To determine geometrical properties, image analysis was performed on digitized cross sections of the femoral metaphyseal cortices. The results demonstrated that the posterior cortical wall was significantly less thick in rabbits with arthrits than in normal rabbits and in the rabbits in the three bisphosphonate treatment groups (p < 0.05). Moment of inertia about the lateral‐medial axis was reduced inrabbits with arthritis compared with normal rabbits (p < 0.05). Cross‐sectional area was not significantly different between groups. The changes suggest a mechanism of weakening of bone in arthritis; when the results are coupled with results of previous porosity studies, severe directional weakness is apparent. Bisphosphonate was effective in preserving bone integrity in inflammatory arthritis.
Quantitative assessment of the effect of 0.05% chlorhexidine on rat articular cartilage metabolismin vitroandIn vivo
Authors: Reading A. D. , Rooney P. , Taylor G. J. S. 
Published: February 2005

AbstractWound infection remains a problem. Syringe and needle jet lavage of chlorhexidine gluconate 0.05% removed or killed 99.8% of contaminating bacteria within 1 minute in a wound model. In clinical use, however, possibletoxicity to articular cartilage is a concern. In an established intact rat patella modelin vitro, 1 minute of exposure to chlorhexidine 0.05% and chlorhexidine jet lavage did not significantly alter cartilage metabolism. A 1‐hour exposure decreased metabolic activity.In vivo, a 30‐minute exposure with or without rinsing produced no impairment of metabolic activity 6 weeks later, suggesting that cartilage has the potential for biological recovery. However, injecting and leaving chlorhexidine 0.05% in the joints was detrimental to the metabolic activity of the articular cartilage as assessed 6 weeks later. Thus, chlorhexidine gluconate 0.05% could be used on normal articular cartilage. Any potential damage from prolonged exposure can be avoided by rinsing after 1 minute.
Nitric oxide as a mediator of nucleus pulposus‐induced effects on spinal nerve roots
Authors: Brisby Helena , Byröd Gunnar , Olmarker Kjell , Miller Virginia M. , Aoki Yoshihito , Rydevik Björn 
Published: February 2005

AbstractNerve root dysfunction and sciatic pain in disc herniation are considered to be caused by mechanical compression and related to the presence of nucleus pulposus in the epidural space. Autologous nucleus pulposus has been shown to induce endoneural edema and to decrease nerve‐conduction velocity in spinal nerve roots in experimental disc herniation models, and inflammatory mediators have been suggested to be involved in these mechanisms. Nitric oxide, a potent inflammatory mediator, is implicated in vasoregulation, neurotransmission, and neuropathic pain. Nitric oxide synthesis can be induced by different cytokines, e.g., tumor necrosis factor‐α, which recently was shown to be of pathophysiological importance in experimental disc herniation. The enzyme nitric oxide synthase mediates the production of nitric oxide. Three series of experiments were performed in rat and pig disc herniation models to (a) investigate nitric oxide synthase activity in spinal nerve roots after exposure to autologous nucleus pulposus and (b) evaluate the effects of systemic treatment with aminoguanidine, a nitric oxide synthase inhibitor, on vascular permeability and nerve‐conduction velocity. In a disc herniation model in the rat, calcium‐independent nitric oxide synthase activity was measured in nerve roots exposed to nucleus pulposus; however, no nitric oxide synthase activity was detected in nerve roots from animals that underwent a sham operation, reflecting increased inducible nitric oxide synthase activity. In nucleus pulposus‐exposed spinal nerve roots in the pig, the edema was less severe after systemic aminoguanidine administration than without aminoguanidine treatment. Aminoguanidine treatment also significantly reduced the negative effect of nucleus pulposus on nerve‐conduction velocity in spinal nerve roots in the pig. These results demonstrate that nucleus pulposus increases inducible nitric oxide synthase activity in spinal nerve roots and that nitric oxide synthase inhibition reduces nucleus pulposus‐induced edema and prevents reduction of nerve‐conduction velocity. Furthermore, the results suggest that nitric oxide is involved in the pathophysiological effects of nucleus pulposus in disc herniation.
Pamidronate prevents bone loss associated with carrageenan arthritis by reducing resorptive activity but not recruitment of osteoclasts
Authors: Moran Erica L. , Fornasier Victor L. , Bogoch Earl R. 
Published: February 2005

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 water ad libitum from 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 arthritis.
Viscoelastic properties of chondrocytes from normal and osteoarthritic human cartilage
Authors: Trickey Wendy R. , Lee Greta M. , Guilak Farshid 
Published: February 2005

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 osteoarthritic cartilage.
Osteoprotegerin inhibits tumor‐induced osteoclastogenesis and bone tumor growth in osteopetrotic mice
Authors: Clohisy Denis R. , Ramnaraine Margaret L. , Scully Sheila , Qi Meiying , Van Gwyneth , Tan Hong Lin , Lacey David L. 
Published: February 2005

AbstractOsteoprotegerin and osteoprotegerin ligand have recently been identified as novel proteins that inhibit and stimulate, respectively, osteoclast formation. We examined the possibility that osteoprotegerin would inhibit cancer‐induced osteoclastogenesis and cancer growth in bone. An experimental model was used in which osteolytic tumors are known to stimulate osteoclastogenesis and grow in femora of osteoclast‐deficient mice (op/op). Osteoprotegerin treatment decreased the number of osteoclasts by 90% (p < 0.0007) at sites of tumor in a dose‐dependent manner and decreased bone tumor area by greater than 90% (p < 0.003). The mechanisms through which osteoprotegerin decreased osteoclast formation in tumor‐bearing animals included (a) an osteoprotegerin‐mediated, systemic reduction in the number of splenic and bone marrow‐residing osteoclast precursor cells. (b) a decrease in the number of osteoclast precursor cells at sites of tumor as detected by cathepsin K and receptor activator of NFkB mRNA expression, and (c) a decrease in osteoprotegerin ligand mRNA at sites of tumor. These findings suggest that osteoprotegerin treatment, in addition to having direct antagonistic effects on endogenous osteoprotegerin ligand, decreases the number of osteoclast precursors and reduces production of osteoprotegerin ligand at sites of osteolytic tumor.
Reinsertion of stimulated nucleus pulposus cells retards intervertebral disc degeneration: An in vitro and in vivo experimental study
Authors: Okuma Masahiko , Mochida Joji , Nishimura Kazuhiro , Sakabe Kou , Seiki Kanji 
Published: February 2005

AbstractReinsertion of autogenous nucleus pulposus, an innovative method to delay further disc degeneration, has been proved with an experimental animal model. This study examined whether coculture of nucleus pulposus cells with annulus fibrosus cells (a) activates annulus fibrosus cells and (b) retards disc degeneration when reinserted into the disc in a rabbit model of disc degeneration. Coculture of the two cell types stimulated proliferation of each, as indicated by increased DNA synthesis measured by increases in DNA polymerase α expression and uptake of 5‐bromo‐2 deoxy‐uridine assessed by an enzyme‐linked immunosorbent assay. In a model of disc degeneration in rabbits, reinsertion of activated nucleus pulposus cells delayed the formation of clusters of chondrocyte‐like cells, the destruction of disc architecture, and the elaboration of type‐II collagen as measured immunohistochemically compared with no treatment. The direct reinsertion of activated nucleus pulposus cells into the disc offers a promising line of investigation for delaying intervertebral disc degeneration, although these results obtained with notochordal cells may not necessarily apply when mature central nucleus pulposus cells are used.