Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels of six lysosomal enzymes (acid phosphatase, beta-acetylglucosaminidase, cathepsin D, beta-galactosidase, arylsulfatase A, and beta-glucuronidase) and four neutral and alkaline hydrolases (esterase, inorganic phyrophosphatase, alkaline phosphatase, and 5'-nucleotidase) were measured in osteoarthritic, rheumatoid and control synovia. All enzyme levels in diseased synovium except esterase values in osteoarthritis were significantly elevated compared with controls. The mean values of the group of acid hydrolases and the group of neutral and alkaline hydrolases in osteoarthritic synovia were 1.9- and 2.0-fold greater than those of control specimens. In rheumatoid synovia, the values were 4.2- and 4.5 fold greater than control for the same enzymes. Levels in rheumatoid synovia were significantly higher than those in osteoarthritic synovia with the exception of 5'-nucleotidase. Only a limited correlation between the extents of inflammation present in the synovia and the levels of a lysosomal marker enzyme (cathepsin D) was observed. These results demonstrate that whatever the mechanism, increased levels of acid hydrolases as well as certain neutral and alkaline hydrolases are present in osteoarthritic and rheumatoid synovia, and these enzymes are probably contained in the synovial lining cells.
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PMID:Acid, neutral, and alkaline hydrolases in arthritic synovium. 0 9

Gene therapy used in the context of delivering a therapeutic gene(s) to chondrocytes offers a new approach for treating chondrocyte-mediated cartilage degradation associated with various human arthropathies including osteoarthritis. In this study, gene delivery to human osteoarthritis chondrocytes in monolayer culture was demonstrated using two adenoviral vectors (Ad.CMVlacZ and Ad.RSVntlacZ) carrying the Escherichia coli beta-galactosidase marker gene, and a third vector (Ad.RSV hIL-1ra) containing the cDNA for human interleukin-1 receptor antagonist. At an moi of 10(3) plaque-forming units/chondrocyte, > 90% of the infected cells stained positive for E. coli beta-galactosidase activity, indicating a high efficiency of transduction. Genetically modified chondrocytes were then transplanted onto the articular surface of osteoarthritic cartilage organ cultures with and without the underlying subchondral bone. Both in situ staining of the cartilage organ cultures for E. coli beta-galactosidase activity and examination by scanning electron microscopy indicated that the transplanted chondrocytes adhered and integrated into the articular surface and continued to express transgenic protein. Chondrocytes transduced with Ad.RSV hIL-1ra and seeded onto the surface of osteoarthritic cartilage secreted high levels of biologically active IL-1 receptor antagonist. The Ad.RSV hIL-1ra-treated cartilage samples were resistant to IL1-induced proteoglycan degradation over 10 d of sustained organ culture. These data demonstrate that transplantation of transduced chondrocytes onto the articular surface protects cartilage from IL-1-induced extracellular matrix degradation.
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PMID:Transplantation of transduced chondrocytes protects articular cartilage from interleukin 1-induced extracellular matrix degradation. 759 34

Gene transfer to chondrocytes followed by intra-articular transplantation may allow for functional modulation of chondrocyte biology and enhanced repair of damaged articular cartilage. We chose to examine the loss of chondrocytes transduced with a recombinant adenovirus containing the gene for Escherichia coli beta-galactosidase (Ad.RSVntlacZ), followed by transplantation into deep and shallow articular cartilage defects using New Zealand White rabbits as an animal model. A type I collagen matrix was used as a carrier for the growth of the transduced chondrocytes and to retain the cells within the surgically created articular defects. Histochemical analysis of matrices recovered from the animals 1, 3 and 10 days after implantation showed the continued loss of lacZ positive chondrocytes. The number of cells recovered from the matrices was also compared with the initial innoculum of transduced cells present within the matrices at the time of implantation. The greatest loss of transduced cells was observed in the first 24 h after implantation. The numbers of transduced cells present within the matrices were relatively constant between 1 and 3 days postimplantation, but had progressively declined by 10 days postimplantation. These results suggest that transduction of chondrocytes followed by intra-articular transplantation in this rabbit model may enable us to examine the biological effects of focal transgenic overexpression of proteins involved in cartilage homeostasis and repair.
Osteoarthritis Cartilage 1997 Jul
PMID:Transplantation of adenovirally transduced allogeneic chondrocytes into articular cartilage defects in vivo. 940 72

Aging and the degeneration of articular cartilage in osteoarthritis are distinct processes, but a strong association exists between age and the incidence and prevalence of osteoarthritis. We hypothesized that this association is due to in vivo replicative senescence, which causes age-related declines in the ability of chondrocytes to maintain articular cartilage. For this hypothesis to be tested, senescence-associated markers were measured in human articular chondrocytes from donors ranging in age from 1 to 87 years. These measures included in situ staining for senescence-associated beta-galactosidase activity, (3)H-thymidine incorporation assays for mitotic activity, and Southern blots for telomere length determinations. We found that senescence-associated beta-galactosidase activity increased with age, whereas both mitotic activity and mean telomere length declined. These findings indicate that chondrocyte replicative senescence occurs in vivo and support the hypothesis that the association between osteoarthritis and aging is due in part to replicative senescence. The data also imply that transplantation procedures performed to restore damaged articular surfaces could be limited by the inability of older chondrocytes to form new cartilage after transplantation.
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PMID:Telomere erosion and senescence in human articular cartilage chondrocytes. 1128 88

Osteoarthritis (OA), the disease characterized by joint pain and loss of joint form and function due to articular cartilage degeneration, is not an inevitable consequence of aging, but a strong association exists between age and increasing evidence of OA. Aging changes in articular cartilage that increase the risk of articular cartilage degeneration include fibrillation of the articular surface, decrease in the size and aggregation of proteoglycan aggrecans, increased collagen cross-linking and loss of tensile strength and stiffness. These alterations are most likely primarily the result of aging changes in chondrocyte function that decrease the ability of the cells to maintain the tissue including decreased synthetic activity, synthesis of smaller less uniform aggrecans and less functional link proteins and decreased responsiveness to anabolic growth factors. Our recent work suggests that the cause of the age-related loss of chondrocyte function may be progressive senescence of articular cartilage chondrocytes marked by a decline in mitotic activity, increased expression of the senescence-associated enzyme beta-galactosidase and erosion of telomere length. New efforts to prevent the development or progression of OA might include strategies that delay the onset of chondrocyte senescence or replace senescent cells.
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PMID:Roles of articular cartilage aging and chondrocyte senescence in the pathogenesis of osteoarthritis. 1181 39

Although osteoarthritis (OA) is not an inevitable consequence of aging, a strong association exists between age and increasing incidence of OA. We hypothesized that this association is due to in vivo articular cartilage chondrocyte senescence which causes an age-related decline in the ability of the cells to maintain articular cartilage, that is, increasing age increases the risk of OA because chondrocytes lose their ability to replace their extracellular matrix. To test this hypothesis, we measured senescence markers in human articular cartilage chondrocytes from 27 donors ranging in age from one to 87 years. The markers included expression of the senescence-associated enzyme beta-galactosidase, mitotic activity measured by 3H-thymidine incorporation, and telomere length. beta-galactosidase expression increased with age (r=0.84, p=0.0001) while mitotic activity and mean telomere length declined (r=-0.774, p=0.001 and r=-0.71, p=0.0004, respectively). Decreasing telomere length was strongly correlated with increasing expression of beta-galactosidase and decreasing mitotic activity. These findings help explain the previously reported age related declines in chondrocyte synthetic activity and responsiveness to anabolic growth factors and indicate that in vivo articular cartilage chondrocyte senescence is responsible, at least in part, for the age related increased incidence of OA. The data also imply that people vary in their risk of developing OA because of differences in onset of chondrocyte senescence; and, the success of chondrocyte transplantation procedures performed to restore damaged articular surfaces in older patients could be limited by the inability of older chondrocytes to form new cartilage. New efforts to prevent the development or progression of OA might include strategies that delay the onset of chondrocyte senescence or replace senescent cells.
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PMID:Human chondrocyte senescence and osteoarthritis. 1208 77

The incidence of osteoarthritis (OA), the disease characterized by joint pain and loss of joint form and function due to articular cartilage degeneration, is directly correlated with age. The strong association between age and increasing incidence of osteoarthritis (OA) marks OA as an age related disease. Yet, like many other age related diseases, OA is not an inevitable consequence of aging; instead, aging increases the risk of OA. Articular cartilage aging changes that may lead to articular cartilage degeneration include fraying and softening of the articular surface, decreased size and aggregation of proteoglycan aggrecans and loss of matrix tensile strength and stiffness. These changes most likely are the result of an age related decrease in the ability of chondrocytes to maintain and repair the tissue manifested by decreased mitotic and synthetic activity, decreased responsiveness to anabolic growth factors and synthesis of smaller less uniform aggrecans and less functional link proteins. Our recent work suggests that progressive chondrocyte senescence marked by expression of the senescence associated enzyme beta-galactosidase, erosion of chondrocyte telomere length and mitochondrial degeneration due to oxidative damage causes the age related loss of chondrocyte function. New efforts to prevent the development and progression of OA might include strategies that slow the progression of chondrocyte senescence or replace senescent cells.
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PMID:Aging, articular cartilage chondrocyte senescence and osteoarthritis. 1223 62

Replicative senescence occurs when normal somatic cells stop dividing. Senescent cells remain viable, but show alterations in phenotype, e.g. altered expression of matrix metalloproteinases (MMPs); these enzymes are known to be involved in cartilage destruction. It is assumed that cells deplete their replicative potential during aging, and age is a major risk factor for osteoarthritis (OA). Therefore, we hypothesized that chondrocytes in aging or diseased cartilage become senescent with associated phenotypic changes contributing to development or progression of OA. Articular cartilage was obtained from OA patients undergoing arthroplasty, with 'normal' cartilage from trauma surgery for hip fracture. Senescent cells were identified using the senescence-associated beta-galactosidase (SA-beta-gal) marker. Telomere length was assessed using Southern blot. MMP expression was measured at the mRNA level using Taqman RT-PCR. No SA-beta-gal staining was observed in control cartilage regardless of patient age. In contrast, SA-beta-gal staining was observed in damaged OA cartilage adjacent to the lesion. Cultured chondrocytes isolated from sites near a lesion contained a greater percentage of SA-beta-gal positive cells than cultures isolated from distal sites or normal cartilage. Mean telomere length was shorter in cells near the lesion compared to distal sites in the same joint; thus the former population has undergone cell division. The expression of collagenases MMP-1, -8 and -13 and tissue inhibitor of metalloproteinases (TIMP)-1 was altered in OA cartilage, but no difference was detected between lesion and distal sites in the same joint (i.e. no correlation was found between senescent cells and proteinase/ inhibitor expression).
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PMID:The role of chondrocyte senescence in osteoarthritis. 1288 54

Joint injuries frequently lead to progressive joint degeneration that causes the clinical syndrome of post-traumatic osteoarthritis. The pathogenesis of osteoarthritis remains poorly understood, but patient age is a significant risk factor for progressive joint degeneration. We have found that articular cartilage chondrocytes show strong evidence of senescence with increasing age, including synthesis of smaller more irregular aggrecans; increased expression of lysosomal beta-galactosidase and telomere erosion; and decreased proteoglycan synthesis, response to the anabolic cytokine IGF-I, proliferative capacity, and mitochondrial function. These observations help explain the strong association between age and joint degeneration, but they do not explain how joint injury increases the risk of joint degeneration in younger individuals. We hypothesized that excessive loading of articular surfaces due to acute joint trauma or post-traumatic joint instability, incongruity or mal-alignment increases release of reactive oxygen species, and that the increased oxidative stress on chondrocytes accelerates chondrocyte senescence thereby decreasing the ability of the cells to maintain or restore the tissue. To test this hypothesis, we exposed human articular cartilage chondrocytes from young adults to mechanical and oxidative stress. We found that shear stress applied to cartilage explants in a triaxial pressure vessel increased release of reactive oxygen species and oxidative stress induced chondrocyte senescence (as measured by expression of lysosomal beta-galactosidase, nuclear and mitochondrial DNA damage and decreased mitochondrial function). These observations support the hypothesis that joint injury accelerates chondrocyte senescence and that this acceleration plays a role in the joint degeneration responsible for post-traumatic osteoarthritis.
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PMID:Post-traumatic osteoarthritis: the role of accelerated chondrocyte senescence. 1529 79

cellular level is not completely understood, but both aging and loading-induced stresses have been shown to undermine cell functions related to the maintenance and restoration of the cartilage matrix. Based on precedents set by studies of other age-related degenerative diseases, we have focused our laboratory work on senescence as the cause of age-dependent decline in chondrocytes and on the impact of excessive mechanical stresses in promoting senescence. We hypothesized that senescent chondrocytes accumulate with age in articular cartilage and we propose that excessive mechanical stress plays a role in this process by promoting oxidative damage in chondrocytes that ultimately causes them to senesce. To test this hypothesis, we measured cell senescence markers (beta-galactosidase expression, mitotic activity, and telomere length) in human articular cartilage chondrocytes, and determined the effects of chronic exposure to oxidative stress on chondrocyte growth and senescence. In addition, we measured the effects of abnormally high levels of mechanical shear stress on the release of oxidants in cartilage explants. We found that senescent chondrocytes accumulated with age in articular cartilage. In vitro studies showed that chronic oxidative stress caused by repeated exposure to peroxide, or by growth under superphysiologic oxygen tension caused chondrocyte populations to senesce prematurely, before extensive telomere erosion occurred. Mechanical shear stress applied to cartilage explants considerably increased the production of oxidants. These observations support the hypothesis that senescence accounts for age-related decline in chondrocyte function and indicate that mechanically induced oxidative damage plays a role in this process. This suggests that new efforts to prevent the development and progression of osteoarthritis should include strategies that slow the progression of chondrocyte senescence or replace senescent cells.
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PMID:Chondrocyte senescence, joint loading and osteoarthritis. 1548 82


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