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)

Femurs from 9-day-old embryo were cultured for 4 days by the roller-tube method in the presence of Cd and/or Cu. The combination of both Cd and Cu caused a significantly interactive decrease in hydroxyproline (Hyp) synthesis as well as bone growth compared with that in the presence of Cd (1.1 or 3.3 microM) or Cu (1.1 or 2.2 microM) alone. The presence of both 2.2 microM Cd and 3.3 microM Cu also showed a significantly interactive decrease in the incorporation of [3H]proline (Pro) into collagenase-digestible protein (CDP), but it showed no interactive inhibition of the hydroxylation of [3H]Pro in CDP. The two metals were also interactive with respect to the inhibition of the synthesis of protein, RNA and DNA. Culture of epiphysis in the presence of both Cd and Cu resulted in higher content of Cd and Cu compared to those cultured in Cd or Cu alone. Subcellular fractions from epiphysis cultured in Cd plus Cu contained more Cd than those cultured in Cd alone. Cu was increased in two fractions, nuclei and cytosol, following co-incubation. The cytosol from epiphysis cultured in the presence of both Cd and Cu contained more Cd in both a metallothionein (MT)-like protein and a high-molecular-weight (HM) protein than cytosol from Cd-treated bones. The amount (nmol) of Cu in the MT fraction was nearly equal to the sum of the increased amounts (nmol) of Cd in HM fraction of cytosol and particulate fractions. This indicates that some Cd in MT-like protein induced by Cd is replaced with Cu and the released Cd redistribution to HM fraction and particulate fractions. Most of the Cd in the solubilized particulate fractions was detected in the HM fraction. A marker enzyme or component in each fraction was interactively inhibited by both Cd and Cu. Therefore, the interactive inhibition of bone metabolism by both Cd and Cu in the cultured bone is at least partly due to the increase in Cd content of HM fraction of cytosol and particulate fractions.
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PMID:A possible mechanism of cadmium-copper interaction in embryonic chick bone in tissue culture. 243 15

Although it has been reported that interleukin 1 (IL-1) stimulate chondrocytes to produce collagenase and proteoglycanase in vitro, IL-1 producing cells and the function of IL-1 have not been demonstrated in osteocartilaginous tissue in vivo. Immunohistochemical studies of human cartilaginous epiphysis and growth cartilage demonstrated that IL-1 was detected in: (1) chondrocytes surrounding cartilage canal, (2) hypertrophic chondrocytes in cartilaginous epiphysis, (3) chondrocytes at the hypertrophic and calcified zones in the growth cartilage of actively growing bone. In contrast, few hypertrophic chondrocytes showed positive reactions to IL-1 in growth plates nearing physiologic closure. Furthermore, IL-1 was detected in chondrocytes cultured from human growth cartilage. These results show that IL-1 is produced by matured chondrocytes of human growth cartilage in vivo. Chondrocyte-derived IL-1 might play a key role in the hypertrophy of chondrocytes, in the vascularization of cartilage and in the formation of bone.
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PMID:Immunohistochemical localization of interleukin 1 in human growth cartilage. 279 32

Tetracyclines (including the semi-synthetic analogues, minocycline and doxycycline) are considered useful adjuncts in periodontal therapy because they suppress Gram-negative periodontopathogens. Recently, these antibiotics were found to inhibit mammalian collagenase activity, a property which may also be of therapeutic value. It has been suggested that the anti-collagenase properties of the tetracyclines are independent of their antibiotic efficacy. To advance this hypothesis further, we chemically converted tetracycline hydrochloride to its non-antimicrobial analogue, de-dimethylaminotetracycline. This chemically-modified tetracycline (CMT), although no longer an effective antibiotic, was found to inhibit the in vitro activity of collagenase from partially purified extracts of human rheumatoid synovial tissue and rachitic rat epiphysis. In a preliminary in vivo study, pathologically-excessive collagenase in skin and gingiva was induced by rendering adult male rats diabetic, and the oral administration of CMT to these rats significantly reduced the excessive collagenase activity in both tissues. Moreover, CMT administration did not affect the severe hyperglycemia in these rats but did prevent, at least in part, the diabetes-induced loss of body weight, skin weight, and skin collagen mass; these effects suggest a lack of toxicity in this animal model. A proposed clinical advantage of CMT over conventional tetracyclines, in the treatment of diseases characterized by excessive collagenolytic activity, is the lack of development of antibiotic-resistant micro-organisms during prolonged use. However, the consideration of clinical trials to support this hypothesis must await further laboratory and extensive toxicity tests.
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PMID:A non-antibacterial chemically-modified tetracycline inhibits mammalian collagenase activity. 304 Aug 32

An original and reliable technique to culture growth plate chondrocytes was developed to obtain an abundant amount of mature and functional chondrocytes. Growth plates were provided from the epiphysis of 3 week old rabbits. The isolation of the chondrocytes was optimized by the use of trypsin and collagenase. The culture was realized according to the following conditions: seeding at 20,000 or 30,000/cm2 on type I collagen substrate and in Ham F12 medium without a supplementation of glucose or growth factors. After 7 days of culture, the implantation was to be carried out. Different implantation substrates were evaluated in vivo. Agar turned out to be the only substrate to provide strong and healthy chondrocytes 21 days after the grafting. In an other experimentation, the culture was implanted into surgically created defects in the growth plate area. In this case, the culture did not avoid the occurrence of an epiphysiodesis. However, the 6 weeks post operative histologic examination, showed that the implant remained viable, continued to maintain a proteoglycan rich matrix, and began to organize in ordered columns of mature chondrocytes.
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PMID:[In vitro culture of growth cartilage and in situ reimplantation]. 894 14

Growth plate lesions or resections may cause severe growth arrest because of the bony bridge between the epiphysis and metaphysis. Actual treatments for epiphysiodesis include resecting the bone bar and setting an interpositional material. Growth plate cultures may provide the appropriate cartilage necessary to restore growth potential when implanted in a growth plate defect. The aim of this work was to determine certain cell culture parameters in order to optimize in vitro cultures to obtain abundantly mature and functional chondrocytes. We studied the manner in which enzymatic digestion, carried out by various enzymes, obtained chondrocytes. Treatment with trypsin (0.2%) during 30 minutes at 37 degrees C and then collagenase (200 U/mL) during 6 hours was chosen. Under these conditions, 40 +/- 16 10(6) chondrocytes per gram of growth plate were obtained, and cellular viability was 79 +/- 12%. The density of the cellular seeding, the nature of the culture substrate, and the culture medium composition were determined to optimize the growth of differentiated cells. Seeding at 20,000 or 30,000/cm2 on a type I substrate and Ham F-12 medium not supplemented with either glucose or growth factors was demonstrated to be the best choice for this purpose.
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PMID:Reimplantation of growth plate chondrocyte cultures in central growth plate defects: Part I. Characterization of cultures. 959 97

An original and reliable technique to culture growth plate chondrocytes was developed to obtain an abundant amount of mature and functional chondrocytes. Growth plates were provided from the epiphysis of 3-week-old rabbits. Isolation of the chondrocytes was optimized by the use of trypsin and collagenase. The culture was realized according to the following conditions: seeding at 20,000 or 30,000/cm2 on type I collagen substrate and in Ham F-12 medium without a supplementation of glucose or growth factors. After 7 days of culture, the implantation was to be carried out. Different implantation substrates were evaluated in vivo. Agar turned out to be the only substrate to provide strong and healthy chondrocytes 21 days after the grafting. Then implantation was tested on large iliac resections in rabbits to check whether an enchondral ossification occurred with the culture. Poor results were obtained because of an early disappearance of the cultured chondrocytes. In an other experimentation, the culture was implanted into surgically created defects in the growth plate area. In this case, the culture did produce an epiphysiodesis. However, the 6-week postoperative histological examination showed that the implant remained viable, continued to maintain a proteoglycanrich matrix, and began to organize in ordered columns of mature chondrocytes.
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PMID:Reimplantation of growth plate chondrocyte cultures in central growth plate defects: Part II. Surgical experimentation in rabbits. 959 98

The interepiphyseal region between the greater trochanter and the capital femoral epiphysis and the medioproximal portion of the femoral neck exhibit extensive morphological changes during the first 4 weeks after birth in rats. Previous reports show that matrix metalloproteinase-13 (MMP-13, rat collagenase) mRNA is expressed in bone and cartilage during embryonal development and fracture healing. We examined MMP-13 mRNA expression and compared it with the distribution of osteopontin and osteocalcine mRNA in the femoral neck. Moreover, we examined histomorphometric analysis in the femoral neck where the morphology changes rapidly. Histomorphometric analysis of the 4-week-old rat femoral neck showed a high rate of bone formation and resorption in the region where shape changed rapidly. Osteopontin mRNA was expressed diffusely along the endosteum. In contrast, MMP-13 mRNA expression was restricted to the medial endosteal portion near the cartilage-bone interface of the femoral neck in 15- and 28-day-old rats and in the deepest endosteal interepiphyseal region of 15-day-old rats. MMP-13 mRNA-expressing osteoblastic cells were also expressing osteopontin but not osteocalcin mRNA. MMP-13 mRNA-expressing cells differ from tartrate-resistant acid phosphatase (TRAP)-positive cells, and MMP-13 mRNA-positive cells are located adjacent to TRAP-positive cells. The results of the site- and cell-specific expression of MMP-13, taken together with its enzymatic property, suggest that MMP-13 plays an important role in morphological changes in the rat femur, at least during the third and fourth week after birth, and that MMP-13 itself is involved in the interaction between osteoblastic and TRAP-positive cells.
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PMID:Spatiotemporal change of rat collagenase (MMP-13) mRNA expression in the development of the rat femoral neck. 1087 97

In the past few years there has been a considerable interest in the role of bone in osteoarthritis. Despite the increasing evidence of the involvement of bone in osteoarthritis, it remains very difficult to attribute the cause or effect of changes in subchondral bone to the process of osteoarthritis. Although osteoarthritis in mice provides a useful model to study changes in the subchondral bone, detailed quantification of these changes is lacking. Therefore, the goal of this study was to quantify subchondral bone changes in a murine osteoarthritis model by use of micro-computed tomography (micro-CT). We induced osteoarthritis-like characteristics in the knee joints of mice using collagenase injections, and after four weeks we calculated various 3D morphometric parameters in the epiphysis of the proximal tibia. The collagenase injections caused cartilage damage, visible in histological sections, particularly on the medial tibial plateau. Micro-CT analysis revealed that the thickness of the subchondral bone plate was decreased both at the lateral and the medial side. The trabecular compartment demonstrated a small but significant reduction in bone volume fraction compared to the contralateral control joints. Trabeculae in the collagenase-injected joints were thinner but their shape remained rod-like. Furthermore, the connectivity between trabeculae was reduced and the trabecular spacing was increased. In conclusion, four weeks after induction of osteoarthritis in the murine knee subtle but significant changes in subchondral bone architecture could be detected and quantified in 3D with micro-CT analysis.
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PMID:Quantification of subchondral bone changes in a murine osteoarthritis model using micro-CT. 1691 10