Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CARTILAGE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMed2006

Quantitative ultrasound imaging detects degenerative changes in articular cartilage surface and subchondral bone.

Previous studies have suggested that quantitative ultrasound imaging could sensitively diagnose degeneration of the articular surface and changes in the subchondral bone during the development of osteoarthrosis (OA). We have recently introduced a new parameter, ultrasound roughness index (URI), for the quantification of cartilage surface roughness, and successfully tested it with normal and experimentally degraded articular surfaces. In this in vitro study, the applicability of URI was tested in bovine cartilage samples with spontaneously developed tissue degeneration. Simultaneously, we studied the sensitivity of quantitative ultrasound imaging to detect degenerative changes in the cartilage-bone interface. For reference, histological degenerative grade of the cartilage samples was determined. Mechanical reference measurements were also conducted. Cartilage surface roughness (URI) was significantly (p<0.05) higher in histologically degenerated samples with inferior mechanical properties. Ultrasound reflection at the cartilage-bone interface was also significantly (p<0.05) increased in degenerated samples. Furthermore, it was quantitatively confirmed that ultrasound attenuation in the overlying cartilage significantly affects the measured ultrasound reflection values from the cartilage-bone interface. To conclude, the combined ultrasound measurement of the cartilage surface roughness and ultrasound reflection at the cartilage-bone interface complement each other, and may together enable more sensitive and quantitative diagnosis of early OA or follow up after surgical cartilage repair.

Algorithms↗
PubMed1996

Cartilage-bone replacement in endochondral ossification of mandibular condylar heads in young beagle dogs.

The cellular mechanisms of cartilage-bone replacement in endochondral bone formation, in mandibular condylar heads, are poorly understood. In particular, there is no definitive evidence indicating whether cartilage is resorbed by so-called chondroclasts. Using 3-week-old male beagle dogs, we examined the cartilage-bone replacement processes in mandibular condylar heads by means of light and electron microscopy. Calcification of the cartilage matrix occurred in the central area of the longitudinal septa but not in thin transverse septa. Chondrocytic lacunae were opened by the removal of transverse septa by perivascular rough-surfaced endoplasmic reticulum (RER)-rich mononuclear cells. These cells also phagocytosed calcified cartilage fragments in the surface layer of longitudinal septa. Shortly thereafter, a thin bone layer was deposited on the remaining longitudinal septa by invading osteoblasts. Preosteoclastic multinucleated cells in lacunar canals developed neither ruffled borders nor clear zones in the cartilage matrix, but once the bone layer had been deposited on the remaining cartilage, these structures formed. Our results suggest that the cartilage-bone replacement in mandibular condylar heads involves four sequential processes: 1) degradation of the transverse septal cartilage by RER-rich mononuclear cells, 2) phagocytosis of calcified cartilage fragments in the longitudinal septa by these cells, 3) bone deposition of the remaining longitudinal septa, and 4) degradation of both bone and calcified cartilage by differentiated osteoclasts.

Animals↗
PubMed2005

The clinical correlates of articular cartilage defects in symptomatic knee osteoarthritis: a prospective study.

OBJECTIVES: To determine whether articular cartilage defects are associated with cartilage loss and joint replacement in subjects with symptomatic knee osteoarthritis (OA). METHODS: One hundred and seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of their dominant knee at baseline and 2 yr later. Cartilage defects were identified as prevalent (defect score > or =2) in each knee compartment. Occurrence of joint replacement by 4 yr was documented. RESULTS: Cartilage defects were present in 81% of medial, 64% of lateral tibiofemoral compartments and 55% of patellar cartilages. Annual patellar cartilage loss was highest in those with defects compared with no defects (5.5% vs 3.2%, P = 0.01). Tibial cartilage loss was not associated with defects in the medial (4.6% vs 5.8%, P = 0.42) or lateral (4.7% vs 6.5%, P = 0.21) tibial cartilages. Higher total cartilage defect scores (8-15) were associated with a 6.0-fold increased risk of joint replacement over 4 yr compared with those with lower scores (2-7) (95% confidence interval 1.6, 22.3), independently of potential confounders. CONCLUSIONS: Articular cartilage defects are associated with disease severity in knee OA and predict patellar cartilage loss and knee replacement.

Aged↗
PubMed1994

The fate of fresh and preserved, noncrushed and crushed autogenous cartilage in the rabbit model.

This study was conducted to investigate volume retention and chondrocyte survival rate in autogenous fresh noncrushed, fresh crushed, preserved noncrushed, and preserved crushed cartilage grafts in rabbits. During the first phase of this investigation, cartilage was harvested from the right ear of 20 New Zealand white rabbits, then preserved. Four months later during the second phase, two 6-mm discs of previously harvested and preserved cartilage, one crushed and one noncrushed, were applied to the right ear. At the same time, two 6-mm discs of fresh cartilage graft were harvested from the left ear and then placed at a higher level on the same side, one crushed and one noncrushed. Three months after implantation, the rabbits were sacrificed and the grafts were evaluated. The preserved noncrushed cartilage retained 91.34% of the volume (SD = 2.46). Although most of the chondrocytes were nonviable, vascular ingrowth occurred with a significant repopulation of chondrocytes peripherally, in association with vascular endothelial ingrowth. The preserved crushed cartilage retained 74.19% of the volume (SD = 3.06). Most of the original chondrocytes were lost, but vascular ingrowth did occur and some osteoid formation occurred on the crushed cartilages. All chondrocytes on the fresh noncrushed cartilage grafts were viable and the grafts retained 94.54% of the volume (SD = 2.46). Crushed fresh cartilage retained 69.73% of its volume and the amount of viable chondrocytes ranged from 70% to 90% in the specimens evaluated (SD = 5.15). Although there is no question that noncrushed cartilage is superior, crushed cartilage can be used with a fair degree of predictability to attain the aesthetic goal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Visualization of collagenase-induced cartilage degradation using NMR microscopy.

RATIONALE AND OBJECTIVES: There is an ongoing discussion about the role of collagenase as a specific cartilage-degrading enzyme in the course of osteoarthritis. Using NMR microscopy, the influence of collagenase on the cartilage structure was investigated. METHODS: High-resolution MR imaging investigations were performed at 7.1 Tesla to study the influence of collagenase on the cartilage structure of pig femoral condyles. Two different contrast agents (polylysine-Gd-DTPA and liposome-entrapped contrast agents) were tested to improve the NMR microscopic visualization of the damaged cartilage regions. RESULTS: The NMR microscopic investigations showed that collagenase affects only the cartilage surface. Changes within the cartilage layer were not detected. However, after the application of specific contrast agents, it was possible to detect with great sensitivity collagenase-induced damage to the collagen network on the cartilage surface and the superficial cartilage zones. The application of liposome-entrapped contrast agents improved the visualization of the collagenase-degraded superficial cartilage zone. CONCLUSIONS: These findings could be of great importance when estimating the state of the articular cartilage. The degree of fibrillation of the cartilage surface in the course of osteoarthritic disease can be visualized by MR tomography with a high degree of sensitivity.

Animals↗
PubMed1999

Anatomic reconstruction of the nasal tip cartilages in secondary and reconstructive rhinoplasty.

Most techniques for secondary rhinoplasty assume that useful residual remnants of the tip cartilages remain, but frequently the alar cartilages are missing--unilaterally, bilaterally, completely, or incompletely--with loss of the lateral crura, middle crura, and parts of the medial crura. In such severe cases, excision of scar tissue and the residual alar remnants and their replacement with nonanatomic tip grafts have been recommended. Multiple solid, bruised, or crushed cartilage fragments are positioned in a closed pocket or solid shield-shaped grafts are fixed with sutures during an open rhinoplasty. These onlay filler grafts only increase tip projection and definition. Associated tip abnormalities (alar rim notching, columellar retraction, nostril distortion) are not addressed. Problems with graft visibility, an unnatural appearance, or malposition have been noted. Fortunately, techniques useful in reconstructive rhinoplasty can be applied to severe cosmetic secondary deformities. Anatomic cartilage replacements similar in shape, bulk, and position to normal alar cartilages can be fashioned from septal, ear, and rib cartilage, fixed to the residual medial crura and/or a columellar strut, and bent backward to restore the normal skeletal framework of the tip. During an open rhinoplasty, a fabricated and rigid framework is designed to replace the missing medial, middle, or lateral crus of one or both alar cartilages. The entire alar tripod is recreated. These anatomic alar cartilage reconstructive grafts create tip definition and projection, fill the lobule and restore the expected lateral convexity, position the columella and establish columellar length, secure and position the alar rim, and brace the external valve against collapse, support the vestibular lining, and restore a nostril shape. The anatomic form and function of the nasal tip is restored. This technique is recommended when alar cartilages are significantly destroyed or absent in secondary or reconstructive rhinoplasty and the alar remnants are insufficient for repair. Anatomically designed alar cartilage replacements allow an aesthetically structured skeleton to contour the overlying skin envelope. Problems with displacement are minimized by graft fixation. Graft visibility is used to the surgeon's advantage. A rigidly supported framework with a nasal shape can mold a covering forehead flap or the scarred tip skin of a secondary rhinoplasty and create a result that may approach normal. Anatomic alar cartilage reconstructions were used in eight reconstructive and eight secondary rhinoplasties in the last 5 years. Their use in the repair of postrhinoplasty deformities is emphasized.

Cartilage↗
PubMed2003

Controlling incision-induced distortion of nasal septal cartilage: a model to predict the effect of scoring of rabbit septa.

Cartilage can be shaped by scoring. In an exploratory study in living adult animals, this phenomenon was demonstrated in cartilage of the nasal septum. Bending was observed immediately after superficial scoring of the cartilage surface, and the cartilage always warped in the direction away from the scored side. The scored piece of cartilage still showed its initially distorted shape 10 weeks after primary surgery. In ex vivo experiments, a clear relation between incision depth and bending of septal cartilage was observed. Under these controlled conditions, the variation between different septa was small. Deformation of the septal specimens was increased by introducing single superficial incisions deepening to half the thickness of the cartilage. A positive correlation between incision depth and bending was demonstrated. A model was used to accurately predict the degree of bending of the cartilage after making an incision of a particular depth. Hence, the effect of cartilage scoring can be predicted. Because the results of this controlled study showed excellent reproducibility for different septa, it is expected that this model can be extrapolated to human nasal septum cartilage. This would enable the surgeon to better predict the result of cartilage scoring, either preoperatively or perioperatively.

Animals↗
PubMed2006

A new method of costal cartilage harvest for total auricular reconstruction: part I. Avoidance and prevention of intraoperative and postoperative complications and problems.

BACKGROUND: The occurrence of chest wall deformity is not dependent on the amount of costal cartilage harvested but results from the method of costal cartilage harvest. Therefore, the authors developed a new method of costal cartilage harvest where the perichondrium is left completely intact at the donor site and the remaining costal cartilage after fabrication of the three-dimensional costal cartilage framework is returned to the perichondrial pocket to fill the dead space formed. By leaving the perichondrium completely intact, the most ideal environmental condition for regeneration of cartilage is attained. METHODS: The costal cartilages are harvested en bloc with the perichondrium left completely intact at the donor site. After fabrication of the three-dimensional frame, the remaining costal cartilage is cut into small blocks that act as spacers to fill the dead space formed in the perichondrial pocket. RESULTS: The findings of the authors' study involving over 270 cases performed with the new method of costal cartilage harvest revealed that there were absolutely no postoperative chest wall deformities identified, and there was a significant decrease in intraoperative complications. CONCLUSION: The authors' study revealed that the new method of costal cartilage harvest plays an important role in the regeneration of cartilage and in the prevention and avoidance of postoperative chest wall deformity.

Adolescent↗
PubMedDate not supplied

Cell origin in experimental repair of cricoid cartilage defects treated with recombinant human bone morphogenetic protein-2.

We determined the origin of new cartilage and new bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) at the site of cricoid cartilage defects in rabbits randomly divided into eight groups. The cricoid cartilage was split vertically along the anterior midline and a strip was excised from the anterior part of the cricoid cartilage in all rabbits. The perichondrium from the anterior part of the cricoid cartilage was trimmed off in four groups; two groups treated with rhBMP-2 and two control groups. In four other groups, the anterior perichondrium was detached and used as a flap with two groups treated with rhBMP-2 and two groups serving as controls. The rabbits were killed 1 week or 4 weeks after surgery. The larynges were removed, fixed and sectioned, and the sections were stained for light microscopy using various cytochemical and immunological techniques. New cartilage was only present close to the host perichondrium adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone was present 4 weeks after surgery, although calcified matrix and alkaline phosphatase activity could be detected at the site of cricoid defects as early as 1 week after surgery. The cell proliferation marker Ki-67 was strongly expressed in granulation tissue and bone marrow, and it was moderately expressed in muscles adjacent to the cricoid cartilage in rhBMP-2-treated specimens. BMP receptors were strongly expressed in cartilage and moderately expressed in adjacent muscles. We conclude that new cartilage originates from the mesenchymal progenitor cells of host perichondrium adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone may originate from local muscle.

Administration, Topical↗
PubMed2006

The effects of exercise on human articular cartilage.

The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass.

Adaptation, Physiological↗
PubMed1980

Effect of homologous synovial membrane on adult human articular cartilage in organ culture, and failure to influence it with D-penicillamine.

Adult human articular cartilage has been maintained in organ culture for 8 days, and the culture medium, which was changed on alternate days, was pooled. Normal and rheumatoid cartilage was obtained from patients and 4 types of culture were prepared: (1) cartilage alone; (2) cartilage + D-penicillamine; (3) cartilage + homologous synovium; (4) cartilage, synovium, and D-penicillamine. The hexosamines and hexuronic acid were measured in the cartilage explants and in the medium. The quantity released was divided by the amount measured in the original cartilage explant and the different culture variables were compared. D-penicillamine did not alter the release of cartilage proteoglycan, but the addition of synovium did. The rheumatoid cartilage released significantly more proteoglycan than normal cartilage whether or not homologous synovium was present.

Adult↗
PubMed2006

Delayed gadolinium-enhanced MR to determine glycosaminoglycan concentration in reparative cartilage after autologous chondrocyte implantation: preliminary results.

PURPOSE: To prospectively evaluate delayed gadolinium-enhanced magnetic resonance (MR) imaging of cartilage for assessment of glycosaminoglycan (GAG) concentration in reparative cartilage after autologous chondrocyte implantation (ACI). MATERIALS AND METHODS: The study was approved by the ethics review committee of the National Institute of Radiological Sciences, and informed consent was obtained from all patients. The study group comprised nine knees of nine patients (six male, three female; mean age at ACI, 21.2 years +/- 7.5 [standard deviation]; age range, 13-35 years) who had undergone ACI and second-look arthroscopy with biopsy. MR imaging was performed at 1.5 T before and after intravenous injection of anionic gadopentetate dimeglumine. The precontrast R1 (R1(pre)), postcontrast R1 (R1(post)), and difference between R1(pre) and R1(post) (DeltaR1) were measured in reparative cartilage and normal cartilage. GAG concentrations in cartilage biopsy specimens were measured by using high-performance liquid chromatography. To evaluate delayed gadolinium-enhanced MR imaging of cartilage for assessment of GAG concentration, the authors defined the relative R1(pre), relative R1(post), and relative DeltaR1 (ie, R1(pre), R1(post), or DeltaR1, respectively, in reparative cartilage divided by that in normal cartilage) and the relative GAG concentration (ie, GAG concentration in reparative cartilage divided by that in normal cartilage). They then examined the relationships between relative R1(pre), relative R1(post), relative DeltaR1, and relative GAG by using correlation analysis. RESULTS: A significant correlation between relative DeltaR1 and relative GAG concentration (r = 0.818, P < .05) was observed. However, no significant correlation between relative R1(pre) and relative GAG concentration (r = 0.010, P = .983) or between relative R1(post) and relative GAG concentration (r = 0.660, P = .106) was observed. CONCLUSION: Study results indicate that pre- and postcontrast imaging is necessary for delayed gadolinium-enhanced MR imaging evaluation of reparative cartilage after ACI.

Adolescent↗
PubMed1997

Aggrecan degradation in human cartilage. Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints.

To examine the activity of matrix metalloproteinases (MMPs) and aggrecanase in control and diseased human articular cartilage, metabolic fragments of aggrecan were detected with monospecific antipeptide antibodies. The distribution and quantity of MMP-generated aggrecan G1 fragments terminating in VDIPEN341 were compared with the distribution of aggrecanase-generated G1 fragments terminating in NITEGE373. Both types of G1 fragments were isolated from osteoarthritic cartilage. The sizes were consistent with a single enzymatic cleavage in the interglobular domain region, with no further proteolytic processing of these fragments. Both neoepitopes were also detected by immunohistochemistry in articular cartilage from patients undergoing joint replacement for osteoarthritis (OA), rheumatoid arthritis (RA), and in cartilage from adults with no known joint disease. In control specimens, the staining intensity for both G1 fragments increased with age, with little staining in cartilage from 22-wk-old fetal samples. There was also an increase with age in the extracted amount of MMP-generated neoepitope in relation to both aggrecan and collagen content, confirming the immunohistochemical results. After the age of 20-30 yr this relationship remained at a steady state. The staining for the MMP-generated epitope was most marked in control cartilage exhibiting histological signs of damage, whereas intense staining for the aggrecanase-generated fragment was often noted in adult cartilage lacking overt histological damage. Intense staining for both neoepitopes appeared in the more severely fibrillated, superficial region of the tissue. Intense immunostaining for both VDIPEN- and NITEGE- neoepitopes was also detected in joint cartilage from patients with OA or RA. Cartilage in these specimens was significantly more degraded and high levels of staining for both epitopes was always seen in areas with extensive cartilage damage. The levels of extracted VDIPEN neoepitope relative to collagen or aggrecan in both OA and RA samples were similar to those seen in age-matched control specimens. Immunostaining for both types of aggrecan fragments was seen surrounding the cells but also further removed in the interterritorial matrix. In some regions of the tissue, both neoepitopes were found while in others only one was detected. Thus, generation and/or turnover of these specific catabolic aggrecan fragments is not necessarily coordinated. Our results are consistent with the presence in both normal and arthritic joint cartilage of proteolytic activity against aggrecan based on both classical MMPs and "aggrecanase."

Adolescent↗
PubMed1985

Homologous and heterologous growth hormones fail to stimulate avian cartilage growth in vitro.

Recent reports that GH has a direct effect on growing cartilage have raised questions as to the role of somatomedins (Sm) in cartilage growth. To test the hypothesis that GH directly stimulates cartilage growth, we added homologous and heterologous GHs to organ cultures of embryonic chick pelvic cartilage. Pelvic rudiments from 9-day-old chick embryos were incubated in serum-free medium for 3 days in medium alone or medium containing chicken GH, turkey GH, bovine GH, human GH, and bovine GH produced by recombinant DNA methodology. None of the GH preparations studied stimulated avian cartilage growth in vitro. However, cartilage wet weight increased in response to sera from normal and growth hormone-treated hypophysectomized rats. In addition, 20 ng/ml purified Sm-C caused a 78% increase in cartilage weight above that of cartilage incubated in medium alone. Insulin also caused an increase in cartilage weight, but in concentrations 50,000-100,000 times that of Sm-C. Our studies demonstrate that homologous and heterologous GH have no effect on growing avian cartilage and support the hypothesis that Sm directly mediate cartilage growth.

Animals↗
PubMed2005

A modeling framework to estimate patellofemoral joint cartilage stress in vivo.

PURPOSE: Patellofemoral (PF) pain is common among athletes and may be caused by increased subchondral bone stress as a result of increased stress in the cartilage of the femur or patella. This article presents a modeling pipeline to estimate in vivo cartilage stress in the PF joint. METHODS: The modeling pipeline uses the finite element method to calculate stresses and strains in the PF joint cartilage. Model inputs include an accurate geometrical representation of the bones and cartilage from magnetic resonance imaging (MRI), cartilage material properties, and an estimate of muscle forces from an EMG-driven musculoskeletal model. Validation is performed using PF joint contact area and patellar orientation measured from upright, weight-bearing MRI. Preliminary data from an active, pain-free subject illustrate the modeling pipeline to calculate cartilage stress during a static squat. RESULTS: The quasistatic finite element simulation reproduced the orientation of the patella to within 2.1 mm and predicted the PF joint contact area to within 2.3%. Octahedral shear stresses were highest in the central, lateral aspect of the patella cartilage with a peak of 2.5 MPa. The corresponding stresses in the femoral cartilage reached only 2.0 MPa. However, peak hydrostatic pressures were higher within the femoral cartilage (3.5 MPa) than the patellar cartilage (2.3 MPa). CONCLUSION: The methods presented in this article offer a novel approach to calculate PF joint cartilage stress in vivo. Future efforts will use this modeling pipeline to further our knowledge of PF pain and potential rehabilitation strategies.

Cartilage↗
PubMed1981

Avulsion of the upper lateral cartilage: etiology, diagnosis, surgical anatomy and management.

Relatively little has been published about upper lateral cartilage abnormalities, trauma, and management in rhinoplastic literature. In this paper we would like to present a relatively common problem seen either by trauma or as a result of rhinoplasty. The upper lateral cartilages are a pair of triangular cartilages, one on each side of the dorsum, which comprise the upper cartilaginous vault with the septum and can be avulsed due to direct trauma. This results in loss of their attachments and resultant healing in a new angulated position. The middle third of the nose, being relatively mobile is less susceptible to trauma than the upper third which is rigid and comprised of bone, and that frequently is the reason for less incidence of avulsion of the upper lateral cartilages compared to fractured nasal bones. The surgical treatment of the structures adjacent to the upper lateral cartilage during the process of rhinoplasty severs many attachments of these cartilages and frequently causes them to be free floating. This may not be recognized and not treated. Lack of appropriate realignment in the normal anatomical position may heal the cartilage in a distorted angulated position. Irrespective of etiology, when distortions of the upper lateral cartilage occur, they may cause significant concavity and "hollowed out" appearance on the side of the avulsion which functionally may impede the nasal airway by encroachment and/or "flutter valve" effect. During inspiration this unsupported upper lateral cartilage may interfere with anatomy, physiology and efficiency of the internal nasal valve function. Avulsion of the upper lateral cartilage is a definite entity and should be recognized and treated appropriately to realign the lateral cartilage in its normal anatomical position for a functional as well as a good cosmetic result.

Adult↗
PubMed2004

Deficiency of insulin receptor substrate-1 impairs skeletal growth through early closure of epiphyseal cartilage.

UNLABELLED: Morphological analyses in and around the epiphyseal cartilage of mice deficient in insulin receptor substrate-1 (IRS-1) showed IRS-1 signaling to be important for skeletal growth by preventing early closure of the epiphyseal cartilage and maintaining the subsequent bone turnover at the primary spongiosa. INTRODUCTION: IRS-1 is an essential molecule for intracellular signaling by IGF-I and insulin, both of which are potent anabolic regulators of cartilage and bone metabolism. To clarify the role of IRS-1 signaling in the skeletal growth, morphological analyses were performed in and around the epiphyseal cartilage of mice deficient in IRS-1 (IRS-1(-/-)), whose limbs and trunk were 20-30% shorter than wildtype (WT) mice. MATERIALS AND METHODS: The epiphyseal cartilage and the primary spongiosa at proximal tibias of homozygous IRS-1(-/-) and WT male littermates were compared using histological, immunohistochemical, enzyme cytohistochemical, ultrastructural, and bone histomorphometrical analyses. RESULTS: In and around the WT epiphyseal cartilage, IRS-1 and insulin-like growth factor (IGF)-1 receptors were widely expressed, whereas IRS-2 was weakly localized in bone cells. Chronological observation revealed that height of the proliferative zone and the size of hypertrophic chondrocytes were decreased in WT mice as a function of age, and these decreases were accelerated in the IRS-1 (-/-) cartilage, whose findings at 12 weeks were similar to those of WT at 24 weeks. In the IRS-1(-/-) cartilage, proliferating chondrocytes with positive proliferating cell nuclear antigen (PCNA) or parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor immunostaining had almost disappeared by 12 weeks. Contrarily, TUNEL+ apoptotic cells were increased in the hypertrophic zone, at the bottom of which most of the chondrocytes were surrounded by the calcified matrix, suggesting the closure of the cartilage. In the primary spongiosa, bone volume, alkaline phosphatase (ALP)+ osteoblasts, TRACP+ osteoclasts, and the osteopontin-positive cement line were markedly decreased. Bone histomorphometrical parameters for both bone formation and resorption were significantly lower in IRS-1(-/-) mice, indicating the suppression of bone turnover. CONCLUSION: The IRS-1(-/-) epiphyseal cartilage exhibited insufficient proliferation of chondrocytes, calcification of hypertrophic chondrocytes, acceleration of apoptosis, and early closure of the growth plate. Thus, the data strongly suggest that IRS-1 signaling is important for the skeletal growth by preventing early closure of the epiphyseal cartilage and by maintaining the subsequent bone turnover at the primary spongiosa.

Animals↗
PubMed2004

Increased VEGF expression in the epiphyseal cartilage after ischemic necrosis of the capital femoral epiphysis.

UNLABELLED: Ischemic injury to the immature femoral head produces epiphyseal cartilage damage and cessation of endochondral ossification. This study suggests that VEGF facilitates the repair of the necrotic epiphyseal cartilage, which is essential for restoration of endochondral ossification and re-establishment of the growth of the immature femoral head after ischemic necrosis. INTRODUCTION: Legg-Calve-Perthes disease (LCPD) is a childhood form of osteonecrosis that produces growth arrest of the secondary center of ossification. The cessation of growth is caused by ischemic damage to the hypertrophic zone of the epiphyseal cartilage where endochondral ossification normally occurs. The role of vascular endothelial growth factor (VEGF) in restoring endochondral ossification in the epiphyseal cartilage after ischemic necrosis was investigated in a piglet model of LCPD because the resumption of normal growth is important for maintaining the spherical shape of the femoral head. MATERIALS AND METHODS: Piglet femoral heads were assessed 24 h to 8 weeks after the surgical induction of ischemia. Western blot analysis, ribonuclease protection assay (RPA), immunohistochemistry, and in situ hybridization were performed. RESULTS: Western blot analysis and RPA showed increased VEGF protein and mRNA expression, respectively, in the epiphyseal cartilage of the infarcted heads compared with the contralateral normal heads. In the normal femoral heads, VEGF-immunoreactivity (VEGF-IR) and transcripts were observed in the hypertrophic zone of the epiphyseal cartilage. In the infarcted heads, VEGF-IR and transcripts were no longer observed in the hypertrophic zone because of diffuse cell death in that zone from ischemia. However, VEGF-IR and transcripts were observed in the proliferative zone above the necrotic hypertrophic zone. At 8 weeks, vascular granulation tissue invasion of the necrotic hypertrophic zone was observed with active resorption of the necrotic cartilage. In some areas where the necrotic cartilage was completely resorbed, restoration of endochondral ossification was observed. In these areas, VEGF transcripts were observed in the newly formed hypertrophic zone. CONCLUSIONS: VEGF expression was increased, and its spatial expression was altered in the epiphyseal cartilage after ischemic necrosis of the immature femoral head. VEGF upregulation in the proliferative zone after ischemic damage may play a role in stimulating vascular invasion and granulation tissue formation in the necrotic hypertrophic zone of the epiphyseal cartilage. This may be an important step toward facilitating the resorption of the necrotic cartilage and restoration of endochondral ossification leading to further growth and development of the femoral head.

Animals↗