Biomedical subjects

D Amiel

Publications and source records attributed to D Amiel.

At least 19 recordsLinked to original sources

PubMed2002

Development and regulation of osteophyte formation during experimental osteoarthritis.

OBJECTIVES: Osteophytes represent areas of new cartilage and bone formation in human and experimentally induced osteoarthritis (OA). The present study addressed the production of nitric oxide (NO), vascular endothelial growth factor (VEGF) and the occurrence of apoptosis during osteophyte formation. DESIGN: Osteophytes in the knee joint of rabbits that developed OA-like lesions following anterior cruciate ligament transection (ACLT) were analysed by histology and immunohistochemistry for NO production, and the presence of VEGF. TUNEL was used to detect DNA fragmentation. RESULTS: At the joint margins in the interface between cortical bone marrow and periosteal lining growth plate-like formations were detectable as early as 4 weeks after ACLT. By 12 weeks after ACLT osteophytes were visible in 100% of femoral condyles and tibial plateaus. Discrete areas with proliferating chondrocytes, hypertrophic chondrocytes, calcified matrix and vascular invasion were observed. VEGF immunoreactivity was most prominent in hypertrophic chondrocytes 9 weeks after ACLT. Nitrotyrosine immunoreactivity was detected in endothelial cells and in some hypertrophic chondrocytes in the calcified zone 4 weeks after ACLT. After 8 and 12 weeks, positive cells were detected in the hypertrophic and calcified zone. TUNEL-positive cells were seen in blood vessels, and among hypertrophic chondrocytes adjacent to the blood vessels 4 weeks after ACLT. The proliferative zone, pre-hypertrophic zone and hypertrophic zone showed only a few TUNEL positive cells. In contrast, 8 weeks and 12 weeks after ACLT, most hypertrophic chondrocytes, but few proliferative chondrocytes showed DNA fragmentation. CONCLUSIONS: Hypertrophic chondrocytes in osteophytes express VEGF and this can promote vascular invasion of cartilage. The presence of TUNEL-positive cells shows a similar distribution as nitrotyrosine immunoreactivity during all phases of osteophyte development, suggesting that NO production and chondrocyte death are related events in osteophyte formation.

Animals↗

PubMed2002

Subchondral bone of the human knee joint in aging and osteoarthritis.

OBJECTIVE: Although most research investigating the pathogenesis of osteoarthritis (OA) has focused on cartilage, it has been suggested that the subchondral bone (SCB) plays an important role in the development of OA. The relationships between aging, severity of OA change and the SCB thickness and density in the human knee joint specimens from a wide range of ages were examined. METHODS: One hundred forty knee joints from 72 individuals (25 females, 45 males and 2 unknowns; average age 54.8 years, range 17 to 91 years) were obtained. The surface of the articular cartilage of both the femur and tibia was evaluated for gross morphological changes with a 4-point grading scale. The lateral and medial femoral condyles were cut along a sagittal plane and the tibia along a coronal plane to make bone and cartilage strip specimens. The strips were X-rayed onto mammography film and then scanned into a computer for assessment of SCB thickness and density using image analysis software. RESULTS: Medial tibial SCB thickness was significantly lower among the elderly (age>69 years) than among the young (age<40) or the middle-aged (40 to 69) (P< 0.001 via ANOVA). Lateral tibial SCB thickness also showed the same trend of decreasing thickness with increasing age, but differences between age groups were not statistically significant. Tibial SCB thicknesses were significantly lower in arthritic grades compared to normal grades (P=0.008 in lateral and 0.017 in medial via ANOVA); in contrast, no significant differences between normal and arthritic were found in femoral SCB thicknesses. The arthritic group tended to have lower SCB densities than the normal group, but this was statistically significant in only the lateral femoral condyle. CONCLUSIONS: The results obtained in the present study are not consistent with generally accepted notions of the relationship between subchondral bone thickness or density and OA. Subchondral bone changes are not etiologic for OA but, more likely, are secondary to loss of articular cartilage which precedes the appearance of subchondral sclerosis.

Adolescent↗

PubMed2001

Hyaluronan suppressed nitric oxide production in the meniscus and synovium of rabbit osteoarthritis model.

Nitric oxide (NO) plays an important role in cartilage degeneration, and NO donors induce meniscus degeneration and synovium inflammation. This study evaluated the effect of intraarticular injections of hyaluronan (HA) on NO production in meniscus and synovium using an experimental osteoarthritis (OA) model. Thirty-six New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT), and were divided into three groups. Four weeks after ACLT, the HA group started to receive intraarticular HA injections once a week for 5 weeks; the vehicle group started to receive the carrier of HA; and the no injection group, no treatment. All ACLT knees were harvested at the 9th week. Meniscus and synovium sections were examined by immunohistochemistry for nitrotyrosine. The pieces of these two tissues were cultured for 24 h. Culture supernatants were analyzed for nitrite concentration. The amount of NO produced by the meniscus was much larger than that produced by the synovium. NO productions in the meniscus and synovium of the HA group were significantly lower than those of the other groups. The results suggest that the inhibition of NO production in meniscus and synovium might be a part of the mechanism of the therapeutic effect of HA on OA.

Animals↗

PubMed2001

Chondrocyte apoptosis and regional differential expression of nitric oxide in the medial meniscus following partial meniscectomy.

Partial medial meniscectomy leads to tibial articular cartilage degeneration. Nitric oxide (NO) production increases with the development of osteoarthritis (OA) and has been shown to have a catabolic effect on chondrocytes. Since distribution of chondrocytic and fibroblastic cell types within the total cell population comprising meniscus is region-specific, we compared NO production in the peripheral and central regions of the medial meniscus 12 weeks after partial medial meniscectomy and assessed chondrocyte apoptosis and NO production in the tibial articular cartilage. Additionally, transcriptional gene expression of inducible nitric oxide synthetase (iNOS) and immunohistochemical staining of nitrotyrosine were examined. The results showed that following partial medial meniscectomy, NO production in the central region of the medial meniscus and in the tibial articular cartilage were significantly higher than respective NO levels in normal and sham-operated controls. Reverse transcription polymerase chain reaction (RT-PCR) revealed a high transcriptional expression of the iNOS gene in the central region of the meniscus and in tibial articular cartilage following partial medial meniscectomy. Nitrotyrosine immunoreactivity was prominent in the central region of the medial meniscus and in the deep layer of the tibial articular cartilage and apoptotic cells were also detected in situ in the superficial zone of the tibial articular cartilage and central regions of the medial meniscus following partial medial meniscectomy. These observations suggest that the central region of the meniscus is responsible for NO synthesis associated with apoptosis in both meniscal and articular cartilage cells following partial meniscectomy.

Animals↗

PubMed2001

A morphologic, biochemical, and biomechanical assessment of short-term effects of osteochondral autograft plug transfer in an animal model.

PURPOSE: The objective of this study was to assess the short-term changes that occur after an osteochondral autograft plug transfer from the femoral trochlea to the medial femoral condyle in a goat model. TYPE OF STUDY: Articular cartilage repair animal study. METHODS: Six adult male goats were used in this study. Two 4.5-mm osteochondral plugs were transferred from the superolateral femoral trochlea to 2 recipient sites in the central portion of the medial femoral condyle for a survival period of 12 weeks. Postmortem, the global effects of the procedure were assessed by gross morphologic inspection and by analyzing the synovial DNA for inflammatory response. The recipient sites were also evaluated histologically and biomechanically. Metabolic activity was determined by (35)SO(4) uptake, and viability was assessed using a live/dead stain and by confocal laser microscopy. RESULTS: There was no evidence of significant gross morphologic or histologic changes in the operative knee as a result of the osteochondral donor or recipient sites. The patella, tibial plateau, and medial meniscus did not show any increased degenerative changes as a result of articulating against the donor or recipient sites of the osteochondral autografts. Analysis of synovial DNA revealed no inflammatory response. Biomechanically, 6- to 7-fold greater stiffness was noted in the cartilage of the transferred plugs compared with the control medial femoral condyle. Furthermore, on histologic examination, the healing subchondral bone interface at the recipient site had increased density. Glycosaminoglycan synthesis as determined by (35)SO(4) uptake was upregulated in the transplanted cartilage plug relative to the contralateral control, showing a repair response at the site of implantation. And finally, confocal microscopy showed 95% viability of the transferred plugs in the medial femoral condyle region. CONCLUSIONS: Our findings demonstrate the ability to successfully transfer an osteochondral autograft plug with maintenance of chondrocyte cellular viability. The transferred cartilage is stiffer than the control medial femoral condyle cartilage, and there is concern regarding the increased trabecular mass in the healing subchondral plate, but these do not result in increased degenerative changes of the opposing articular surfaces in the short term.

Animals↗

PubMed2001

The effect of variations in applied rehabilitation force on collagen concentration and maturation at the intrasynovial flexor tendon repair site.

The biochemical means by which accelerated rehabilitation alters intrasynovial flexor tendon repair site collagen synthesis and extracellular matrix maturation are not fully understood. We hypothesized that an increased level of applied rehabilitative force in a clinically relevant animal model would hasten the maturation of the repair site extracellular matrix as demonstrated by total collagen and collagen cross-link assessment. Twenty-eight flexor digitorum profundus tendons from 14 adult dogs were transected and repaired. The animals received either low- or high-force rehabilitation and were killed 10, 21, and 42 days after surgery. A 10-mm segment of tendon surrounding the repair site was obtained. Biochemical analysis showed that total collagen concentration was significantly reduced at each time point, that the reducible cross-link ratio of dihydroxylysinonorleucine to hydroxylysinonorleucine was significantly increased at each time point, and that the nonreducible pyridinoline cross-link content was significantly decreased at 10 days in both rehabilitative groups. Total collagen content did not vary to a statistically significant degree with either time or as a function of rehabilitation type. Based on these findings several clinically relevant observations can be made. Increasing collagen concentration and repair site maturation do not explain the previously demonstrated increased tensile properties of tendon that occur between 3 and 6 weeks after repair. Higher force rehabilitation does not alter the biochemical composition of the healing tendon through 6 weeks. Coupled with other recent data these findings suggest that high-force rehabilitation does not stimulate accelerated healing after intrasynovial flexor tendon repair.

Animals↗

PubMed2001

High-efficiency non-viral transfection of primary chondrocytes and perichondrial cells for ex-vivo gene therapy to repair articular cartilage defects.

BACKGROUND: Primary perichondrial cells and chondrocytes have been used to repair articular cartilage defects in tissue engineering studies involving various animal models. Transfection of these cells with a gene that induces chondrocytic phenotype may form an ideal method to affect tissue engineering of articular cartilage. DESIGN: A protocol for high-efficiency transfection of primary perichondrial and cartilage cells was optimized. Plasmids carrying the marker beta-galactosidase (beta-gal), PTHrP and TGF-beta1 genes driven by a strong mammalian promoter were transfected into primary perichondrial cells and chondrocytes. A three-step method was used to achieve high efficiency of transfection: (1) permeabilization of primary cells using a mild detergent, (2) association of plasmid DNAs with a polycationic (poly-l-lysine) core covalently linked to a receptor ligand (transferrin), (3) introduction of cationic liposomes to form the quaternary complex. For in-vivo assessment, polylactic acid (PLA) scaffolds seeded with beta-gal transfected perichondrial cells were implanted into experimentally created osteochondral defects in rabbit knees for 1 week. RESULTS: The efficiency of transfection was determined to be over 70%in vitro. The transformed cells continued to express beta-gal, in vivo for the entire test period of 7 days. Furthermore, primary perichondrial cells transfected with TGF-beta1 and PTHrP over-expressed their cognate gene products. CONCLUSION: The ability to transfect autologous primary perichondrial cells and chondrocytes with high efficiency using a non-viral system may form a first step towards tissue engineering with these transformed cells to repair articular cartilage defects.

Animals↗

PubMed2001

Donor cell fate in tissue engineering for articular cartilage repair.

Articular cartilage repair is a clinical challenge because of its limited intrinsic healing potential. Considerable research has focused on tissue engineering and transplantation of viable chondrogenic cells to enhance cartilage regeneration. However, the question remains: do transplanted allogenic cells survive in the repair with time? This study assessed donor cell fate after transplantation of male New Zealand White rabbit perichondrium cell and polylactic acid constructs into osteochondral defects created in the medial femoral condyles of female New Zealand White rabbits. Repair tissue was harvested at 0, 1, 2, 3, 7, and 28 days after implantation and was evaluated for cell viability and total cell number using confocal microscopic analysis. The number of donor cells in each sample was estimated using quantitative polymerase chain reaction targeting a gender-specific gene present on the Y-chromosome, the sex-determining region Y gene, and a control deoxyribonucleic acid present in male and female cell deoxyribonucleic acid, the matrix metalloproteinase-1 gene promoter. Average cell viability was found to be 87% or more at all times. Donor cells were present in repair tissue for 28 days after implantation. However, the number of donor cells declined from approximately 1 million at Time 0 to approximately 140,000 at 28 days. This decline in donor cells was accompanied by a significant influx of host cells into the repair tissue. This study shows that the sex-determining region Y gene is a valuable marker for tracking the fate of transplanted allogenic cells in tissue engineering.

Animals↗

PubMed2001

Matrices for cartilage repair.

Techniques for repairing focal articular cartilage defects are evolving from methods that induce a local stimulation of fibrocartilaginous repair to methods that will lead to a hyaline articular cartilage repair. Mosaicplasty and autologous chondrocyte implantation are examples of the latter. A tissue engineered hyaline cartilage implant that could be used off the self would minimize the morbidity of these techniques. However, there are significant questions that still need to be resolved before such tissue-engineered implants will be practical. Principally among these is the question of what is the ideal matrix for such an implant, particularly from the standpoint of the best material and architecture. Second, what is the ideal cell source to use with these implants. A third major unknown is what is the most ideal way to use growth factors to enhance the repair. As these issues are resolved, the prospects of a tissue engineered cartilage replacement will advance from theory to practice.

Biocompatible Materials↗

PubMed2000

Microstructural properties of the distal growth plate of the rabbit radius and ulna: biomechanical, biochemical, and morphological studies.

The purposes of this study were to define the tensile properties of each zone of the rabbit growth plate and to correlate them with the microarchitecture and biochemical composition of the zones. The epiphysis-growth plate-metaphysis complex was obtained from the radius and ulna of 20 8-week-old rabbits. Four dye markers were placed on the growth plate. The complex was loaded to failure with a tensile testing machine, and the strain behavior was recorded simultaneously with a microscope, a charge-coupled device camera, and a video dimension-analyzer system. The collagenous fiber architecture of each zone was examined with a microscope, and the collagen content of each zone was also determined. The tangent modulus of the resting zone was 75% stiffer than that of the other two zones. The highest values for strain at failure and energy absorbed to failure were observed in the hypertrophic zone, and the total collagen content was highest in the proliferating zone. The collagen fibers were more randomly aligned in the resting zone than in the other two zones. The diversity observed in the microarchitecture of the rabbit growth plate correlates with the zone-dependent differences in its mechanical properties.

Animals↗

PubMed2000

Cartilage repair with autogenic perichondrium cell/polylactic acid grafts: a two-year study in rabbits.

The repair of articular cartilage injuries remains a challenge. In this 2-year study, osteochondral defects in the femoral condyles of five rabbits were repaired with an autogenic perichondrium cell/polylactic acid graft and compared with a contralateral control in which the defect remained empty. The rabbits in the group with the grafts had a higher percentage of biologically acceptable repairs (100%) than did those in the control group (80%). According to the histologic and histomorphometric analyses, the grafts augmented the intrinsic healing. Nonetheless, the results for the grafts were tarnished by a depressed repair surface and a histologic appearance not equivalent to that of normal cartilage. The application of growth factors to this model may yield a clinical treatment.

Animals↗

PubMed2000

The effects of hyaluronan on the meniscus in the anterior cruciate ligament-deficient knee.

Anterior cruciate ligament (ACL) deficiency often induces meniscal tears and, ultimately, degenerative joint disease. The hypothesis of this study was that hyaluronan (HA; MW = 8 x 105) may have a protective effect on the medial meniscus following a period of ACL deficiency. The animal model consisted of creating an ACL deficiency by ACL transection (ACLT) in 51 mature New Zealand white rabbits. Postoperative injections started 4 weeks after ACLT to allow the ACL deficiency to create a degenerative change in the meniscus. The first group (n = 26) was injected with HA and the second group (n = 25) was injected with vehicle (phosphate-buffered saline) in their ACL-deficient knees once a week for 5 weeks, in a protocol similar to that used clinically. At the end of the injections, the HA-treated menisci showed a reduced meniscus area histomorphometrically (P<0.01), as well as a decrease in water content (P<0.01) when compared with the vehicle-treated menisci. The matrix composition of the menisci was assessed by the total glycosaminoglycans (GAGs) content, which decreased in the vehicle-treated menisci (P<0.05) but did not decrease in the HA-treated menisci. In our model, a positive effect of HA was observed biochemically on the preservation of the meniscus matrix composition in the ACL-deficient knee.

Animals↗

PubMed2000

The long-term effects of hyaluronan during development of osteoarthritis following partial meniscectomy in a rabbit model.

OBJECTIVE: The long-term effect of hyaluronan (HA) on meniscus remodeling and articular cartilage preservation was assessed during the development of osteoarthritis following partial meniscectomy in a rabbit model. DESIGN: Approximately 60% of the region of each medial meniscus of 20 rabbit knees was excised bilaterally. The left knee joint was treated with five weekly intraarticular injections of 0.3 ml of HA, beginning 1 week after surgery. The right control knee was injected with PBS on the same schedule. Six months after surgery, animals were killed and the medial menisci and tibial articular cartilage were evaluated morphologically, histologically and biochemically. RESULTS: Meniscal regeneration was observed as newly synthesized translucent tissue, and image analysis revealed that the amount of this tissue was significantly greater in the HA-treated menisci than in the vehicle-treated menisci. Safranin-O staining and image analysis revealed the increased presence of glycosaminoglycans in the HA-treated menisci relative to vehicle-treated menisci while vascularity and biochemical parameters (hydration, total GAGs and reducible collagen crosslinks) were statistically similar in HA- and vehicle-treated menisci. Gross morphologic grading with India ink revealed a trend for less deterioration of tibial articular cartilage in the HA group (P=0.09) while Mankin's score of the HA-treated tibial articular cartilage was marginally lower than that of the vehicle group (P=0.06). Biochemical assessments showed a trend for higher total GAGs concentration in the HA-treated articular cartilage when compared to the vehicle treatment group (P=0.06). CONCLUSION: The present study has demonstrated that following partial meniscectomy, treatment with hyaluronan can enhance meniscal regeneration and may inhibit articular cartilage degeneration as long as six months post surgery.

Animals↗

PubMed2000

Novel method for the quantitative assessment of cell migration: a study on the motility of rabbit anterior cruciate (ACL) and medial collateral ligament (MCL) cells.

A novel method of quantitating cell migration has been proposed for the potential utilization of tissue engineered scaffolds. Applying Alt's conservation law to describe the motion of first passage ACL and MCL cells, we have developed a quantitative method to assess innate differences in the motility of cells from these two ligamentous tissues. In this study, first passage ACL and MCL cells were cultured from four mature New Zealand white rabbits. One side of the cell monolayer was scraped completely away to create a wound model. The cell moved into the cell-free area, and cell density profiles were analyzed at 6 h and 12 h. Values of the random motility coefficient (mu) were then estimated by curve fitting the 6 h and 12 h data to a mathematical model, derived from the conservation law of cell flux. During 6 h of incubation in medium supplemented with 1% FBS, MCL cells (mu(MCL) = 4.63 +/- 0.65 X 10(-6) mm(2)/sec) were significantly (p < 0.05) more mobile than ACL cells (mu(ACL) = 2.51 +/- 0.31 X 10(-6) mm(2)/sec). At 12 h, the MCL cells also appeared to move faster (mu(ACL) = 4.39 +/- 0.63 X 10(-6) mm(2)/sec, mu(MCL) = 6.59 +/- 1.47 X 10(-6) mm(2)/sec), but the difference was not statistically significant (p = 0.18). Exposure of the cells to growth factors PDGF-BB or bFGF for 6 h had no significant effect on the migration of the ACL and MCL cells. However, exposure of the ACL cells (p < 0.05) and the MCL cells (p = 0.19) to 1 ng/mL of PDGFBB for 12 h enhanced their migration. Incubation with a high concentration (100 ng/mL) of PDGF-BB or bFGF at concentrations tested (1 or 100 ng/mL) for 12 h, produced little or no migratory stimulation on these ligament cells. Our findings support the previous qualitative observations made by numerous investigators. The novel methodology developed in this study may provide a basis for tissue engineering, and the results may be applied to tissue reconstruction techniques of the knee ligaments.

Animals↗

PubMed2000

Cartilage repair with autogenic perichondrium cell and polylactic acid grafts.

The repair of articular cartilage injuries remains a challenge, with many of the current therapeutic strategies based on the grafting or recruitment of chondrogenic tissues or cells. This 1-year study compared the repair of a 3.7-mm diameter by 3-mm deep osteochondral defect in the medial femoral condyle of 24 New Zealand White rabbits; the defect was obtained using an autogenic perichondrium cell polylactic acid composite graft with a contralateral control in which the osteochondral defect remained empty. To elucidate the effect of host immune responses on the repair process after perichondrium cell transplantation, the results of the autogenic perichondrium cell polylactic acid graft group were compared with those obtained in the authors' previous 1-year study of allogenic perichondrium cell polylactic acid composite grafts implanted in a similar model. One year after surgery, the repair site underwent gross inspection and histologic, histomorphometric, biochemical, and biomechanical analyses. The autogenic perichondrium cell polylactic acid graft group (92%) and the control group in which the osteochondral defect remained empty (88%) resulted in a high percentage of grossly acceptable repairs. The autogenic grafts appeared to augment the intrinsic healing capacity of the animals (as compared with the animals in the No Implant Group). The autogenic perichondrium cell polylactic and grafts improved the histologic appearance and percentage of Type II collagen of the cartilaginous repair tissue. Compared with allogenic grafts, the autogenic grafts had better reconstitution of the subchondral bone. However, the results of this experimental model suggest a suboptimal concentration of glycosaminoglycans in the neocartilage matrix, a depressed surface of the repair tissue, a histologic appearance that was not equivalent to that of normal articular cartilage, and reduced biomechanical properties for the repair tissue. The future application of growth factors to this model may yield a treatment that can be applied in the clinical arena.

Animals↗

PubMed2000

Nonviral in vivo gene therapy for tissue engineering of articular cartilage and tendon repair.

Heretofore, nonviral methods have been used primarily for in vitro transfection of cultured cell lines. These methods were substantially less efficient when compared with the use of viruses, particularly when used in vivo. Herein a three-step, highly efficient method of nonviral gene delivery is presented. Using this method, genes have been delivered successfully into tissues of orthopaedic importance with high-efficiency by nonviral means. Transforming growth factor-beta 1, parathyroid hormone related protein, and a marker gene were transfected into primary perichondrium and cartilage cells with efficiencies in excess of 70%. They overexpressed their cognate gene products showing efficacy of expression in a rabbit model of osteochondral defect repair. Using the same method, a marker gene was delivered into a canine model for intrasynovial flexor tendon injury and repair. This was achieved by direct gene delivery during surgery. An estimated 5 additional minutes were required during surgery to complete the transfection steps. High efficiency gene delivery was achieved in the flexor tendons, tendon sheaths, tendon pulleys, surrounding tissues, and skin. The efficiency of transfection approached 100% in the exposed superficial tissue layers and transfected cells were found several layers below the exposed tissue surfaces. The data show the potential of direct nonviral gene therapy in orthopaedics for ex vivo and in vivo applications.

Animals↗

PubMed2000

The tetrabasic KKKK(147-150) motif determines intracrine regulatory effects of PthrP 1-173 on chondrocyte PPi metabolism and matrix synthesis.

Expression of PTHrP is a major regulator of growth cartilage development and also becomes robust in osteoarthritic cartilage. We further defined how PTHrP 1-173, which we observed to be the preferentially expressed PTHrP isoform in normal and osteoarthritic cartilage, functions in chondrocytes. We transfected both immortalized human juvenile costal chondrocytes (TC28 cells) and rabbit articular chondrocytes with wild-type PTHrP 1-173 and mutants of putative PTHrP 1-173 endoproteolytic processing sites. Wild-type PTHrP 1-173 inhibited collagen synthesis and decreased extracellular PPi (which critically regulates hydroxyapatite deposition) by 50-80% in both chondrocytic cell types. In contrast, PTHrP 1-173 mutated at the PTHrP 147-150 motif KKKK (but not the other site-directed mutants) and increased both extracellular PPi and collagen synthesis by >50%. Synthetic PTHrP 140-173 mutated at amino acids 147-150 and also increased extracellular PPi, and wild-type 140-173 decreased extracellular PPi in permeabilized cells. The 147-nuclear localization of PTHrP. We conclude that the tetrabasic 147-150 motif functions to determine how PTHrP 1-173 regulates collagen synthesis and levels of extracellular PPi by an intracrine mechanism in chondrocytes, and it may prove useful as a therapeutic target for regulation of mineralization.

Animals↗

PubMed2000

Effect of hyaluronan on chondrocyte apoptosis and nitric oxide production in experimentally induced osteoarthritis.

OBJECTIVE: Nitric oxide (NO) plays an important role in cartilage degeneration, and NO donors induce chondrocyte apoptosis. This study evaluated the effect of intraarticular injections of hyaluronan (HA) on chondrocyte apoptosis and NO production using an experimental osteoarthritis (OA) model. METHODS: Thirty-six New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT), and were divided into 3 groups. Four weeks after ACLT, the HA group started intraarticular HA injections once a week for 5 weeks; the vehicle group started to receive the carrier of HA; the no injection group received no treatment. All ACLT knees were harvested at Week 9 and evaluated for OA severity. Culture supernatants of the cartilage were analyzed for nitrite concentration. Cartilage sections were analyzed by TUNEL for apoptosis and by immunohistochemistry for nitrotyrosine. RESULTS: OA in the HA group was less severe than the other 2 groups. The number of apoptotic chondrocytes was significantly lower in the HA group. HA injection did not influence NO production in cartilage. CONCLUSION: HA protects against chondrocyte apoptosis during the development of OA, while it may not have definite effects on NO production in the joints. These inhibitory effects of HA on chondrocyte apoptosis may play a role in its mechanism of action in chondroprotection.

Animals↗