Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fibrous interface tissue between hip prostheses and surrounding bone is often morphologically and functionally synovial-like. The fibroblast is the major cell type; but also giant cells and macrophages are present, and their numbers are increased in the occasional adverse-type host reaction to the prosthesis. Adverse lytic reactions are often associated with methylmethacrylate debris, whereas in cementless cases, polyethylene and metallic (titanium) wear debris seem to cause adverse reactions. Osteoblasts, osteoclasts, and mesenchymal collagenase secreted by fibroblasts and macrophages play an important role in the process of prosthetic loosening. Methylmethacrylate is immunologically relatively inert, while it induces inflammatory mononuclear-cell migration. Both cemented and cementless prostheses cause a foreign-body type host response, including adaptive and reactive processes. This response includes the formation of fibroblast-like B-type lining cells, which are able to synthesize and secrete hyaluronate. Material surfaces of hip arthroplasty components also provide a unique environmental niche to which staphylococcal strains adhere and colonize. Antibiotic resistance is related to the material colonized rather than to the presence of an exopolysaccharide barrier; organisms bound to polyethylene and methylmethacrylate are more resistant than organisms that are bound to stainless steel. An understanding of prosthetic biocompatibility requires an appreciation of tissue cell, bacterial cell and host defense-system response to biomaterials. The site of implantation is a stage on which the "players" (bacteria, host cells, and organic moieties) interact and compete, and before which the host is a "responsive audience."
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PMID:Cemented versus cementless hip arthroplasty. A review of prosthetic biocompatibility. 159 66

Large amounts of metal and polyethylene debris and high ion readings are found in capsule and fibrous membranes of both loose titanium and cobalt-chromium stems. Prostaglandin E2, interleukin-1, and collagenase levels are elevated when compared to control values with collagenase having the highest and most consistent elevations. Synovial fluid and blood ion readings were elevated in loose cemented and cementless stems made from both materials. Blood ion readings were not elevated in fixed stems. Fixed stems had much less particulate debris in soft tissues. The data showed that failure of most metal hip stems was initially due to a mechanical cause, with high debris and ion counts occurring secondarily in capsule and fibrous membranes. Particulate debris and high ion readings are primarily a focal problem contained by the periprosthetic fibrous connective-tissue encapsulation within the femoral canal and joint capsules. No systemic problems were manifest in any of the patients examined and followed in this study.
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PMID:Histologic, biochemical, and ion analysis of tissue and fluids retrieved during total hip arthroplasty. 217 87

A method for isolating and culturing osteoclast-like cells from cancellous bone material collected from external iliac crest bone of patients is described. Aseptic techniques were used for comminution of the bone material, treatment with collagenase and separation of the bone cells from the bulk bone through a nylon filter. The bone cells were cultured on various surfaces for ten days. Cell motility, mobility and fusion was be observed along with tartrate-resistant acidic phosphatase activity in a majority of the cells soon after they had been cultured. These large cells attached to human cortical bone fragments, where they produced resorption lacunae in vitro. These morphologic and functional characteristics indicate that the cells we had isolated were, in fact, human osteoclasts. SEM studies of these cells on various biomaterials (titanium, hydroxyl apatite, tricalcium phosphate) revealed different morphologic characteristics varying with the substrate used and allowing conclusions as to substrate acceptance. Large areas of cell contact and cell proliferation suggest a favorable response to the materials applied.
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PMID:[Cell cultures of human osteoclasts for testing biomaterials]. 217 62

Periprosthetic osteolysis with or without aseptic loosening is a major clinical problem in total hip arthroplasty. While the macrophage response to prosthetic wear debris and its role in periprosthetic osteolysis has been extensively studied, information regarding other cell types (fibroblasts, osteoblasts) is limited. This study explored the response of fibroblasts to particulate wear debris. Fibroblasts isolated from interfacial membranes of patients with failed total hip replacements and normal synovial tissue, when challenged with small-sized ( < 3 microns) titanium (Ti) particles, responded with significantly enhanced expressions of collagenase, stromelysin and, to a much lesser extent, their tissue inhibitor of metalloproteinases (TIMP). These "regulated" expressions at both mRNA and protein levels were correlated with the size and composition of particles. De novo protein synthesis was required for the regulation of these mRNAs. A similar effect could be induced by the treatment of the cells with particle-free conditioned medium from Ti particle-stimulated fibroblasts. Furthermore, this conditioned medium significantly suppressed the mRNA levels of procollagen alpha 1 (I) and alpha 1 (III) in osteoblast-like MG-63 cells. It is concluded that fibroblasts stimulated with certain particle debris may play an important role in periprosthetic osteolysis by releasing bone-resorbing metalloproteinases and mediator(s) which resulted in suppressed collagen synthesis in osteoblasts.
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PMID:The potential role of fibroblasts in periprosthetic osteolysis: fibroblast response to titanium particles. 750 15

The effect on chondrocyte metabolism of culture surfaces sputter-coated with various materials used for orthopaedic implants was studied and correlated with the stage of cartilage cell maturation. Confluent, fourth-passage chondrocytes from the costochondral resting zone and growth zone of rats were cultured for 6 or 9 days on 24-well plates sputter-coated with ultrathin films of titanium, titanium dioxide, aluminum oxide, zirconium oxide, and calcium phosphate (1.67:1). Corona-discharged tissue culture plastic served as the control. The effect of surface material was examined with regard to cell morphology; cell proliferation (cell number) and DNA synthesis ([3H]thymidine incorporation); RNA synthesis ([3H]uridine incorporation); collagenase-digestible protein, noncollagenase-digestible protein, and percentage of collagen production; and alkaline phosphatase-specific activity, both in the cell layer and in trypsinized chondrocytes. Cell morphology was dependent on surface material; only cells cultured on titanium had an appearance similar to that of cells cultured on plastic. While titanium or titanium dioxide surfaces had no effect on cell number or [3H]thymidine incorporation, aluminum oxide, calcium phosphate, and zirconium oxide surfaces inhibited both parameters. Cells cultured on aluminum oxide, calcium phosphate, zirconium oxide, and titanium dioxide exhibited decreased collagenase-digestible protein, noncollagenase-digestible protein, and percentage of collagen production, but [3H]uridine incorporation was decreased only in those chondrocytes cultured on aluminum oxide, calcium phosphate, or zirconium oxide. Chondrocytes cultured on titanium had greater alkaline phosphatase-specific activity than did cells cultured on plastic, but the incorporation of [3H]uridine and production of collagenase-digestible protein, noncollagenase-digestible protein, and percentage of collagen was comparable. The response of chondrocytes from the growth zone and resting zone to culture surface was comparable, differing primarily in magnitude. Cell maturation-dependent effects were evident when enzyme activity in trypsinized and scraped cells was compared. These results indicate that different surface materials affect chondrocyte metabolism and phenotypic expression in vitro and suggest that implant materials may modulate the phenotypic expression of cells in vivo.
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PMID:Culture surfaces coated with various implant materials affect chondrocyte growth and metabolism. 752 Apr 86

The effect of surface roughness on osteoblast proliferation, differentiation, and protein synthesis was examined. Human osteoblast-like cells (MG63) were cultured on titanium (Ti) disks that had been prepared by one of five different treatment regimens. All disks were pretreated with hydrofluroic acid-nitric acid and washed (PT). PT disks were also: washed, and then electropolished (EP); fine sandblasted, etched with HCl and H2SO4, and washed (FA); coarse sandblasted, etched with HCl and H2SO4, and washed (CA); or Ti plasma-sprayed (TPS). Standard tissue culture plastic was used as a control. Surface topography and profile were evaluated by brightfield and darkfield microscopy, cold field emission scanning electron microscopy, and laser confocal microscopy, while chemical composition was mapped using energy dispersion X-ray analysis and elemental distribution determined using Auger electron spectroscopy. The effect of surface roughness on the cells was evaluated by measuring cell number, [3H]thymidine incorporation into DNA, alkaline phosphatase specific activity, [3H]uridine incorporation into RNA, [3H]proline incorporation into collagenase digestible protein (CDP) and noncollagenase-digestible protein (NCP), and [35S]sulfate incorporation into proteoglycan. Based on surface analysis, the five different Ti surfaces were ranked in order of smoothest to roughest: EP, PT, FA, CA, and TPS. A TiO2 layer was found on all surfaces that ranged in thickness from 100 A in the smoothest group to 300 A in the roughest. When compared to confluent cultures of cells on plastic, the number of cells was reduced on the TPS surfaces and increased on the EP surfaces, while the number of cells on the other surfaces was equivalent to plastic. [3H]Thymidine incorporation was inversely related to surface roughness. Alkaline phosphatase specific activity in isolated cells was found to decrease with increasing surface roughness, except for those cells cultured on CA. In contrast, enzyme activity in the cell layer was only decreased in cultures grown on FA- and TPS-treated surfaces. A direct correlation between surface roughness and RNA and CDP production was found. Surface roughness had no apparent effect on NCP production. Proteoglycan synthesis by the cells was inhibited on all the surfaces studied, with the largest inhibition observed in the CA and EP groups. These results demonstrate that surface roughness alters osteoblast proliferation, differentiation, and matrix production in vitro. The results also suggest that implant surface roughness may play a role in determining phenotypic expression of cells in vivo.
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PMID:Effect of titanium surface roughness on proliferation, differentiation, and protein synthesis of human osteoblast-like cells (MG63). 754 45

An in vivo canine model was developed to investigate the histologic and biochemical parameters associated with aseptic loosening. Thirty-eight canines had cementless total hip arthroplasty. Experimental groups were designed specifically to investigate the relative contributions of implant motion and particulate debris (cobalt chrome alloy, titanium aluminum vanadium, and polyethylene) on the resultant periprosthetic tissues. Tissues from a stable, well-ingrown prosthesis provided a control. Importantly, the histologic and biochemical characteristics of the experimentally induced membranes consistently correlated with previous in vitro reports of tissues retrieved at revision surgery for aseptic loosening. Implant motion and all 3 particulate debris groups resulted in increased numbers of macrophages in the periprosthetic membranes. The histologic findings paralleled the increase in levels of biochemical mediators of bone resorption as measured by collagenase, gelatinase, prostaglandin E2, and interleukin-1 activity. The most striking results were seen in the histology and biochemistry of the particle groups with highly cellular membranes showing increased biochemical activity when compared with controls. The clinical relevance of this work lies in the description of an in vivo model of aseptic loosening that can be used to investigate the effects of numerous variables implicated in aseptic loosening. Ultimately, the model may serve as a basis for developing therapeutic interventions.
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PMID:Aseptic loosening in uncemented total hip arthroplasty in a canine model. 755 20

Biochemical, histological, and immunohistochemical studies of interface membranes surrounding failed hip prostheses that had been inserted without cement were done to examine specific factors involved in the development of aseptic loosening. Membranes from sixty-four femoral components were obtained from sixty-three patients during revision arthroplasty. Fifty-seven membranes were from implants that articulated with polyethylene (thirty-two were made of cobalt-chromium alloy and twenty-five, titanium alloy), and seven were from unipolar endoprostheses made of cobalt-chromium alloy that did not articulate with polyethylene. The membranes from implants with a polyethylene articulation produced significantly higher levels of collagenase and interleukin-1 (p < 0.05). However, there was no significant difference in the levels of prostaglandin E2 between the three groups. Furthermore, membranes from implants with roentgenographic evidence of focal osteolysis (endosteal erosion) released significantly higher levels of interleukin-1 (p < 0.05) than did membranes from implants without focal osteolysis. Although the membranes from the titanium-alloy implants tended to contain more metal debris than those from the cobalt-chromium-alloy implants, the biochemical findings were not significantly different between these two groups. Many macrophages that were filled with polyethylene and metal debris were present in the membranes from both groups with a polyethylene articulation. Few T lymphocytes or B lymphocytes were identified in the three groups.
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PMID:In vivo and in vitro analysis of membranes from hip prostheses inserted without cement. 811 50

Osteolysis is a central feature of aseptic loosening of orthopaedic joint prostheses. This destructive process is believed to result from phagocytosis of implant wear debris by periprosthetic and synovial macrophages and the subsequent release of proinflammatory mediators, including collagenase. Isolated murine macrophages were cultured in vitro with particulate titanium in order to explore the mechanism of macrophage activation by particulate wear debris. The results, in which the amount of secreted, soluble collagenase in culture supernatants was inversely proportional to titanium concentration, suggested that titanium strongly adsorbed secreted collagenase. This inference was confirmed by direct binding assays in which particulate titanium coated with adsorbed collagenase bound an alkaline phosphatase conjugated anti-collagenase antibody, but not a conjugated anti-IgG antibody. Adsorption of collagenase was not influenced by preincubation of titanium particles with albumin. The adsorbed collagenase remained enzymatically active as indicated by its ability to hydrolyze a synthetic peptide substrate. These results demonstrate that particulate titanium stimulates collagenase production by macrophages and then strongly adsorbs the secreted proinflammatory enzyme. The process of macrophage stimulation, collagenase secretion, and adsorption may represent an important mechanism for localization and concentration of collagenase in periprosthetic and synovial tissue, a mechanism that ultimately triggers bone resorption through osteoclast activation.
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PMID:Adsorption of collagenase to particulate titanium: a possible mechanism for collagenase localization in periprosthetic tissue. 858 May 43

Titanium-aluminum-vanadium wear particles isolated from the soft-issue membrane of a failed total hip arthroplasty were added to human fibroblasts in cell culture. The cellular response to particle challenge was determined by assaying for levels of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, prostaglandin E2, basic fibroblast growth factor, platelet-derived growth factor-AB, and transforming growth factor-beta. Collagenase and gelatinase activities were analyzed by zymography and [3H]collagen degradation. Cell viability was assessed by measuring the uptake of [3H]thymidine. Over the range of particle concentrations tested, cell viability, as demonstrated by [3H]thymidine uptake, remained unaffected. Fibroblasts exhibited a dose-dependent release of interleukin-6 in response to exposure to titanium-aluminum-vanadium particles. At 6 and 48 hours, the highest concentration of titanium alloy particles (0.189% [vol/vol]) resulted in 7-fold and 16-fold increases in interleukin-6 release, respectively, when compared with negative controls. Neither interleukin-1 beta nor tumor necrosis factor-alpha was detected in the culture medium at any particle concentration tested for both dermal and foreskin fibroblasts. The pattern of prostaglandin E2 release by fibroblasts mirrored the pattern of interleukin-6 release. Fibroblasts exposed to the highest concentration of titanium alloy particles showed an increase in collagenase activity, starting at 12 hours. When medium samples were treated with amino phenylmercuric acetate to activate latent enzymes, a statistically significant increase in collagenase activity was observed as early as 6 hours (p < 0.001). Substrate gel analysis of medium from fibroblasts stimulated by high particle concentrations also showed an increase in gelatinolytic activity when compared with unstimulated controls. Analysis of medium samples for growth factors showed an increase in basic fibroblast growth factor at low particle concentrations, beginning at 12 hours. Levels of platelet-derived growth factor-AB and transforming growth factor-beta were not detectable in the controls or at any particle concentration tested. The results of this study showed that fibroblasts exposed to titanium alloy wear particles become activated and release proinflammatory mediators that influence bone metabolism. These data support the hypothesis that direct activation of fibroblasts by particulate wear may play a role in particle-mediated osteolysis. Fibroblast activation coupled with the biologic response of macrophages to wear debris in the loosening membrane may have a synergistic effect on pathologic bone resorption.
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PMID:In vitro activation of human fibroblasts by retrieved titanium alloy wear debris. 867 60


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