bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue distribution and measurement of cartilage oligomeric matrix protein in patients with magnetic resonance imaging‐detected bone bruises after acute anterior cruciate ligament tears
Authors: Fang Carrie , Johnson Darren , Leslie Michael P. , Carlson Cathy S. , Robbins Matthew , Cesare Paul E. Di 
Published: July 2002

AbstractHistologic and immunostaining analyses were performed on articular cartilage/subchondral bone biopsy specimens overlying MRI‐detected bone bruises in 12 patients with anterior cruciate ligament (ACL) tears. Staining with toluidine blue for proteoglycan revealed loss of staining from the superficial portion of the articular cartilage. Immunostaining for cartilage oligomeric matrix protein (COMP) showed an increased staining in the superficial matrix of the articular cartilage. Using polyclonal antisera against COMP, the authors performed a competitive enzyme‐linked immunosorbent assay (ELISA) on the synovial fluid from the injured and uninjured knees. There was an approximately 10‐fold higher synovial fluid COMP levels in injured knees. The COMP levels were greater in those patients who had synovial fluid samples harvested closer to the date of initial injury. Western blot analysis of the synovial fluid showed an increased presence of COMP degradation fragments from injured knees. These results are indicative of a significant injury to the articular cartilage, and may represent preclinical posttraumatic osteoarthritic lesions. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The enhancement of periosteal chondrogenesis in organ culture by dynamic fluid pressure
Authors: Mukherjee Niley , Saris Daniel B. F. , Schultz Fredrick M. , Berglund Lawrence J. , An Kai N. , O'Driscoll Shawn W. 
Published: July 2002

AbstractCartilage repair by autologous periosteal arthroplasty is enhanced by continuous passive motion (CPM) of the joint after transplantation of the periosteal graft. However, the mechanisms by which CPM stimulate chondrogenesis are unknown. Based on the observation that an oscillating intra‐synovial pressure fluctuation has been reported to occur during CPM (0.6–10 kPa), it was hypothesized that the oscillating pressure experienced by the periosteal graft as a result of CPM has a beneficial effect on the chondrogenic response of the graft. We have developed an in vitro model with which dynamic fluid pressures (DFP) that mimic those during CPM can be applied to periosteal explants while they are cultured in agarose gel suspension. In this study periosteal explants were treated with or without DFP during suspension culture in agarose, which is conducive to chondrogenesis. Different DFP application times (30 min, 4 h, 24 h/day) and pressure magnitudes (13, 103 kPa or stepwise 13 to 54 to 103 kPa) were compared for their effects on periosteal chondrogenesis. Low levels of DFP (13 kPa at 0.3 Hz) significantly enhanced chondrogenesis over controls (34 ± 7% vs 14 ± 5%; P < 0.05), while higher pressures (103 kPa at 0.3 Hz) completely inhibited chondrogenesis, as determined from the percentage of tissue that was determined to be cartilage by histomorphometry. Application of low levels of DFP to periosteal explants also resulted in significantly increased concentrations of Collagen Type II protein (43 ± 8% vs 10 ± 5%; P < 0.05). New proteoglycan synthesis, as measured by 35S‐sulphate uptake was increased by 30% in periosteal explants stimulated with DFP (350 ± 50 DPM vs 250 ± 75 DPM of 35S‐sulphate uptake/μg total protein), when compared to controls though this difference was not statistically significant. The DFP effect at low levels was dose‐dependant for time of application as well, with 4 h/day stimulation causing significantly higher chondrogenesis than just 30 min/day (34 ± 7 vs 12 ± 4% cartilage; P < 0.05) and not significantly less than that obtained with 24 h/day of DFP (48 ± 9% cartilage, P < 0.05). These observations may partially explain the beneficial effect on cartilage repair by CPM. They also validate an in vitro model permitting studies aimed at elucidating the mechanisms of action of mechanical factors regulating chondrogenesis. The fact that these tissues were successfully cultured in a mechanical environment for six weeks makes it possible to study the actions of mechanical factors on the entire chondrogenic pathway, from induction to maturation. Finally, these data support the theoretical predictions regarding the role of hydrostatic compression in fracture healing. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Signal transduction pathways and apoptosis in bacteria infected chondrocytes
Authors: Lee Mel S. , Yen Chen‐Yu , Ueng Steve W. N. , Shih Chun‐Hsiung , Chao Chuck C. K. 
Published: July 2002

AbstractThe mechanism underlying chronic destructive arthropathy after pyogenic arthritis is not clear. This study evaluated the role of apoptosis in Staphylococcus aureus infected human articular chondrocytes and investigated the signal transduction pathways activated by bacterial infection. Chondrocytes cultured in monolayer were challenged with bacteria for 6 h and were analyzed after incubation for 2, 18, and 24 h. Chondrocytes showed morphologic and biochemical evidences of apoptosis after infection and the following incubation period. Although treatment with extensive washing and vancomycin could ameliorate the amount of apoptosis from 31% to 15% at 2 h, from 48% to 23% at 18 h, and from 58% to 33% at 24 h, the infected samples with treatment still had higher amount of apoptosis than the un‐infected controls (ANOVA P < 0.001). Accompanying with the increasing amount of apoptosis, the caspase activity was upregulated in bacteria infected samples and remained high in samples with treatment (ANOVA P < 0.05). Signal transduction pathways activated by bacterial infection were assessed by co‐transfection technique. After infection, the c‐Jun N‐terminal kinase, extracellular signal‐regulated kinase, and cyclic AMP‐dependent protein kinase activities were elevated by 7.6‐, 7.3‐, and 3.2‐fold, respectively, compared to the uninfected controls. The data support the hypothesis that human chondrocytes will undergo apoptosis after infection by a single organism. Apoptosis and activated intracellular kinase activities may be related to the pathogenesis of post‐infectious destructive arthropathy. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Insulin‐like growth factor‐I gene expression patterns during spontaneous repair of acute articular cartilage injury
Authors: Fortier Lisa A. , Balkman Cheryl E. , Sandell Linda J. , Ratcliffe Anthony , Nixon Alan J. 
Published: July 2002

AbstractThis study evaluated the constitutive insulin‐like growth factor‐I (IGF‐I) gene expression pattern in spontaneously healing cartilage defects over the course of 16 weeks, and correlated the tissue morphology and matrix gene expression with IGF‐I mRNA levels. Full‐thickness 15 mm cartilage defects were debrided in the femoral trochlea of both femoropatellar joints of 8 horses and the healing defects examined 2, 4, 8, or 16 weeks after surgery. Samples were harvested for histologic assessment of tissue healing using H&E staining, toluidine blue histochemical reaction for proteogiycan deposition, and in situ hybridization and immunohistochemistry procedures to demonstrate collagen type II mRNA and protein expression. Total RNA was isolated for Northern analysis to measure cartilage matrix molecule expression, and for semi‐quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) to determine IGF‐I gene expression patterns in healing cartilage defects. Full‐thickness cartilage defects in horses were slow to heal compared to smaller lesions in similar locations in other animals. However, a progressive decline in tissue cellularity and vascularity, and increased tissue organization were observed on H&E stained specimens over the 16‐week experiment. Evidence of early chondrogenic repair was detected through collagen type II in situ hybridization and immunohistochemistry. However, levels of collagen type II and aggrecan mRNA in lesions were not abundant on Northern analysis indicating incomplete chondrogenesis. IGF‐I message expression followed a cyclic pattern with low levels at 2 weeks, followed by an increase at 4 and 8 weeks, and a subsequent decline at 16 weeks. There was no direct correlation between the stage of healing and cartilage matrix message expression, and the abundance of IGF‐I mRNA in the healing lesions. In conclusion, this study demonstrated that the spontaneous healing of articular defects was accompanied by a temporal fluctuation in IGF‐I gene expression which was discoordinate to the steady rise in expression of cartilage matrix molecules such as procollagen type II. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The effect of NKISK on tendon in an in vivo model
Authors: Caprise Peter A. , Lester Gayle E. , Weinhold Paul , Hill Jeff , Dahners Laurence E. 
Published: July 2002

AbstractThe mechanism through which ligaments and tendons change length during growth and contracture is unclear. It has been hypothesized that there is a reversible “interfibrillar bond” that, when broken, allows the sliding of collagen fibrils past one another during length changes. The pentapeptide NKISK has been reported to inhibit the binding of decorin to fibronectin. This study was designed to evaluate the effect of NKISK in an in vivo model. Male Sprague—Dawley rats were divided into three groups (n=9, 9 and 14, respectively). The left patellar tendon was injected with 1.0 ml of NKISK (Group 1 = 1.0 mM, Groups 2 and 3 = 5.0 mM). The contralateral/control limb was injected with carrier. Group 1 was sacrificed after three. Group 2 after four and Group 3 after seven daily injections. The patellar tendon lengths were measured in all groups with comparisons made to the contralateral control limb. NKISK injection resulted in a significant increase in length in Group 2 (3.14% ± 2.04, P = 0.002) and in Group 3 (6.12% ± 3.84, P < 0.001). Biomechanical testing of Group 3 showed no differences in maximum load, ultimate strength, structural stiffness, or elastic modulus of the treated tendons but did demonstrate a statistically significant decrease in the displacement and strain at maximum load in the NKISK‐treated tendons. This study demonstrates that inhibition of decorin/fibronectin binding by NKISK results in tendon lengthening in an in vivo setting as noted by a progressive increase in the length of the patellar tendon. © 2001 Orthopaedic Research Society. Punlished by Elsevier Science Ltd. All rights reserved.
Autologous chondrocyte implantation in a canine model: change in composition of reparative tissue with time
Authors: Breinan H. A. , Minas T. , Hsu H‐P. , Nehrer S. , Shortkroff S. , Spector M. 
Published: July 2002

AbstractThe objective of the study was to evaluate the tissue types filling 4‐mm diameter defects in the canine trochlear groove 1.5, 3, and 6 months after autologous chondrocyte implantation (ACI). Untreated defects served as controls. Periosteum alone controls were also included at the 1.5‐month time period. The results were compared with previously published findings obtained 12 and 18 months postoperative. After 3 months the ACI‐treated defects contained significantly more reparative tissue than found in the untreated control group, including twice the amount of hyaline cartilage (HC). These findings, however, were the only significant effects of the ACI treatment when compared to the periosteum alone or empty control groups. The benefits of ACI found at 3 months did not persist to longer time periods. An evaluation of the inter‐observer error associated with the histomorphometric method indicated that it was generally less than the inter‐animal variation in the results. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Origin and pathway of sensory nerve fibers to the ventral and dorsal sides of the sacroiliac joint in rats
Authors: Murata Yasuaki , Takahashi Kazuhisa , Masatsune  , Yamagata  , Takahashi Yuzuru , Shimada Yutaka , Moriya Hideshige 
Published: July 2002

AbstractThe purpose of this study is to clarify sensory innervation in the ventral and dorsal sides of the sacroiliac joint. Fluoro‐gold, a neural tracer, was injected into the left sacroiliac joint of adult rats from the dorsal side after denervation of the dorsal side, and the bilateral dorsal root ganglia (DRGs) from T13 to S4 were examined by fluorescence microscopy five days after injection. In another rat group, the DRGs were examined using the same methods after injection of fluoro‐gold from the ventral side. In the case of dorsal denervation (ventral nerve supply), labeled neurons were mainly located in the ipsilateral DRGs from L1 to S2. On the other hand, in the case of ventral denervation (dorsal nerve supply), labeled neurons were noted in the ipsilateral DRGs from L4 to S2. The sacroiliac joint in rats is innervated differently on the ventral and dorsal sides: the sensory nerve fibers to the dorsal side of the sacroiliac joint were derived from the DRGs of lower lumbar and sacral levels (from L4 to S2); and those to the ventral side from the DRGs of upper lumbar, lower lumbar, and sacral levels (from L1 to S2). © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Q‐angle influences tibiofemoral and patellofemoral kinematics
Authors: Mizuno Yasayuki , Kumagai Masaru , Mattessich Stephen M. , Elias John J. , Ramrattan Navin , Cosgarea Andrew J. , Chao Edmund Y. S. 
Published: July 2002

AbstractNumerous surgical procedures have been developed to correct patellar tracking and improve patellofemoral symptoms by altering the Q‐angle (the angle between the quadriceps load vector and the patellar tendon load vector). The influence of the Q‐angle on knee kinematics has yet to be specifically quantified, however. In vitro knee simulation was performed to relate the Q‐angle to tibiofemoral and patellofemoral kinematics. Six cadaver knees were tested by applying simulated hamstrings, quadriceps and hip loads to induce knee flexion. The knees were tested with a normal alignment, after increasing the Q‐angle and after decreasing the Q‐angle. Increasing the Q‐angle significantly shifted the patella laterally from 20° to 60° of knee flexion, tilted the patella medially from 20° to 80° of flexion, and rotated the patella medially from 20° to 50° of flexion. Decreasing the Q‐angle significantly tilted the patella laterally at 20° and from 50° to 80° of flexion, rotated the tibia externally from 30° to 60° of flexion, and increased the tibiofemoral varus orientation from 40° to 90° of flexion. The results show that an increase in the Q‐angle could lead to lateral patellar dislocation or increased lateral patellofemoral contact pressures. A Q‐angle decrease may not shift the patella medially, but could increase the medial tibiofemoral contact pressure by increasing the varus orientation. © 2001 Orthopaedic Research Society. Punlished by Elsevier Science Ltd. All rights reserved.
Cadherins: molecular codes for axon guidance and synapse formation
Authors: Ranscht Barbara 
Published: July 2002

AbstractThe formation of the myriad of neuronal connections within the vertebrate nervous system relies on expression of molecular tags that match extending axon populations with synaptic target sites. Recent work suggests that cadherins, a group of calcium‐dependent cell adhesion molecules, are candidates to serve such a role. The diversity of the cadherin family in the nervous system allows for a multitude of interactions to specify neuronal connections. Specific cadherin types demarcate subpopulations of developing axons that interconnect within neuronal circuits. Expression of different cadherin species at select synapse populations raises exciting prospects for this molecule class in controlling adhesive interactions during synaptogenesis and plasticity. Regulation of cadherin‐mediated adhesive strength is an attractive mechanism to explain the different cadherin functions in axon growth and at synapses.
Prolactin concurrently activates Src‐PLD and JAK/Stat signaling pathways to induce proliferation while promoting differentiation in embryonic astrocytes
Authors: Mangoura Dimitra , Pelletiere Chris , Leung Soyan , Sakellaridis Nikos , Wang De Xin 
Published: July 2002

AbstractIn normal development, embryonic astrocytes progress through their cell lineage by acquiring differentiation, by apoptosis, and by proliferation. In this study, we show that embryonic astrocytes may maintain and make gains in differentiation as they simultaneously progress through one cell cycle when induced by prolactin (PRL). Prolactin induced the majority of astrocytes to incorporate bromodeoxyuridine (BrdU) with a four‐fold increase over controls after 18 h of exposure. Investigating possible mitogenic signaling pathways we show for the first time that prolactin is coupled to a sustained phospholipase D (PLD) activation, with an efficacy similar to the phorbol ester and astrocytic mitogen 12‐tetradecanoylphorbol‐13‐acetate (TPA). Both cyclosporine and suramin abolished this activation. Staurosporine and calphostin C also inhibited the PRL effect by 50%, consistent with involvement of protein kinase C‐(PKC)‐α, the major PKC isoform in astrocytes. Genistein and PP1 blocked the activation indicating additional regulation by cytosolic tyrosine kinases. This profile of PLD activation was suggestive of a PLD I isoform and a mitogenic response. Upon completion of the cell cycle, analysis of glia fibrillary acidic protein (GFAP) and vimentin abundance, and glutamine synthetase (GS) activity showed that astrocytes had gained in expression of differentiation markers. Moreover, the intensity of GFAP immunofluorescence was greater per cell, as was the length of the cell processes. In exploring the signaling for prolactin‐induced differentiation we found that prolactin activated the tyrosine kinase Janus kinase (JAK) 2 and significantly stimulated tyrosine, phosphorylation of the prolactin receptor. Stat 1 and 3 were also activated presumably downstream to JAK2 activation. A rapid translocation of the cytosolic Stats over the nucleus was seen in nearly every astrocyte corresponding well with the gains in GFAP per cell. The Stats translocation did not depend on MEK‐ERK inhibition by PD98059, inhibition of p38 by 1 μm SB203580, or Src kinase family inhibition by PP1. Our results demonstrate the ability of PRL to concurrently induce activation of PLD, a mitogenic signaling pathway in astrocytes, and prolonged stimulation of Stat1, compatible with the increased GFAP upregulation and cell differentiation. Considered together this data may provide an explanation on the fast gain in both numbers and differentiation in the astrocytic population during development (HD 09402, CRF).
Involvement of astrocytes in purine‐mediated reparative processes in the brain
Authors: Ciccarelli R. , Ballerini P. , Sabatino G. , Rathbone M.P. , D'Onofrio M. , Caciagli F. , Di Iorio P. 
Published: July 2002

AbstractAstrocytes are involved in multiple brain functions in physiological conditions, participating in neuronal development, synaptic activity and homeostatic control of the extracellular environment. They also actively participate in the processes triggered by brain injuries, aimed at limiting and repairing brain damages. Purines may play a significant role in the pathophysiology of numerous acute and chronic disorders of the central nervous system (CNS). Astrocytes are the main source of cerebral purines. They release either adenine‐based purines, e.g. adenosine and adenosine triphosphate, or guanine‐based purines, e.g. guanosine and guanosine triphosphate, in physiological conditions and release even more of these purines in pathological conditions. Astrocytes express several receptor subtypes of P1 and P2 types for adenine‐based purines. Receptors for guanine‐based purines are being characterised. Specific ecto‐enzymes such as nucleotidases, adenosine deaminase and, likely, purine nucleoside phosphorylase, metabolise both adenine‐ and guanine‐based purines after release from astrocytes. This regulates the effects of nucleotides and nucleosides by reducing their interaction with specific membrane binding sites. Adenine‐based nucleotides stimulate astrocyte proliferation by a P2‐mediated increase in intracellular [Ca2+] and isoprenylated proteins. Adenosine also, via A2 receptors, may stimulate astrocyte proliferation, but mostly, via A1 and/or A3 receptors, inhibits astrocyte proliferation, thus controlling the excessive reactive astrogliosis triggered by P2 receptors. The activation of A1 receptors also stimulates astrocytes to produce trophic factors, such as nerve growth factor, S100β protein and transforming growth factor β, which contribute to protect neurons against injuries. Guanosine stimulates the output of adenine‐based purines from astrocytes and in addition it directly triggers these cells to proliferate and to produce large amount of neuroprotective factors. These data indicate that adenine‐ and guanine‐based purines released in large amounts from injured or dying cells of CNS may act as signals to initiate brain repair mechanisms widely involving astrocytes.
Muscle activity‐resistant acetylcholine receptor accumulation is induced in places of former motor endplates in ectopically innervated regenerating rat muscles
Authors: Gašperšič Rok , Koritnik Blaž , Eržen Ida , Sketelj Janez 
Published: July 2002

AbstractExpression of acetylcholine receptors (AChRs) in the extrajunctional muscle regions, but not in the neuromuscular junctions, is repressed by propagated electric activity in muscle fibers. During regeneration, subsynaptic‐like specializations accumulating AChRs are induced in new myotubes by agrin attached to the synaptic basal lamina at the places of former motor endplates even in the absence of innervation. We examined whether AChRs still accumulated at these places when the regenerating muscles were ectopically innervated and the former synaptic places became extrajunctional. Rat soleus muscles were injured by bupivacaine and ischemia to produce complete myofiber degeneration. The soleus muscle nerve was permanently severed and the muscle was ectopically innervated by the peroneal nerve a few millimeters away from the former junctional region. After 4 weeks of regeneration, the muscles contracted upon nerve stimulation, showed little atrophy and the cross‐section areas of their fibers were completely above the range in non‐innervated regenerating muscles, indicating successful innervation. Subsynaptic‐like specializations in the former junctional region still accumulated AChRs (and acetylcholinesterase) although no motor nerve endings were observed in their vicinity and the cross‐section area of their fibers clearly demonstrated that they were ectopically innervated. We conclude that the expression of AChRs at the places of the former neuromuscular junctions in the ectopically innervated regenerated soleus muscles is activity‐independent.