bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early medial collateral ligament scars have inferior creep behaviour
Authors: Thornton G. M. , Leask G. P. , Shrive N. G. , Frank C. B. 
Published: February 2005

AbstractRecent evidence suggests that ligaments are subject to repetitive loads in vivo. Hence, the creep behaviour (increase in strain under constant or repetitive stress) of ligament scars is of significance, since healing ligaments may elongate permanently over time. A rabbit medial collateral ligament model was used to assess the creep behaviour of healing ligaments at stresses corresponding to 30% of the scar failure strength at 3 (n = 6), 6 (n = 6), and 14 (n = 5) weeks of healing. The stresses for the creep tests of scars (and contralateral controls) were 2.2, 4.1, and 7.1 MPa for the 3.6, and 14‐week healing intervals, respectively. Normal medial collateral ligaments from comparable rabbits were tested at two of the corresponding stresses: 4.1 (n = 7) and 7.1 (n = 6) MPa. Total creep strain—the cumulative increase in strain resulting from serial cyclic and static creep testing—was independent of the order of testing and was compared between scars and controls. Water contents after testing were also quantified. Water contents before testing were assessed for additional animals: six normal animals and three from each healing interval. At 3 weeks of healing, the total creep strain of medial collateral ligament scars was four times greater than that for contralateral controls tested at the same stress. Although there was improvement from 3 to 14 weeks, the total creep strain of scars remained more than two times greater than that of controls at 14 weeks. Scar water content decreased with healing from elevated initial values, possibly contributing to the marginally improved creep response. Comparisons of this deficiency in scar creep with previously published scar abnormalities in the same model suggest that collagen crosslink density, proteoglycan content, soft‐tissue flaws, and the combined effect of collagen fibre changes may be mechanistic factors involved in scar creep.
Longitudinal characterization of synovial fluid biomarkers in the canine meniscectomy model of osteoarthritis
Authors: Lindhorst E. , Vail T. P. , Guilak F. , Wang H. , Setton L. A. , Vilim V. , Kraus V. B. 
Published: February 2005

AbstractDamage to the meniscus can lead to posttraumatic osteoarthritis. Early markers of joint injury and tissue disease may be useful in developing and administering clinical treatment. We investigated the effects of total medial meniscectomy on biomarkers measured serially in synovial lavage fluid each month for 3 months. Following meniscectomv in dogs, four biomarkers were evaluated: cartilage oligomeric matrix protein, keratan sulfate epitope (5D4), the 3B3(−) neoepitope of chondroitin‐6‐sulfate, and the 3B3(+) chondroitinasegenerated epitope of chondroitin‐6‐sulfate. Meniscectomy led to statistically significant elevations of all four biomarkers, with levels peaking at 4 weeks. By 12 weeks, the level of the 5D4 epitope returned to the preoperative baseline level whereas that of cartilage oligomeric matrix protein, 3B3(−), and 3B3(+) remained above the baseline. Concentrations of these biomarkers in the knees not operated on did not change significantly from the baseline. The levels of cartilage oligomeric matrix protein and 3B3(−) relative to 3B3(+) remained constant in all knees. In contrast, the level of 5D4 relative to 3B3(+) declined over time in the knee operated on but remained constant in the knee not operated on. These results demonstrate a quantitative change in the molecular components of synovial fluid after meniscectomy, as well as a qualitative change evinced by an alteration in the relative proportions of these epitopes. Extensive analyses showed a strong correlation between serum levels of 3B3(−) from the femoral and cephalic veins; however, serum 3B3(−) was not correlated with synovial fluid 3B3(−). These findings support the hypothesis that the concentrations of select cartilage biomarkers in synovial fluid are altered following meniscectomy and are promising tools for objectively monitoring the induction of osteoarthritis in this model system.
Mechanical compression modulates proliferation of transplanted chondrocytes
Authors: Li Kelvin W. , Falcovitz Yehudit H. , Nagrampa Jennifer P. , Chen Albert C. , Lottman Lisa M. , Shyy John Y‐J. , Sah Robert L. 
Published: February 2005

AbstractThe presence of an appropriate number of reparative cells in an articular cartilage defect is probably necessary for consistent and successful repair. Following the transplantation of chondrocytes into a defect, cell proliferation may modulate local defect cellularity. Transplanted cells can be compressed during cartilage repair as a result of joint‐loading or press‐fitting a graft into a cartilage defect. The objective of this study was to characterize the proliferative response of chondrocytes after attachment to cartilage and application of static compressive stress between cartilaginous surfaces in an ex vivo model. The chondrocytes were isolated from adult bovine cartilage, cultured in high‐density monolayer, resuspended, and then transplanted onto the surface of devitalized cartilage at a density of 250,000 cells/cm2. The total DNA content of transplanted cell layers increased steadily to a plateau by 5 days and represented a 4‐fold increase in cell number during incubation in medium including serum and ascorbate. Over the culture period, the level of DNA synthesis ([3H]thymidine incorporation), on a per cell basis, decreased steadily (88% between days 0 and 6). The application of 24 hours of static compressive stress (0.06‐0.4 MPa) to the adherent cells at 1 and 4 days after transplantation inhibited overall DNA synthesis by 70‐∼87% compared with unloaded controls. After release from load, cell proliferation generally remained at low levels. The marked proliferation of chondrocytes when attached to cartilage without applied load and the inhibition of this proliferation by relatively low‐amplitude static compressive stress may be relevant to the occasional overgrowth of tissue in some chondrocyte transplantation procedures. The dosimetry of these effects suggests that the in vivo mechanical environment may have a marked effect on proliferation of transplanted chondrocytes.
Mechanical modulation of tenascin‐C and collagen‐XII expression during avian synovial joint formation
Authors: Mikic Borjana , Wong Marcy , Chiquet Matthias , Hunziker Ernst B. 
Published: February 2005

AbstractThe objective of this study was to investigate how temporal and spatial patterns of characteristic extracellular matrix molecules are altered in the absence of normal functional skeletal muscle contractions during avian synovial joint development. By using in situ detection of protein and mRNA expression in developing avian feet and femorotibial joints from a wide range of developmental stages, we demonstrate that the morphological abnormalities that result from embryonic immobilization are associated with altered patterns of tenascin‐C and collagen‐XII expression within developing joint structures. As the joints fuse in immobilized embryos, the cells of the presumptive articular surface differentiate from flattened fibroblasts to more rounded chondrocytes and collagens XII and I are no longer detected at sites of complete joint fusion. Although the expression of collagen XII persists at normal levels elsewhere within the immobilized joint, tenascin‐C expression is diminished within the chondroepiphysis, synovium, and tendons, as well as within the remains of the fibrous articular surface. This effect is most notable for the shortest tenascin variant (Tn 190) within the chondroepiphysis and the largest variant (Tn230) within tendons, synovium, and the fibrous surface layer of the joint. This study thus provides in vivo support of previous in vitro work that suggests that tenascin expression is sensitive to external changes in mechanical loading environment. However, these data do not support a similar conclusion for collagen XII during early development.
Femoral structure and stiffness in patients with femoral neck fracture
Authors: Cody Dianna D. , Hou Fu J. , Divine George W. , Fyhrie David P. 
Published: February 2005

AbstractBone morphological characteristics may relate to the risk of hip fracture. We applied finite element modeling to radiologic data for two groups of women in vivo to address two questions: (a) Do individuals who have just sustained a femoral neck fracture exhibit reduced three‐dimensional structural stiffness? and (b) Are victims of hip fracture disproportionately more susceptible to loads sustained in a fall than to stance‐type loads? Ten white women (age: 64–76 years) who had just sustained a femoral neck fracture and 18 female volunteers (age: 65–76 years), matched as groups for race, age, and body mass index, were evaluated, From quantitative computed tomography scans, femoral morphometric and volumetric cancellous density measurements were obtained and a finite element model was constructed. Two load conditions were simulated: single‐stance phase and lateral fall. Global stiffness values were determined for each model. The cancellous bone density was significantly lower at the femoral neck and the femoral neck and head diameters were significantly larger in the women in the fracture group than in those in the control group. The stiffness of the proximal femur did not differ significantly between the groups for either load condition. An apparently linear relationship was found for stiffness at stance load compared with stiffness at fall load (r = 0.84, p < 0.001), and slopes did not differ significantly between the groups. Although cancellous density was reduced at the fracture site in patients with femoral neck fractures, this did not result in a reduction in the predicted bone stiffness. Previous studies have established a very strong relationship between the stiffness and strength of bone. Since these modeling methods were thoroughly validated ex vivo, we conclude that although decreased bone density at the femoral neck may predict where fracture initiates, the risk of hip fracture per se may be more strongly dependent on issues such as the risk of falling and fall biomechanics than on the structural characteristics of bone.
Knee pain and joint loading in subjects with osteoarthritis of the knee
Authors: Hurwitz D. E. , Ryals A. R. , Block J. A. , Sharma L. , Schnitzer T. J. , Andriacchi T. P. 
Published: February 2005

AbstractAlthough treatments for osteoarthritis of the knee are often directed at relieving pain, pain may cause patients to alter how they perform activities to decrease the loads on the joints. The knee‐adduction moment is a major determinant of the load distribution between the medial and lateral plateaus. Therefore, the interrelationship between pain and the external knee‐adduction moment during walking may be especially important for understanding mechanical factors related to the progression of medial tibiofemoral osteoarthritis. Fifty‐three subjects with symptomatic radiographic evidence of osteoarthritis of the knee were studied. These subjects were a subset of those enrolled in a double‐blind study in which gait analysis and radiographic and clinical evaluations were performed after a 2‐week washout of anti‐inflammatory and analgesic treatment. The subjects then took a nonsteroidal anti‐inflammatory drug, acetaminophen, or placebo for 2 weeks, and the gait and clinical evaluations were repeated. The change in the peak external adduction moment between the two evaluations was inversely correlated with the change in pain (R = 0.48, p < 0.001) and was significantly different between those whose pain increased (n = 7), decreased (n = 18), or remained unchanged (n = 28) (p = 0.009). Those with increased pain had a significant decrease in the peak external adduction (p = 0.005) and flexion moments (p = 0.023). In contrast, the subjects with decreased pain tended to have an increase in the peak external adduction moment (p = 0.095) and had a significant increase in the peak external extension moment (p = 0.017). The subjects whose pain was unchanged had no significant change in the peak external adduction (p = 0.757), flexion (p = 0.234), or extension (p = 0.465) moments. Thus, decreases in pain among patients with medial tibiofemoral osteoarthritis were related to increased loading of the degenerative portion of the joints. Additional long‐term prospective studies are needed to determine whether increased loading during walking actually results in accelerated progression of the disease.
Expression of cartilage oligomeric matrix protein (COMP) by embryonic and adult osteoblasts
Authors: Di Cesare Paul E. , Fang Carrie , Leslie Michael P. , Tulli Hermina , Perris Roberto , Carlson Cathy S. 
Published: February 2005

AbstractCartilage oligomeric matrix protein has been implicated as an important component of endochondral ossification because of its direct effects on chondrocytes. The importance of this protein for skeletal development and growth has been recently illustrated by the identification of mutations in cartilage oligomeric protein genes in two types of inherited chondrodysplasias and osteoarthritic phenotypes: multiple epiphyseal dysplasia and pseudoachondroplasia. In the present study, we report the presence of cartilage oligomeric protein in embryonic and adult osteoblasts. A foot from a 21‐week‐old human fetus, subchondral bone obtained from knee replacement surgery in an adult patient, and a limb from a 19‐day‐postcoital mouse embryo were analyzed with immunostaining and in situ hybridization. In the human fetal foot, cartilage oligomeric protein was localized to osteoblasts of the bone collar and at the newly formed bone at the growth plate and bone diaphyses. Immunostaining was performed on the adult subchondral bone and showed positive intra‐cellular staining for cartilage oligomeric protein of the osteoblasts lining the trabecular bone. There was no staining of the osteocytes. Immunostaining of the mouse limb showed the most intense staining for cartilage oligomeric protein in the hypertrophic chondrocytes and in the surrounding osteoblast cells of the developing bone. Cartilage oligomeric protein mRNA and protein were detected in an osteoblast cell line (MG‐63), and cartilage oligomeric protein mRNA was detected from human cancellous bone RNA. These results suggest that the altered structure of cartilage oligomeric protein by the mutations seen in pseudoachondroplasia and multiple epiphyseal dysplasia may have direct effects on osteoblasts, contributing to the pathogenesis of these genetic disorders.
Inhibitory effects of the quinolone antibiotics trovafloxacin, ciprofloxacin, and levofloxacin on osteoblastic cells in vitro
Authors: Holtom Paul D. , Pavkovic Steven A. , Bravos Peter D. , Patzakis Michael J. , Shepherd Lane E. , Frenkel Baruch 
Published: February 2005

AbstractWe studied the inhibitory effects of the fluoroquinolones levofloxacin, ciprofloxacin, and trova‐floxacin on growth and extracellular matrix mineralization in MC3T3‐E1 osteoblast‐like cell cultures. Levo‐floxacin had the least inhibitory effect on cell growth, with a 50% inhibitory concentration of approximately 80 μg/ml at 48 and 72 hours. Ciprofloxacin had an intermediate degree of inhibition, with a 50% inhibitory concentration of 40 μg/ml at 48 and 72 hours. Trovafloxacin exerted a profound inhibitory effect on cell growth, with a 50% inhibitory concentration of 0.5 μg/ml, lower than clinically achievable serum levels. The decreased cell counts with up to 2.5 μg/ml of trovafloxacin and with up to 40 μg/ml of ciprofloxacin were not associated with decreased rates of 5‐bromo‐2′‐deoxyuridine incorporation per cell. Alatrovafloxacin, the L‐alanyl‐l‐alanine prodrug of trovafloxacin, exerted effects on proliferation and 5‐bromo‐2′‐deoxyuridine incorporation similar to those of the parent compound. The quinolones evaluated also inhibited extracellular matrix mineralization by MC3T3‐E1 cells. Treatment of confluent cultures with trovafloxacin, ciprofloxacin, or levofloxacin resulted in strong inhibition of calcium deposition, as determined on day 14 by alizarin red staining and biochemical analysis. The effect was apparent with 2.5‐5 μg/ml of each of the three antibiotics tested and progressively increased to more than a 90% decline in the calcium/protein ratio with 20‐40 μg/ml antibiotic concentration. Further in vivo studies are advocated to evaluate the relevance of the in vitro cytotoxicity reported here to bone healing in orthopaedic patients.
Distribution of chondrocytes containing α‐smooth muscle actin in human articular cartilage
Authors: Kim A. C. , Spector M. 
Published: February 2005

AbstractRelatively little is known about the contractile behavior of the human articular chondrocyte. Other connective tissue cells are known to express a contractile actin isoform, α‐smooth muscle actin, in response to injury, at selected stages of wound healing, and in certain pathological conditions. This and recent work demonstrating contractile behavior in adult canine articular chondrocytes in vitro prompted the present study of the distribution of α‐smooth muscle actin‐containing chondrocytes in human articular cartilage. Approximately 75% of the chondrocytes in the superficial region of cartilage expressed α‐smooth muscle actin as demonstrated by immunohistochemistry. In contrast, only approximately 10% of the cells in the deep region stained for this contractile actin isoform. There was no correlation of the percentage of α‐smooth muscle actin‐positive cells in either region with Mankin grade or with age. This is the first report of a contractile potential for human articular chondrocytes. The roles of α‐smooth muscle actin in these cells warrant further investigation. The question of whether it is necessary to refer to these cells as myochondrocytes is considered.
Effects of harvest and selected cartilage repair procedures on the physical and biochemical properties of articular cartilage in the canine knee
Authors: Lee C. R. , Grodzinsky A. J. , Hsu H.‐P. , Martin S. D. , Spector M. 
Published: February 2005

AbstractThis study utilizes a canine model to quantify changes in articular cartilage 15–18 weeks after a knee joint is subjected to surgical treatment of isolated chondral defects. Clinical and experimental treatment of articular cartilage defects may include implantation of matrix materials or cells, or both. Three cartilage repair methods were evaluated: microfracture, microfracture and implantation of a type‐II collagen matrix, and implantation of an autologous chondrocyte‐seeded collagen matrix. The properties of articular cartilage in other knee joints subjected to harvest of articular cartilage from the trochlear ridge (to obtain cells for the cell‐seeded procedure) were also evaluated. Physical properties (thickness, equilibrium compressive modulus, dynamic compressive stiffness, and streaming potential) and biochemical composition (hydration, glycosaminoglycan content, and DNA content) of the cartilage from sites distant to the surgical treatment were compared with values measured for site‐matched controls in untreated knee joints. No significant differences were seen in joints subjected to any of the three cartilage repair procedures. However, a number of changes were induced by the harvest operation. The largest changes (displaying up to 3‐fold increases) were seen in dynamic stiffness and streaming potential of patellar groove cartilage from joints subjected to the harvest procedure. Whether the changes reported will lead to osteoarthritic degeneration is unknown, but this study provides evidence that the harvest procedure associated with autologous cell transplantation for treatment of chondral defects may result in changes in the articular cartilage in the joint.
Cellular contribution of bone graft to fusion
Authors: Gould Stephen E. , Rhee John M. , Tay Bobby K‐B. , Otsuka Norman Y. , Bradford David S. 
Published: February 2005

AbstractAlthough a number of studies have examined the fate of graft‐derived cells during the process of fusion, there remains no consensus regarding their exact contribution to bone formation within the fusion mass. We developed two chimeric mouse isograft fusion models that allowed us to track the fate of graft cells within the host fusion bed. Cortical/cancellous bone graft (1:1 ratio of pelvic to vertebral body bone) from male mice was placed between (a) the tibia and fibula or (b) the coccygeal spine transverse processes of syngeneic female hosts. Both models were characterized histologically and histochemically. Graft‐derived cells were then identified by fluorescent in situ hybridization for Y‐chromosome sequences present in only the graft (male) cells. When the fusion mass was healing but not yet fused (at 1 and 2 weeks), numerous graft‐derived cells were observed throughout the fusion site. The predominant graft‐derived cell types included chondrocytes, osteoblasts, and fibroblasts. Chondrocytes arose from precursor cells in the graft de novo, as cartilage was not transplanted during the surgical procedure. By the time a mature fusion mass had formed (at 6 weeks), graft‐derived cells persisted as osteocytes within the cortical rim surrounding the fusion mass. These osteocytes likely differentiated from graft‐derived precursors that had directly formed bone, because transplanted osteocytes within cortical bone graft fragments were noted to rarely survive even at 1 and 2 weeks. Collectively, our results demonstrate for the first time that bone graft contributes cells that, in conjunction with host cells, directly form bone within the fusion mass during all phases of fusion rather than just the early phases.
Murine model for skeletal metastases of Ewing's sarcoma
Authors: Scotlandi Katia , Benini Stefania , Manara Maria Cristina , Serra Massimo , Nanni Patrizia , Lollini Pier‐Luigi , Nicoletti Giordano , Landuzzi Lorena , Chano Tokuhiro , Picci Piero , Baldini Nicola 
Published: February 2005

AbstractEwing's sarcoma shows a strong tendency to metastasize to the lungs or the skeleton, or both. A peculiar feature of the secondary involvement of bone with this tumor is that it may also appear in the absence of clinically evident lung metastases, both at clinical presentation and during the course of the disease. Although osseous metastases are critically relevant for prognosis, the pathogenesis of this peculiar feature of Ewing's sarcoma is poorly understood, partly due to the lack of appropriate experimental in vivo models. We show that the intravenous injection of TC‐71 Ewing's sarcoma cells into athymic 4–5‐week‐old Crl/nu/nu (CD‐1) BR mice reproducibly colonizes specific sites of the skeleton in addition to the lungs and lymph nodes. The distribution and the morphologic appearance of these experimental bone metastases mimic the pattern of skeletal involvement observed in humans. This experimental model of bone metastasis of Ewing's sarcoma.