Journal of orthopaedic research : official publication of the Orthopaedic Research Society.
Publisher:
Raven Press,. Hoboken, NJ : Wiley (2006)
Frequency: Bimonthly, 1989-
Country: United States
Language: English
Author(s):
Bioelectric Repair and Growth Society., Orthopaedic Research Society.
Start Year:1983 -
ISSN:
0736-0266 (Print)
1554-527X (Electronic)
0736-0266 (Linking)
1554-527X (Electronic)
0736-0266 (Linking)
Impact Factor
2.8
2022
| NLM ID: | 8404726 |
| (DNLM): | J33365000(s) |
| (OCoLC): | 09069401 |
| Coden: | JOREDR |
| LCCN: | sn 82008603 |
| Classification: | W1 JO804SF |
Signaling through the small G-protein Cdc42 is involved in insulin-like growth factor-I resistance in aging articular chondrocytes. During aging, chondrocytes become unresponsive to insulin-like growth factor-I (IGF-I). This study examined the role of Cdc42 (cell-division-cycle 42) in IGF-I signaling during aging. Experiments were performed using cartilage and chondrocytes isolated from horses ages 1 day-25 years. Northern analysis was used to examine expression of the small GTPases Cdc42, Rac, and RhoA. Western analysis was utilized to assess total Cdc42 (GTP + GDP-bound); active, GTP-Cdc42 was assessed using a pulldown assay with Western analysis. GTP-Cdc42 was also measured following IGF-I treatment. Gene expression for...
Validation of an in vitro single-impact load model of the initiation of osteoarthritis-like changes in articular cartilage. The objective of this study was the development and characterization of an in vitro model of the initiation of traumatic osteoarthritis (OA). Articular cartilage was obtained from seven healthy horses and from four horses diagnosed with OA. Cartilage disks were subjected to a single-impact load (500 g from 25, 50, or 100 mm) using a simple drop-tower device and cultured in vitro for up to 20 days. Cartilage sections were examined histologically to observe surface damage and proteoglycan loss. Percentage cell death was determined using TUNEL, release of glycosaminoglycans (GAG) to the medium wa...
In vivo study on the short-term effect of radiofrequency energy on chondromalacic patellar cartilage and its correlation with calcified cartilage pathology in an equine model. Chondromalacia can cause joint pain and synovial effusion with the potential for developing into osteoarthritis. Thermal chondroplasty using radiofrequency energy (RFE) has been reported to be superior to mechanical debridement for treating chondromalacia. We compared short-term changes in biomechanical properties of articular cartilage after treatment with monopolar (mRFE) or bipolar RFE (bRFE) or mechanical debridement (MD) on experimentally created grade II chondromalacia patellae. Chondromalacia patellae was created arthroscopically in both patellae of 15 ponies. Ten months after surgery, ...
Expression of insulin-like growth factor binding proteins in healing tendon lesions. he treatment of overuse tendon injuries with exogenous growth factors such as insulin-like growth factor-I (IGF-I) may facilitate an improved return to sustained athletic function. The biological effects of IGF-I are exerted under the control of a complex of IGF receptors, binding proteins, and proteases. This IGF system includes a family of six structurally related high-affinity IGF binding proteins (IGFBPs) that protect IGF-I from local proteases and restrict access of IGF-I to its receptor. This study describes the expression of the IGFBPs in flexor tendon after acute injury and during heal...
Expression patterns of hedgehog signaling peptides in naturally acquired equine osteochondrosis. Hypertrophic differentiation and endochondral ossification of growth cartilage are regulated by a complex array of signaling peptides, including parathyroid hormone-related protein (PTH-rP), Indian hedgehog (Ihh), and bone morphogenetic proteins (BMPs). This study investigated the expression of Ihh, Patched1 and 2 (Ptc1, Ptc2), Smoothened (Smo), Gli1, and Gli3, in naturally acquired articular osteochondrosis, using an equine model. Cartilage was harvested from osteochondrosis (OC) affected femoropatellar or scapulohumeral joints from immature horses and normal control horses of similar age. Ih...
Repeated intraarticular injections of triamcinolone acetonide alter cartilage matrix metabolism measured by biomarkers in synovial fluid. Although intraarticular (IA) corticosteroids are frequently used to treat joint disease, the effects of their repeated use on articular cartilage remains controversial. The aim of our study was to determine the effects of a clinically recommended dose of IA triamcinolone acetonide (TA), on synovial fluid (SF) biomarkers of cartilage metabolism. Ten adult horses, free of osteoarthritis (OA) in their radiocarpal joints, were studied. One radiocarpal joint of each horse was randomly chosen for treatment and the contralateral anatomically paired joint acted as the control. Aseptic arthrocentesis w...
Enhanced concentration of COMP (cartilage oligomeric matrix protein) in osteochondral fractures from racing Thoroughbreds. The aim of the present study was to correlate the levels of COMP and aggrecan as indicators of tissue damage, in synovial fluid (sf) from carpal joints of acutely lame racehorses, with macroscopical lesions of articular cartilage (OA), osteochondral fractures and ligament tears found at arthroscopy. Sixty-three lame horses [49 Standardbred trotters (STB) and 14 Thoroughbreds (TB)] in conventional training and racing that underwent arthroscopy of their middle carpal or radiocarpal joints were included in the study. Intact as well as fragmented COMP and aggrecan released into the synovial fluid ...
Dual transduction of insulin-like growth factor-I and interleukin-1 receptor antagonist protein controls cartilage degradation in an osteoarthritic culture model. This study evaluated the potential of gene induced synoviocyte expression of a combination of insulin-like growth factor-I (AdIGF-I) and interleukin-1 receptor antagonist protein (AdIL-1Ra) to control articular cartilage degradation in vitro. Cartilage explants and synovial membrane were harvested from young mature horses. Synovial monolayers were established and either (1) maintained as untransduced controls; (2) transduced with AdIGF-I at 200 MOI in 500 microl serum-free medium; (3) transduced with AdIL-1Ra at 100 MOI; or (4) transduced with a combination of AdIGF-I (200 MOI) and AdIL-1Ra (1...
Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7. Cartilage has a limited capacity to heal. Although chondrocyte transplantation is a useful therapeutic strategy, the repair process can be lengthy. Previously we have shown that over expression of bone morphogenetic protein-7 (BMP-7) in chondrocytes by adenovirus-mediated gene transfer leads to increased matrix synthesis and cartilage-like tissue formation in vitro. In this context we hypothesized that implantation of genetically modified chondrocytes expressing BMP-7 would accelerate the formation of hyaline-like repair tissue in an equine model of cartilage defect repair. Methods: Chondrocyt...
Osteon pullout in the equine third metacarpal bone: effects of ex vivo fatigue. An important concept in bone mechanics is that osteons influence mechanical properties in several ways, including contributing to toughness and fatigue strength by debonding from the interstitial matrix so as to "bridge" developing cracks. Observations of "pulled out" osteons on fracture surfaces are thought to be indicative of such behavior. We tested the hypothesis that osteon pullout varies with mode of loading (fatigue vs. monotonic), cortical region, elastic modulus, and fatigue life. Mid-diaphseal beams from the dorsal, medial, and lateral regions of the equine third metacarpal bone were...
Parathyroid hormone-related peptide and indian hedgehog expression patterns in naturally acquired equine osteochondrosis. Early changes in parathyroid hormone-related peptide (PTH-rP) and Indian hedgehog (Ihh) expression were examined in equine articular osteochondrosis (OC) as a model of a naturally acquired dyschondroplasia. Cartilage was harvested from OC-affected femoropatellar or scapulohumeral joints from immature horses and normal control horses of similar age. PTH-rP expression levels were assessed by semi-quantitative PCR, in situ hybridization, and immunohistochemistry. Ihh protein expression levels were assessed by immunohistochemistry. Elevated PTH-rP protein and mRNA expression were identified in the...
Excessive degradation of type II collagen in articular cartilage in equine osteochondrosis. Articular osteochondrosis (OCD) occurs in both man and animals. The etiology remains to be determined. Studies of OCD lesions in animals may provide clues as to its pathogenesis. The aim of our study was to determine whether there was evidence for increased degradation namely proteoglycan (PG) release and type II collagen cleavage in articular cartilage harvested from OCD lesions. We examined ex vivo explants at post-mortem from equine OCD lesions and macroscopically normal site and age matched cartilage. These were cultured over a 10 day period in serum-free medium. Type II collagen cleavage ...
Insulin-like growth factor-I improves cellular and molecular aspects of healing in a collagenase-induced model of flexor tendinitis. Flexor tendinitis is a common and debilitating injury of elite and recreational athletes. Healing may be improved through intratendinous injection of insulin-like growth factor-I (IGF-I), which has been shown in vitro to stimulate mitogenesis and enhance tendon matrix production. This study investigated the effects of intratendinous injection of IGF-I on tendon healing in an equine model of flexor tendinitis. Collagenase-induced lesions were created in the tensile region of theflexor digitorum superficialis tendon of both forelimbs of eight horses. Treated tendons were injected with 2 microg r...
Stiff and strong compressive properties are associated with brittle post-yield behavior in equine compact bone material. Our hypothesis was that post-yield mechanical behavior of compact bone material in compression, defined as the stress, strain, or energy absorbed between 0.2% strain-offset and the point of maximum stress, is correlated with material density, modulus, strength, histomorphometric evidence of remodeling, and post-failure gross specimen morphology. Post-yield behavior of compact bone material from the third metacarpal bone of 10 horses, ages 5 months to 20 years, was investigated using single-load compression-to-failure. The post-yield stress, strain, and absorbed energy were compared with the co...
Subchondral bone thickness, hardness and remodelling are influenced by short-term exercise in a site-specific manner. It was hypothesised that subchondral bone thickness, hardness and remodelling are influenced by exercise intensity, and by location within a joint. Dorsal carpal osteochondral injury is a major cause of lameness in horses undergoing high intensity training. This project aimed to determine the subchondral bone thickness, formation, resorption and hardness at sites with high and low incidence of pathology in 2 year-old horses undergoing 19 weeks high intensity treadmill training or low intensity exercise, and to compare these factors between exercise groups. Dorsal and palmar test sites were ide...
The prediction of stress fractures using a ‘stressed volume’ concept. This paper addresses an anomaly which exists in the current literature regarding stress fractures. Analysis of the data on fatigue strength of bone samples in vitro would conclude that these fractures should never occur at the strain levels known to occur in vivo. This anomaly can be resolved by including in the analysis the effect of stressed volume, whereby larger volumes of material are expected to have worse fatigue properties. A Weibull analysis was used to predict the probability of failure, Pf; this was an upper-bound prediction because it did not include the effects of remodelling and ...
Corticosteroids alter the differentiated phenotype of articular chondrocytes. Experimental evidence suggests that recommended dosages of some corticosteroids used clinically as antiinflammatory agents for treating arthropathies damage articular cartilage, but low dosages may be chondroprotective. The purpose of this study was to evaluate how different concentrations of methylprednisolone affect chondrocyte function and viability. Articular cartilage and chondrocytes were obtained from young adult horses, 1.5-3.5 years of age. Corticosteroid-induced changes in collagen expression were studied at the transcriptional level by Northern blot analyses and at the translational...
Insulin-like growth factor-I gene expression patterns during spontaneous repair of acute articular cartilage injury. This 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 proteoglycan deposition,...
Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor-beta1 in monolayer and insulin-like growth factor-I in a three-dimensional matrix. This study evaluated chondrogenesis of mesenchymal progenitor stem cells (MSCs) cultured initially under pre-confluent monolayer conditions exposed to transforming growth factor-beta1 (TGF-beta1), and subsequently in three-dimensional cultures containing insulin-like growth factor I (IGF-I). Bone marrow aspirates and chondrocytes were obtained from horses and cultured in monolayer with 0 or 5 ng of TGF-beta 1 per ml of medium for 6 days. TGF-beta 1 treated and untreated cultures were distributed to three-dimensional fibrin disks containing 0 or 100 ng of IGF-I per ml of medium to establish fou...
Use of synovial fluid markers of cartilage synthesis and turnover to study effects of repeated intra-articular administration of methylprednisolone acetate on articular cartilage in vivo. In vivo the effects of intra-articular (IA) corticosteroids on articular cartilage remain controversial. This study was designed to examine this issue using synovial fluid (SF) markers of cartilage metabolism. Paired radiocarpal joints, without clinical or radiographic signs of joint disease, were studied in 10 adult horses. Aseptic arthrocentesis was performed weekly for 13 weeks. IA injections of methylprednisolone acetate (MPA) into the treatment joint and the vehicle into the control joint were performed at weeks 3, 5 and 7. We used radioimmunoassays on SF samples which measure a keratan s...
Alterations in cartilage type-II procollagen and aggrecan contents in synovial fluid in equine osteochondrosis. The etiology and pathophysiology of osteochondrosis remain poorly understood because it is difficult to obtain material from lesions in the early stage of this disease and because there is no satisfactory experimental animal model. We wished to determine whether there are changes in articular cartilage turnover in equine osteochondrosis, which closely resembles the human disease, by assaying cartilage matrix molecules in synovial fluids. We used immunoassays that measure a keratan sulfate epitope and the epitope 846 on the cartilage proteoglycan aggrecan and the C-propeptide of cartilage type-...
Exercise affects the mechanical properties and histological appearance of equine articular cartilage. Dorsal carpal osteochondral injury is a major cause of reduced performance in horses undergoing high-intensity training. It was hypothesised that the mechanical behaviour and histology of cartilage are influenced by the intensity of exercise and by location within a joint. Relationships between histology and mechanical behaviour were identified in 2-year-old horses undergoing 19 weeks of high-intensity treadmill training or low-intensity exercise and then compared between groups. Dorsal and palmar test sites were identified on radial, intermediate, and third carpal articular surfaces after eut...
Exercise of young thoroughbred horses increases impact strength of the third metacarpal bone. Exercise can have a profound effect on bone mass, but little is known of its effect on bone's material properties. In this experiment, our hypothesis was that a large difference in the training regimen of young thoroughbreds would produce a measurable difference in the mechanical properties of their bone material. When they were about 19 months old, eight thoroughbred racehorses were given one of two exercise regimens that lasted for 19 weeks: four horses (controls) were walked for 40 minutes a day but had no other exercise, and the remaining four (exercised) were additionally trotted for 20 m...
In vitro fatigue behavior of the equine third metacarpus: remodeling and microcrack damage analysis. We studied remodeling and microcrack damage in specimens of Thoroughbred racehorse third metacarpal bone that had been subjected to monotonic or fatigue failure. We asked three questions. What effects does mechanical loading have on histologically observable microcrack damage? Are there regional variations in remodeling of the equine cannon bone, and do these variations correlate with mechanical properties? To what extent are remodeling and microcrack damage age-dependent? Machined beams from the medial, lateral, and dorsal cortices were loaded to fracture in four-point bending monotonically, ...
Biomechanical properties of third carpal articular cartilage in exercised and nonexercised horses. The relevance of site and exercise on the biomechanical properties of the articular cartilage from the equine third carpal bone were assessed by creep indentation testing. Six horses were exercised for 30 minutes three times weekly. Another six horses were housed in box stalls and were not exercised. At the conclusion of the study, one third carpal bone from each horse was harvested and the KLM biphasic material properties of cartilage were determined at 12 sites. There was a significant (p < 0.01) effect of site but not exercise on the cartilage aggregate modulus, which was significantly l...
Fatigue behavior of the equine third metacarpus: mechanical property analysis. This is the first in a series of experiments to study the fatigue properties of equine cannon (third metacarpal) bone specimens from Thoroughbred racehorses. Monotonic and fatigue tests to failure were performed in four-point bending on diaphyseal specimens in a 37 degrees C saline bath to answer three initial questions. (a) Will a linear variable differential transducer yield the same elastic modulus as strain gauges? (b) Will fatigue results depend on whether the periosteal or endosteal side of the beam is in tension? (c) Are there regional variations in the monotonic and fatigue properties ...
Estimation of material properties in the equine metacarpus with use of quantitative computed tomography. The purpose of this study was to investigate the relationships between data obtained from quantitative computed tomography and mechanical properties in the equine metacarpus, as measured in vitro in bone specimens. Three hundred and fifty-five bone specimens from the metacarpi of 10 horses were machined into right cylinders aligned with the long axis of the bone. A computed tomographic scan of the specimens, along with a Cann-Genant K2HPO4 calibration standard, was obtained. The specimens then were compressed to failure, and the elastic modulus, yield stress, yield strain, strain energy densit...
Chondrocyte-fibrin matrix transplants for resurfacing extensive articular cartilage defects. Cartilage resurfacing by chondrocyte implantation, with fibrin used as a vehicle, was examined in large (12 mm) full-thickness articular cartilage defects in horses. Articular chondrocytes, isolated from a 9-day-old foal, were mixed with fibrinogen and injected with thrombin, in a 1:1 mixture, into 12 mm circular defects on the lateral trochlea of the distal femur of eight normal horses. The contralateral femoropatellar (knee) joint served as a control in which the defect was left empty. Synovial fluid from the femoropatellar joints was sampled on days 0, 4, 7, 30, 120, and 240 postoperatively...
Effects of exercise and polysulfated glycosaminoglycan on repair of articular cartilage defects in the equine carpus. Our aim was to determine if mild to moderate postoperative exercise and intra-articular polysulfated glycosaminoglycan result in improved repair of large, experimentally induced osteochondral defects in a weight-bearing surface of equine joints. Arthroscopic debridement was used to produce full-thickness defects in a weight-bearing area of the radial carpal bones in 18 ponies. The ponies were randomly assigned to two groups balanced for age: nine animals in the exercise and nine in the no exercise group. Six ponies in each group were medicated weekly for 5 weeks with an intra-articular injecti...
Pulsed magnetic fields improve osteoblast activity during the repair of an experimental osseous defect. The influence of pulsed low-frequency electromagnetic fields (PEMFs) on bone formation was investigated in studies of the healing process of transcortical holes, bored at the diaphyseal region of metacarpal bones of six adult horses, exposed for 30 days to PEMFs (28 G peak amplitude, 1.3 ms rise time, and 75 Hz repetition rate). A pair of Helmholtz coils, continuously powered by a pulse generator, was applied for 30 days to the left metacarpal bone, through which two holes, of equal diameter and depth, had been bored at the diaphyseal region. Two equal holes, bored at the same level in the rig...