bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical model for repair of fatigue damage and stress fracture in osteonal bone
Authors: Martin Bruce 
Published: February 2005

AbstractThis paper assembles current concepts about bone fatigue and osteonal remodeling into a mathematical theory of the repair of fatigue damage and the etiology of stress fracture. The model was used to address three questions. (a) How does the half‐life of fatigue damage compare with the duration of the remodeling cycle? (b) Does the porosity associated with the remodeling response contribute to stress fracture? (c) To what extent is a periosteal callus response necessary to augment repair by remodeling? To develop the theory, existing experimental data were used to formulate mathematical relationships between loading, damage, periosteal bone formation, osteonal remodeling, porosity, and elastic modulus. The resulting nonlinear relationships were numerically solved in an iterative fashion using a computer, and the behavior of the model was studied for various loading conditions and values of system parameters. The model adapted to increased loading by increasing remodeling to repair the additional damage and by adding new bone periosteally to reduce strain. However, if too much loading was encountered, the porosity associated with increased remodeling caused the system to become unstable: i.e., damage, porosity, and strain increased at a very high rate and without limit. It is proposed that this phenomenon is the equivalent of a stress fracture and that its biological and mechanical elements are significant in the etiology of stress fractures. Additional experiments must be done to test the model and provide better values for its parameters. However, the instability characteristic is relatively insensitive to changes in model parameters.
Modulation of cell phenotype in human osteoblast‐like cells by the simian virus 40
Authors: Evans Carol E. , Ng Kin , Allen Justine , Gallimore Phillip 
Published: February 2005

AbstractAt present, the majority of in vitro research into bone metabolism is performed on either primary cultures of bone or osteosarcoma lines. A better model of the behaviour of normal bone cells would be a cell line derived from normal, adult bone that retained osteoblast‐like characteristics. We infected a culture of bone cells from adult humans with simian virus 1613, a variant of the simian virus 40, and obtained 12 clones of variable morphology. The clones were maintained in culture for as long as 6 months. Population doubling times, synthesis of alkaline phosphatase and osteocalcin, secretion of mineral, morphology, and ability to withstand freezing were examined. SV/EC cell morphology varied from the polygonal, osteoblast‐like to the bipolar, fibroblast‐like. Population doubling times ranged from 0.55 to 2.8 days (compared with 3.9 days for the nontransformed human osteoblast‐like cells). Synthesis of alkaline phosphatase varied but was less than that by the human osteoblast‐like cells. With the exception of clone 11, all of the transformed clones synthesised mineral in vitro under mineralising conditions. Four clones showed increased synthesis of alkaline phosphatase and increased population doubling times after passaging. All of the clones were successfully frozen and thawed, but, unlike normal human osteoblast‐like cells, none responded to stimulation with parathyroid hormone. These results demonstrate that normal human bone cells can incorporate the simian virus 1613 while retaining some of their osteoblast‐like characteristics. Such manipulation affords these cells an extended lifespan, and this, together with their ability to withstand freezing, makes them a potentially useful tool in bone research.
Polymethylmethacrylate‐stimulated macrophages increase rat osteoclast precursor recruitment through their effect on osteoblasts in vitro
Authors: Pollice P. F. , Silverton S. F. , Horowitz S. M. 
Published: February 2005

AbstractAn in vitro rat osteoclast precursor model was employed to study the role of macrophages in the osteolysis associated with aseptic loosening of cemented total joint replacements. Bone resorption at the bone‐bone cement interface may involve the release of mediators by macrophages in response to phagocytosis of polymethylmethacrylate particles. Two potential pathways for the macrophage‐directed bone resorption were studied. An indirect pathway was investigated in which the macrophage response to cement particles was used to stimulate rat osteosarcoma (ROS) 17/2.8 osteoblasts. Osteoblast‐soluble factors then were added to osteoclast precursors. In the direct pathway, osteoclast precursors were exposed directly to macrophage‐soluble factors released in response to phagocytosis of cement particles. Osteoclast precursors were identified after adherence to polished human dentin slices. Acid phosphatase‐positive osteoclasts were counted using light microscopy at ×200 magnification. In the indirect pathway, where the macrophage response was mediated through the rat osteosarcoma osteoblasts, a significant increase in the recruitment of osteoclast precursors was observed. In the direct pathway, when the macrophage‐conditioned medium was allowed to interact directly with osteoclast precursors, the adherence of the precursors was significantly decreased. This demonstrates that the macrophage mediators released following phagocytosis of polymethylmethacrylate particles affect the release of soluble factors from osteoblasts. In turn, these osteoblast factors stimulate recruitment of osteoclast precursors to calcified tissue. Evidence from this in vitro model reveals that macrophage‐soluble factors, in the absence of an osteoblast contribution, decrease the adherence of osteoclast precursors to calcified substrate. We propose that bone resorption at the aseptically loose interface of cemented arthroplasty may be mediated, at least in part, by soluble factors secreted by osteoblasts responding to macrophages that have phagocytosed particles of polymethylmethacrylate cement.
Comparison of the effect of reamed and unreamed locked intramedullary nailing on blood flow in the callus and strength of union following fracture of the sheep tibia
Authors: Schemitsch E. H. , Kowalski M. J. , Swiontkowski M. F. , Harrington R. M. 
Published: February 2005

AbstractThis study was performed to compare the effects of reamed and unreamed locked intramedullary nailing on blood flow in the callus and early strength of union in a fractured sheep tibia model. After the creation of a standardized short spiral fracture by three‐point bending with torsion, each tibia was stabilized by the insertion of a locked intramedullary nail. Ten animals were allocated randomly into two groups: one that had reaming prior to nail insertion and one that did not. Blood flow was measured in real time with use of laser Doppler flowmetry. Endosteal perfusion was determined at the fracture site before and after nail insertion. Perfusion of the callus was measured at three locations (proximal diaphysis, fracture site, and distal diaphysis) and at three time intervals (2, 6, and 12 week follow‐up). All animals were killed 12 weeks postoperatively, and the tibiae were tested to failure in four‐point bending. Nailing with reaming resulted in a larger decrease in overall endosteal perfusion than nailing without reaming (p < 0.015). The presence or absence of reaming did not affect blood flow within fracture callus. Perfusion of callus was greatest at 6 weeks of follow‐up. Bending strength and stiffness were the same in both groups at 12 weeks. The study demonstrated that perfusion of callus and early strength of union are similar following intramedullary nailing with or without reaming.
Synergistic effect of growth factors on cell outgrowth from explants of rabbit anterior cruciate and medial collateral ligaments
Authors: Lee Joe , Green Melvin H. , Amiel David 
Published: February 2005

AbstractCellular migration and proliferation are integral aspects of wound healing. An in vitro assay for cellular migration and proliferation using explants of rabbit anterior cruciate and medial collateral ligaments was developed previously. This study presents the effects of serum‐free culture medium supplemented with basic fibroblast growth factor, bovine insulin, transforming growth factor‐β1, and platelet‐derived growth factor‐B, added either individually or in combination, on cell outgrowth in explants of rabbit anterior cruciate and medial collateral ligaments. Outgrowth was assessed at 3 and 6 days by counting the number of cells surrounding the tissue explants. For explants of both ligaments, cell outgrowth was dependent on the presence of 10% fetal bovine serum or the combination of growth factors. Little outgrowth occurred in explants of either ligament in the presence of basic fibroblast growth factor, transforming growth factor‐β1, or bovine insulin. Platelet‐derived growth factor‐B at concentrations of 20 and 100 ng/ml seemed to increase cell outgrowth from medial collateral ligament explants at 6 days. The outgrowth from the explants of both ligaments was much greater in the presence of all four growth factors than the sum of the outgrowth with the individual factors. This synergistic effect was as much as 10‐fold and 20‐fold for the anterior cruciate ligament explants at days 3 and 6, respectively, but no more than 3‐fold for the medial collateral ligament explants at these times. Medial collateral ligament explants exhibited greater cell outgrowth than anterior cruciate ligament explants in 10% serum and in the presence of the four growth factors.
Mechanical behavior of articular cartilage in shear is altered by transection of the anterior cruciate ligament
Authors: Setton L. A. , Mow V. C. , Howell D. S. 
Published: February 2005

AbstractThe flow‐independent viscoelastic and equilibrium behaviors of canine articular cartilage were examined with time after transection of the anterior cruciate ligament. The equilibrium, transient, and dynamic shear behaviors of cartilage were studied in biaxial compression‐torsion testing at two time periods after transection of the anterior cruciate ligament and at two sites on the femoral condyle, in order to test for differences between sites of frequent and less frequent contact. Water content also was measured in cartilage at sites corresponding to the areas of mechanical testing. Transection of the anterior cruciate ligament produced significant decreases in all measured moduli of articular cartilage tested in equilibrium and dynamic shear and in equilibrium compression; the values for these moduli were 61, 56, and 77% of the control values, respectively, beginning at 6 weeks following transection of the anterior cruciate ligament. There was evidence of increased energy dissipation of cartilage in shear, with a 13 and 35% increase in tan δ at 6 and 12 weeks after transection of the anterior cruciate ligament, respectively. Changes in the viscoelastic relaxation function of cartilage in shear also were evident at 12 weeks after surgery. In all tissue, there was a significant increase in hydration of approximately 4% at 6 or 12 weeks after surgery. There was little difference between the material parameters for areas considered to be in frequent and less frequent contact, with the exception of hydration, which was greater for areas of less frequent contact. The observed changes in material properties demonstrate that relatively short periods of joint instability result in significant changes in the flow‐independent viscoelastic behavior of articular cartilage, as well as in the intrinsic stiffnesses in compression and shear.
Effects of excimer laser on healing of articular cartilage in rabbits
Authors: Athanasiou K. A. , Fischer R. , Niederauer G. G. , Puhl W. 
Published: February 2005

AbstractThis study examined healing of 1.0 mm diameter defects in rabbit knee articular cartilage for as long as 14 weeks after creation of the defects by either laser or drilling. The purpose of the research was to determine the effects of laser debridement of cartilage on the intrinsic biomechanical properties of the repair tissue. We therefore imitated chondral shaving and subchondral abrasion of cartilage by creating partial‐thickness and full‐thickness cartilage defects of standardized size with both excimer laser and drilling. Light and scanning electron microscopic examinations of the repair tissue showed that healing of osteochondral defects created by laser may be delayed compared with defects created by drilling, for at least 6 weeks postoperatively. Even though there initially was a considerable delay in healing in the laser group, neither laser nor drilling had any appreciable effects on the mechanical properties of the repair tissue, as demonstrated by biomechanical testing at 14 weeks. Specifically, the repair cartilage in the defects in the laser group had the following material properties (mean ± SD): aggregate modulus, 0.40 ± 0.24 MPa; Poisson's ratio, 0.37 ± 0.08; permeability, 3.72 ± 4.28 × 10−15 m4/N.s; and thickness, 0.20 ± 0.06 mm. The corresponding values for the defects in the drilling group were 0.39 ± 0.23 MPa, 0.34 ± 0.09, 3.82 ± 3.44 × 10−15 m4/N.s, and 0.22 ± 0.09 mm. The repair tissue from both types of defects was pooled, and the values were compared with those for contralateral (control) tissue. The control tissue had a 51% greater aggregate modulus (0.59 ± 0.18 MPa, p = 0.0001), 34% less Poisson's ration (0.23 ± 0.25, p = 0.0001), 48% less permeability (1.94 ± 0.96 × 10−15 m4/N.s, p = 0.0001), and was 29% thicker (0.27 ± 0.08 mm, p = 0.0001). Thus, as evidenced by biomechanical testing at 14 weeks, neocartilage in both superficial and osteochondral defects, created by either laser or a drill, exhibited structural integrity inferior to that of normal control tissue.
Biomechanics of patellar tendon autograft for reconstruction of the anterior cruciate ligament in the goat: Three‐year study
Authors: Ng Gabriel Y. , Oakes Barry W. , Deacon Owen W. , McLean Iain D. , Lampard Douglas 
Published: February 2005

AbstractThis study examined the biomechanics of anterior cruciate ligament‐patellar tendon autografts for as long as 3 years after surgery. Twenty‐seven adult female goats were tested; four served as controls and the others received an autograft to the right knee with each left knee serving as an additional control. The animals with grafts were tested at 0 week (n = 4), 6 weeks (n = 4), 12 weeks (n = 4), 24 weeks (n = 3), 1 year (n = 5), and 3 years (n = 3) after surgery. The anteroposterior laxity of the knee joint, load‐relaxation, and structural and material properties of the graft were tested. The anteroposterior laxity was significantly greater than that of the controls for all groups except at 3 years. Load‐relaxation was greater than that of the control anterior cruciate ligaments, but in the 1 and 3‐year grafts load‐relaxation was less than that of the patellar tendons with 5 minutes of sustained loading. Between 12 and 52 weeks, the stiffness and modulus of the grafts increased 3‐fold, but the improvement was slow afterward. At 3 years, the strength and stiffness of the grafts were 44 and 49% those of the control ligaments, respectively; the modulus was 37 and 46% that of the control anterior cruciate ligaments and patellar tendons, respectively. The persistent inferior mechanical performance at 3 years suggests that anterior cruciate ligament grafts may never attain normal strength.
Comparison of the type‐2 insulin‐like growth factor receptor in normal osteoblasts and osteosarcoma‐derived osteoblast‐like cells
Authors: Ishibe M. , Nojima T. , Ishibashi T. , Koda T. , Rosier R. N. , Puzas J. E. , Kaneda K. 
Published: February 2005

AbstractInsulin‐like growth factor‐II is known to stimulate the proliferation and differentiation of osteoblasts in part through activation of the type‐2 insulin‐like growth factor receptor. The present study examined the type‐2 insulin‐like growth factor receptors of three normal osteoblast‐like cells and three osteosarcoma‐derived osteoblast‐like cells (OGA, SU, and IMAI) from humans. [125I]insulin‐like growth factor‐II was used for the binding studies. All of the cell types had high affinity binding sites for insulin‐like growth factor‐II (dissociation constants [Kd] ⩽ 1 nM). The concentration of these sites was 10 to 24‐fold higher in normal osteoblasts than in the osteosarcoma cells studied. Unlabeled insulin‐like growth factor‐II inhibited the binding of [125I]insulin‐like growth factor‐II to the cells in a dose‐dependent manner; however, unlabeled insulin‐like growth factor‐I and insulin were less effective. Covalent crosslinking of insulin‐like growth factor‐II binding sites gave molecular mass estimates of Mr 250,000 in human osteoblast cells, 250,000 and 130,000 in OGA cells. 240,000 in SU cells, and 250,000 and 130,000 in IMAI cells. Unlabeled insulin‐like growth factor‐II inhibited all affinity labeling. In Northern blot analysis, the type‐2 insulin‐like growth factor receptor mRNA of normal osteoblasts was seen in greater abundance than it was in osteosarcoma cells. These results indicate that the numbers of type‐2 insulin‐like growth factor receptors differ between normal and transformed osteoblasts and that the differential expression of the receptor may be due to the differentiation of osteoblasts.
De novo synthesis of type‐I collagen in bone biopsy material
Authors: Röcher W. , Hostert E. , Dietz G. , Bartholmes P. 
Published: February 2005

AbstractA simple and rapid method was established for the cultivation of bone cell tissue. Human bone tissue derived from orthopaedic surgery was cultivated in the presence of 14C‐proline and β‐aminopropionitrile. De novo synthesized collagen was extracted from the tissue and quantified by determination of radioactivity in the purified protein. Measurements of the oxygen consumption of the tissue provided evidence that the physiological conditions for the tissue were optimal. The tissue was vital over a period of as long as 7 days, showing normal respiration and a constant rate of collagen synthesis. The observed levels of alkaline phosphatase and acid phosphatase activity clearly demonstrated that mainly osteoblasts were involved in metabolic activity. The described system is suitable for investigations of bone cell metabolism under quasiphysiological conditions.
Involvement of platelets in stimulating osteogenic activity
Authors: Slater Michael , Patava John , Kingham Karen , Mason Rebecca S. 
Published: February 2005

AbstractOsteoblast‐like cells have been shown to be sensitive to the proliferative action of a wide variety of growth factors. Many of these growth factors have been isolated from platelets and are thought to be released at local sites in response to injury. In this study, we tested whether human platelet concentrate, as a supplement to basic medium, would support the proliferative and functional activity of human fetal osteoblast‐like cells in both short‐term and long‐term culture. In short‐term studies, uptake of [3H]thymidine was increased in platelet‐treated cultures by more than 4‐fold compared with 10% serum‐supplemented controls. When cultured for prolonged periods on coverslips, the cells formed multilayers, with a collagen‐based matrix separating the layers. Long‐term cultures that were treated with 1.5% (vol/vol) platelets in serum‐supplemented medium showed increases in the depth of the multilayers of as much as 36‐fold at 30 days after confluence, compared with the 10% serum‐supplemented controls; this difference persisted until day 50. Incorporation of growth factor in the matrix was examined with the use of colloidal gold immunoelectron microscopy. Immunogold labeling intensities for transforming growth factor‐β1 were significantly lower in the platelet‐treated cultures at 20 days and then increased to a maximum level of 2.1‐fold more than in the controls at 40 days. Labeling intensities for insulin‐like growth factor‐I and basic fibroblast growth factor were significantly lower in the platelet‐treated cultures than in the controls at all stages of culture. These results indicate that platelet‐supplemented medium stimulates proliferation and maintains the differentiated function of human osteoblast‐like cells. Platelets may play an important role in early healing of fractures and also may be useful as a cheap autologous source of multiple growth factors to enhance osteoblast proliferation in vivo and in vitro.
Uniformity of resorptive bone loss induced by disuse
Authors: Gross Ted S. , Rubin Clinton T. 
Published: February 2005

AbstractStrains induced in the skeleton by functional activity are critical to the homeostasis of bone tissue. An in vivo model of disues osteopenia was used to examine whether the removal of these regulatory stimuli induces a uniform loss of crotical bone through the whole organ or whether the loss of bone is focused at specific sites of the cortex. The right radii of five adult male turkeys were isolated from their normal functional loading for 8 weeks. The corresponding left radius from each animal served as an intact contralateral control. An additional group of five turkeys was used as time‐zero controls to assess the initial areal symmetry of the left and right radii. Areal properties were assessed at three sites at equal intervals spanning the middle 3 cm of the diaphysis. Adaptation was determined for each cross section as a whole, as well as specifically by site by division of each cross section into 12 equal angle sectors. The average across all experimental sections after 8 weeks of disuse was 12.1 ± 1.9% (± SE) loss of bone mass. The change in mean cross‐sectional area varied little between the three diaphyseal sites (−10.2 ± 3.3%, −13.5 ± 3.8%, and −12.6 ± 4.0%) and occurred primarily (84%) by uniform expansion of the endosteal envelope. However, elevated intracortical porosity following 8 weeks of disuse was highly nonuniform, with 58% of the increased porosity preferentially located in the ventral/caudal cortex (representing only 25% of the cortical area). From these data, it is concluded that bone responds to the removal of functional stimuli with a uniform, organ‐wide loss of mass, yet intracortical remodeling occurs preferentially within specific areas of the cortex. The lack of spatial coupling between these events suggests that the two processes may be governed by distinct physiologic criteria.
Evaluation of influence of 24‐hour cold preservation on endothelin production and on endothelin receptors in the bone vasculature
Authors: Coessens Bruno C. , Adams Mary L. , Wood Michael B. 
Published: February 2005

AbstractEndothelin‐1 is a vasoactive peptide produced by the vascular endothelium. It is one of the most potent endogenous vascular smooth muscle constrictors. Two subtypes of the endothelin receptor have been cloned and sequenced and denoted endothelin‐A and endothelin‐B. The aim of this study was to define the influence of cold ischemia on the production of endothelin‐1 and on the endothelin receptors. Two different preservation techniques (cold storage only and cold storage with microperfusion with University of Wisconsin solution) also were compared. The study was performed in an in vitro bone perfusion model to isolate the vascular endothelium from blood components. The production of endothelin‐1 by the bone vasculature was not altered after 24 hours of cold ischemia. No contractions were observed with S6c, a selective endothelin‐B agonist, and this effect was not influenced by cold ischemia. The response mediated by the endothelin‐A receptor was increased significantly, an effect that was not influenced by preservation with University of Wisconsin solution. This latter finding was the only significant alteration in the vascular function detected in the in vitro model after 24 hours of cold ischemia. With regard to the pharmacologic properties of endothelin‐1, this mediated response could be implicated in the pathogenesis of vasospasm.