bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation by IGF‐I and TGF‐β1 of swarm‐rat chondrosarcoma chondrocytes
Authors: Matsumura Takashi , Whelan Mary C. , Li Xiao Q. , Trippel Stephen B. 
Published: February 2005

AbstractThe growth factors transforming growth factor‐beta 1 and insulin‐like growth factor‐I influence a wide range of cellular actions, including the growth of several neoplastic cell types. Their role in the regulation of neoplastic chondrocytes remains unclear. We tested the hypotheses that transforming growth factor‐beta 1 and insulin‐like growth factor‐I differentially regulate neoplastic chondrocytes and interact to modulate the mitotic and matrix synthetic activities of neoplastic chondrocytes. We used Swarm‐rat chondrosarcoma chondrocytes to investigate the effect of each factor individually and of both factors in combination on [3H]thymidine incorporation into DNA and on [35S]sulfate incorporation into glycosaminoglycans. Each factor increased [3H]thymidine incorporation 2.7‐fold; transforming growth factor‐beta 1 achieved this effect at a 20‐fold lower concentration than insulin‐like growth factor‐I. In contrast, insulin‐like growth factor‐I stimulated [35S]sulfate incorporation 3.5‐fold; this was twice the maximal effect of transforming growth factor‐beta 1. Transforming growth factor‐beta 1 and insulin‐like growth factor‐I each decreased the proportion of newly synthesized glycosaminoglycans that were retained in the cells and pericellular matrix, indicating that the anabolic effect of these factors is only partly directed toward cell‐associated matrix production. The mitogenic and matrix synthetic actions of insulin‐like growth factor‐I and transforming growth factor‐beta 1 were synergistic. In concert, they increased [3H]thymidine incorporation approximately 12‐fold, an effect three times greater than the sum of the maximal stimulation achieved by each factor individually. Similarly, transforming growth factor‐beta 1 and insulin‐like growth factor‐I together increased glycosaminoglycan synthesis approximately two times more than the sum of their maximal individual effects. Taken together, these data indicate that these chondrosarcoma chondrocytes are positively regulated by insulin‐like growth factor‐I and transforming growth factor‐beta 1 and that these growth factors interact to augment the mitotic and matrix synthetic actions of the chondrocytes. If supported in human models, the sensitivity to growth factors of these cells suggests that interventions directed toward growth factor inhibition may be of therapeutic value.
Simultaneous changes in the mechanical properties, quantitative collagen organization, and proteoglycan concentration of articular cartilage following canine meniscectomy
Authors: LeRoux Michelle A. , Arokoski Jari , Vail T. Parker , Guilak Farshid , Hyttinen Mika M. , Kiviranta Ilkka , Setton Lori A. 
Published: February 2005

AbstractThe mechanical properties and microstructure of articular cartilage from the canine tibial plateau were studied 12 weeks after total medial meniscectomy. The organization of the birefringent collagen network was measured with quantitative polarized light microscopy to determine the thickness and the degree of organization of the superficial and deep zones. The zonal concentration of sulfated glycosaminoglycan was quantified with digital densitometry of safranin‐O staining. Equilibrium compressive and shear properties, as well as dynamic shear properties, were measured at sites adjacent to those of microstructural analysis. The results evinced significant loss of cartilage function following meniscectomy, with decreases of 20–50% in the compressive and shear moduli. There was no evidence of alterations in the degree of collagen fibrillar organization, although a complete loss of the surface zone was seen in 60% of the samples that underwent meniscectomy. Meniscectomy resulted in a decreased concentration of sulfated glycosaminoglycan, and significant positive correlations were found between the equilibrium compressive modulus and the glycosaminoglycan content. Furthermore, the shear properties of cartilage correlated directly with collagen fibrillar organization measured at the superficial zone of corresponding sites. These findings demonstrate that meniscectomy leads to impaired mechanical function of articular cartilage, with significant evidence of quantitative correlations between cartilage microstructure and mechanics.
Pressure‐induced periprosthetic osteolysis: A rat model
Authors: Skripitz Ralf , Aspenberg Per 
Published: February 2005

AbstractRecent animal experiments have indicated that oscillating fluid pressure at the interface of bone and implant can lead to osteolysis. However, external nonphysiologic saline solutions were used to generate the pressure in these studies. In the present study on 15 Sprague‐Dawley rats, hydrostatic pressure fluctuations were applied to bone through body fluids, by compressing a soft‐tissue membrane adjacent to the proximal tibia. A titanium plate was fixed to the bone surface. After 28 days of osseointegration of the plate, a 1‐mm‐wide gap was created between it and the cortical bone and 5 days were given for fibrous tissue to form. Load was transmitted to this soft tissue by applying force on a piston mounted in the plate. In six rats, a cyclic pressure of 0.6 MPa was then applied to this tissue by 20 cycles twice a day with a frequency of 0.17 Hz for 5 days. The remaining rats served as controls, with the piston left untouched in its upper position. All of the rats were killed 10 days after creation of the gap. Histological sections were produced at a right angle to the loaded surface, In the pressurized specimens, osteoclastic bone resorption was dramatic. In all specimens, the original cortex was almost entirely resorbed but new woven bone had formed deeper in the marrow and walled off a cystic lesion. When necrotic remnants of the cortex were still in place, new woven bone was seen on the side away from the piston. This “lee effect” may indicate that bone formation was inhibited by fluid flow away from the pressurized tissue. The specimens with a nonloaded piston showed no signs of resorption. This new experimental model shows again that a moderate rise of hydrostatic pressure at the interface of bone and implant leads to considerable bone resorption. This could be a mechanism of prosthetic loosening.
Effects of hydroxyapatite coating on Ti‐6 Al‐4V implant‐site infection in a rabbit tibial model
Authors: Vogely H. Ch. , Oosterbos C. J. M. , Puts E. W. A. , Nijhof M. W. , Nikkels P. G. J. , Fleer A. , Tonino A. J. , Dhert W. J. A. , Verbout A. J. 
Published: February 2005

AbstractTo investigate the effect of implant type after direct contamination, a hydroxyapatite‐coated or noncoated Ti‐6Al‐4V implant was inserted into both tibiae of 32 New Zealand White rabbits. Prior to implantation, the left tibia was contaminated with increasing concentrations of Staphylococcus aureus (102‐105 colony‐forming units), ranging from very low (102) to relatively high (105). Four weeks after implantation, half of the tibial bone adjacent to the implant was harvested for bacteriological examination. Bacterial counts were quantified by plating serial dilutions. For the histological evaluation, sections of the implant with the remaining tibia were examined by semiquantitative scoring of infection parameters. The bacteriological data showed the inoculum dose and implant type to have a significant effect on the culture outcome: more bacteria were retrieved from the hydroxyapatite‐coated implants than from the noncoated titanium implants. Histological evaluation showed an increased score for the infected left tibiae compared with their contralateral control. In addition, with increasing inoculum dosage, the difference between the two types of implant increased. We demonstrated that infections can occur with biocompatible, noncemented implants and that they are related to the dose of the original inoculum. Bacteria were more likely to grow onto or next to the hydroxyapatite implants than on titanium implants and resulted in a more severe histopathological characterization of infection.
Biological and mechanical characteristics of the interface between a new swelling anchor and bone
Authors: Gualtieri Gina M. , Siegler Sorin , Hume Eric L. , Kalidindi Surya R. 
Published: February 2005

AbstractWe recently evaluated the peak pullout loads for anchors made from our new copolymeric swellingtype material compared with anchors made of a nonswelling material. In vitro and in vivo peak pullout loads of these anchors were evaluated after different intervals of implantation in the lateral femoral condyles of New Zealand White rabbits. Scanning electron microscopy and energy dispersive x‐ray analyses were additionally performed on selected retrieved samples after pullout to examine the characteristics of bone attachment to the implant. The mean peak pullout load was greater for the swelling anchors than for the nonswelling anchors after 48 hours in vitro (46.0 ± 15.8 compared with 10.8 ± 9.1 N, p = 0.0541). After 2 weeks in vivo, it was significantly greater for the swelling anchors than for the nonswelling controls (177.7 ± 41.3 compared with 53.7 ± 17.5 N, p = 0.0024). The peak pullout load was also greater for the swelling anchors after 8 weeks in vivo; however, this difference was less pronounced than at 2 weeks (101.8 ± 35.0 compared with 58.9 ± 9.7 N, p = 0.0508). Furthermore, the swelling implants tended to induce bone deposition at the bone‐implant interface. Results from this investigation reveal that the new family of dynamic implants has potential for applications requiring fixation to cancellous or osteoporotic bone.
Anatomical effects of periosteal elevation
Authors: Brownlow H. C. , Reed A. , Joyner C. , Simpson A. H. R. W. 
Published: February 2005

AbstractResearch that involves harvesting the periosteum is common. The exact technique of harvesting is rarely described: however, it may be of vital importance because techniques may vary in their ability to raise the osteogenic cambial layer, which is reported to be tightly adherent to the underlying cortex. This study was performed to define how the cambial and fibrous layers of the periosteum are affected by different techniques of stripping. The periosteum was raised from the tibia and the humerus of adult rabbits with four stripping techniques. The stripped bone surface was examined histologically and with a scanning electron microscope to determine whether the fibrous and cambial layers of the periosteum had been removed and whether there had been damage to the underlying cortex. The results from the two anatomical sites were the same. Raising the periosteum with cortical bone chips (shingling) or with a periosteal elevator removed both layers of the periosteum and caused considerable damage to the surface of the cortex. Raising the periosteum with a sharp scalpel or by simply pulling it off removed the fibrous layer but left the osteogenic layer intact adherent to the cortex. We conclude that some techniques of periosteal elevation fail to harvest the osteogenic layer and therefore may lead to unexpected experimental results. We suggest that authors describe the exact technique of periosteal stripping that was employed.
Rapid quantitative bioassay of osteoinduction
Authors: Adkisson Huston Davis , Strauss‐Schoenberger Jena , Gillis Mary , Wilkins Ross , Jackson Marc , Hruska Keith A. 
Published: February 2005

AbstractWe developed a reproducible, relatively rapid bioassay that quantitatively correlates with the osteoinductive capacity of demineralized bone matrix obtained from human long bones. We have found that Saos human osteosarcoma cells proliferate in response to incubation with demineralized bone matrix and that an index of this proliferative activity correlates with demineralized bone matrix‐induced osteogenesisin vivo. The bioassay (Saos cell proliferation) had an interassay coefficient of variation of 23 ± 2% and an intra‐assay cocfficient of 11 ± 1%. Cell proliferation was normalized to a standard sample of demineralized bone matrix with a clinically high osteoinductive capacity, which was assigned a value of one. The Saos cell proliferation for each sample was related to the standard and assigned a value placing it into thc low (0.00‐0.39), intermediate (0.40‐0.69). or high (0.70‐1.49) osteoinductivc index group. Osteoinduction of human demineralized bone matrix was quantitated by expressing new bone formation as a function of the total bone volume (new bone plus the demineralized bone powder). The demineralized bone matrix was placed in pouches formed in the rectus abdominis muscles of athymic rats, and endochondral bone formation was assessed at 35 days following implantation, when marrow spaces in the ossicles were formed by new bone bridging the spaces between demineralized bone matrix particles. The proliferative index correlated with the area of new bone formation in histological sections ol the newly formed ossicles. When the proliferative index (the osteoinductive index) was divided into low, intermediate. and high groups, the correlation between it and new bone formation (osteoinduction) was 0.850 (p < 0.0005) in 25 samples of demineralized bone matrix. There was no overlap in the osteoinduction stimulated between the samples with low and high osteoinductive indices. We conclude that the proliferation assay is useful for the routine screening of bone allograft donors for osteoinductivc potential. Furthermore, the two‐dimensional area of new bone formation. as it relates to total new bone area, is a quantitative measure of osteoinduction.
Decorin antisense gene therapy improves functional healing of early rabbit ligament scar with enhanced collagen fibrillogenesis in vivo
Authors: Nakamura Norimasa , Hart David A. , Boorman Richard S. , Kaneda Yasufumi , Shrive Nigel G. , Marchuk Linda L. , Shino Konsei , Ochi Takahiro , Frank Cyril B. 
Published: February 2005

AbstractInjured ligaments heal with scar tissue, which has mechanical properties inferior to those of normal ligament, potentially resulting in re‐injury, joint instability, and subsequent degenerative arthritis. In ligament scars, normal large‐diameter collagen fibrils have been shown to be replaced by a homogenous population of small collagen fibrils. Because collagen is a major tensile load‐bearing matrix element and because the proteoglycan decorin is known to inhibit collagen fibrillogenesis, we hypothesized that the restoration of larger collagen fibrils in a rabbit ligament scar, by down‐regulating the proteoglycan decorin, would improve the mechanical properties of scar. In contrast to sense and injection‐treated controls, in vivo treatment of injured ligament by antisense decorin oligodeoxynucleotides led to an increased development of larger collagen fibrils in early scar and a significant improvement in both scar failure strength (83–85% improvement at 6 weeks; p < 0.01) and scar creep elongation (33–48% less irrecoverable creep; p < 0.03) under loading. This is the first report that in vivo manipulation of collagen fibrillogenesis improves tissue function during repair processes with gene therapy. These findings not only suggest the potential use of this type of approach to improve the healing of various soft tissues (skin, ligament, tendon, and so on) but also support the use of such methods to better understand specific structure‐function relationships in scars.
Tenascin‐C in tendon regions subjected to compression
Authors: Mehr D. , Pardubsky P. D. , Martin J. A. , Buckwalter J. A. 
Published: February 2005

AbstractTendon regions subjected almost exclusively to tension differ from regions subjected to high levels of compression as well as tension. Regions not exposed to compression consist primarily of spindle‐shaped fibroblasts surrounded by densely packed longitudinally oriented collagen fibrils formed principally from type‐I collagen. In contrast, regions subjected to compression have a fibrocartilagenous structure and composition: they consist of spherical cells surrounded by a matrix containing hyaline cartilage proteoglycans (aggrecan) and type‐II collagen as well as type‐I collagen. Reducing their adhesion to the matrix may help cells in the latter regions establish and maintain a spherical shape and minimize their deformation when the tissue is subjected to mechanical stress. We hypothesized that expression of tenascin‐C, an anti‐adhesive protein, is part of the adaptation of tendon cells to compression that helps establish and maintain fibrocartilagenous regions. To test this hypothesis, we compared segments of bovine flexor tendons subjected to repetitive compression (distal) with segments that are not subjected to compression (proximal) to determine whether they differed in tenascin‐C content and expression. RNA and protein analyses showed that tenascin‐C expression was elevated in the distal tendon. Tendon cells from the distal segment expressed more tenascin‐C mRNA than did cells from the proximal segments for as long as 4 days in cell culture, indicating that increased tenascin‐C expression is a relatively stable feature of the distal cells. Moreover, purified tenascin‐C inhibited the attachment of cultured tendon cells to fibronectin. These observations support the hypothesis that tenascin‐C expression is a cellular adaptation to compression that helps establish and maintain fibrocartilagenous regions of tendons by decreasing cell‐matrix adhesion.
Increased matrix synthesis following adenoviral transfer of a transforming growth factor β1 gene into articular chondrocytes
Authors: Shuler Franklin D. , Georgescu Helga I. , Niyibizi Christopher , Studer Rebecca K. , Mi Zhibao , Johnstone Brian , Robbins Paul D. , Evans Christopher H. 
Published: February 2005

AbstractMonolayer cultures of lapine articular chondrocytes were transduced with first‐generation adenoviral vectors carrying lacZ or transforming growth factor β1 genes under the transcriptional control of the human cytomegalovirus early promoter. High concentrations of transforming growth factor β1 were produced by chondrocytes following transfer of the transforming growth factor β1 gene but not the lacZ gene. Transduced chondrocytes responded to the elevated endogenous production of transforming growth factor β1 by increasing their synthesis of proteoglycan, collagen, and noncollagenous proteins in a dose‐dependent fashion. The increases in collagen synthesis were not accompanied by alterations in the collagen phenotype; type‐II collagen remained the predominant collagen. Transforming growth factor β1 could not, however, rescue the collagen phenotype of cells that had undergone phenotypic modulation as a result of serial passaging. These data demonstrate that chondrocytes can be genetically manipulated to produce and respond to the potentially therapeutic cytokine transforming growth factor β1. This technology has a number of experimental and therapeutic applications, including those related to the study and treatment of arthritis and cartilage repair.
Molecular cloning, sequencing, and tissue and developmental expression of mouse cartilage oligomeric matrix protein (COMP)
Authors: Fang Carrie , Carlson Cathy S. , Leslie Michael P. , Tulli Hermina , Stolerman Elliot , Perris Roberto , Ni Ligong , Di Cesare Paul E. 
Published: February 2005

AbstractMouse cartilage oligomeric matrix protein cDNA was cloned and sequenced by a reverse transcription‐polymerase chain reaction. The open reading frame encoded a product of 755 amino acids that shares a high degree of identity to and possesses all the characteristic molecular features of both rat and human cartilage oligomeric matrix protein. This suggests that cartilage oligomeric matrix protein is highly conserved during evolution. The clone was 83, 84, and 95% indentical to human, bovine, and rat cartilage oligomeric matrix protein cDNA, respectively. In tissues from the adult mouse, cartilage oligomeric matrix protein was expressed not only in cartilage and tendon but in trachea, bone, skeletal muscle, eye, heart, and placenta as well, and no expression was found in other tissues. Immunohistology revealed that cartilage oligomeric matrix was deposited as early as 10 days post coitus in predifferentiated mouse embryo mesenchyme. It was detected in all cartilaginous tissues and in the skeletal muscles of the embryo at day 13. As development progressed, accumulation of cartilage oligomeric matrix protein was marked in the growth plate. At 19 days post coitus, it was prominently deposited in the hypertrophic zone of the growth plate, perichondrium, and periosteum and in the superficial layer of the articular cartilage surface but was absent in the more central areas of the epiphyseal cartilage. The restricted tissue distribution and expression of cartilage oligomeric matrix protein in developing as well as adult mouse tissues suggest the regulation of this protein at the transcriptional level. The findings reported herein are the first detailed characterization of the distribution of cartilage oligomeric matrix protein during early skeletal development of the mouse.
Influence of muscular activity on local mineralization patterns in metatarsals of the embryonic mouse
Authors: Tanck E. , Blankevoort L. , Haaijman A. , Burger E. H. , Huiskes R. 
Published: February 2005

AbstractThis study addressed the theory that local mechanical loading may influence the development of embryonic long bones. Embryonic mouse metatarsal rudiments were cultured as whole organs, and the geometry of the primary ossification center was compared with that of rudiments that had developed in utero. The mineralization front in vivo was found to be nearly straight, whereas in vitro it acquired a more convex shape due to a slower mineralization rate at the periphery of the mineralized cylinder. A poroelastic finite element analysis was performed to calculate the local distributions of distortional strain and fluid pressure at the mineralization front in the metatarsal during loading in vivo as a result of muscle contractions in the embryonic hindlimbs. The distribution of fluid pressure from the finite element analysis could not explain the difference in mineralization shape. The most likely candidate for the difference was the distortional strain, resulting from muscle contraction, which is absent in vitro, because its value at the periphery was significantly higher than in the center of the tissue. Without external loads, the mineralization process may be considered as pre‐programmed, starting at the center of the tissue and resulting in a spherical mineralization front. Strain modulates the rate of the mineralization process in vivo, resulting in the straight mineralization front. These results confirm that disturbances in muscle development are likely to produce disturbed mineralization patterns, resulting in a disordered osteogenic process.