Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the mouse, arthritis was induced by a single sub-patellar intraarticular injection of bacterial collagenase. This procedure induces also patellar malalignment. A rich innervation of thin varicose calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactive fibers was found in the joint capsule, in the periosteum of the patella, in the synovial tissues at the lateral border of the patella, in the femoral groove, and in the subchondral bone of the patella and femur. Moreover, fibers were found in plica tissues between the quadriceps and patellar tendon, and the femoral groove. After the collagenase treatment, the general innervation pattern was comparable to that of the controls, but CGRP and SP innervation was no longer detectable with the antibodies in the plica tissues, and was to a lesser extent detectable in the fat pad of the patella, in the lateral borders of the patella and in the proliferated synovial tissues. Signs of degenerated axonal profiles were observed in these locations with a polyclonal antibody to the growth-associated protein GAP-43/B-50. At all the other peripheral locations, such as the muscles, the GAP-43/B-50 distribution was normal.
...
PMID:Innervation of the patella. An immunohistochemical study in mice. 751 3

Although the osteocyte is the most abundant among the highly differentiated cells of mature bone (osteocytes, lining cells, osteoblasts, and osteoclasts), its properties and functions are the least known and understood. Here we isolated osteocytes from mixed populations of bone cells liberated from fetal chick calvariae by alternate treatments with collagenase and EDTA. The osteocytes were removed from the bone cell populations by binding them via an osteocyte-specific antibody (MAb OB 7.3) to magnetic beads and removing the beads together with the coupled osteocytes from the population using a magnet. Isolated osteocytes were found to be highly differentiated, postmitotic cells that required their typical stellate morphology in culture. Osteocyte populations had alkaline phosphatase (ALP) activity somewhat lower than that of the osteoblast-like cell populations from which they were separated by the immunodissection procedure. On the single-cell level, the ALP activity was highly variable. Parathyroid hormone (PTH) receptors were found to be present on osteocytes as well as on osteoblast-like cells, but not on fibroblast-like cells of the outer periosteum. In response to PTH, osteocytes increased their intracellular levels of cAMP, as did the osteoblast-like cells. Osteocytes appeared to be somewhat more sensitive to PTH than osteoblasts. When seeded onto dentin slices, osteocytes did not corrode the dentin surface to any appraisable degree. We therefore found no evidence to support the notion that osteocytes play a role in the calcium homeostasis through osteocytic osteolysis. Whether osteocytes play an important role in perceiving and transducing hormonal and/or mechanical stimuli remains open for future research.
...
PMID:Characteristics and properties of osteocytes in culture. 786 20

The effect of interleukin-1 alpha (IL-1 alpha) and murine epidermal growth factor (EGF) on incorporation of endogenously produced collagenase in the extracellular matrix of soft connective tissue was studied in an in vitro model system using periosteal explants obtained from rabbit calvariae. Immunohistochemical analysis indicated the highest level of collagenase in explants cultured for 72 hours with IL-1 alpha in combination with EGF. Most enzyme appeared to be associated with the extracellular matrix, but labeling was also found in numerous fibroblast-like cells. Explants cultured in the presence of IL-1 alpha alone contained less enzyme and in periostea treated without cytokines, or with EGF alone, only a faint label, if any, was seen. Freshly isolated, non-cultured periostea contained no detectable enzyme. Extraction of collagenase from periostea revealed that: (1) non-cultured periosteum did not contain detectable levels of enzyme. (2) The amount of total activatable enzyme synergistically increased (10-fold) under the influence of IL-1 alpha and EGF, whereas IL-1 alpha alone showed a 4-fold enhancement compared to control or EGF-incubated explants. (3) The latent fraction of the enzyme was synergistically increased (up to 100-fold or more) in periostea cultured in the presence of IL-1 alpha + EGF (21.17 mU/explant versus 0.05 mU/explant in controls). (4) Active collagenase, on the other hand, appeared to be present in a relatively high concentration in explants cultured without cytokines (2.45 mU/explant versus 0.36 mU/explant in IL-1 alpha + EGF-treated explants).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Immunolocalisation of collagenase in rabbit periosteal tissue explants and extraction of the enzyme. The effect of the cytokines IL-1 alpha and EGF. 805 29

Tissue inhibitors of metalloproteinases (TIMPs) play an important role in the regulation of the activity of matrix metalloproteinases (MMPs) such as collagenase, stromelysin and gelatinase. Although it has been shown that upon culturing bone tissue releases relatively large amounts of TIMP, little is known as to the source of the inhibitor. In an attempt to investigate this in more detail calvarial bone explants from young rabbits were cultured in serum-free medium. The explants were cultured with or without adhering periosteum. In some experiments solitary periosteal fragments were maintained in the absence of bone. Media were analyzed for the presence of TIMP by immunoblotting and ELISA as well as for their capacity to inhibit the activity of collagenase. In addition, TIMP was immunolocalized in cryosections of the explants. The data demonstrated that bone-conditioned medium contained significantly more (2-10 times) collagenase inhibitor than periosteum-conditioned medium. Removal of the (convex and/or concave) periosteum from the calvariae did not significantly affect the amount of inhibitor released. Immunoblots and ELISA showed the presence of TIMP in the media, being more in bone- than in periosteum-conditioned medium. In immunolabeled cryosections TIMP appeared to be present in osteoblast-like cells lining both the outer bone surface as well as the endosteal spaces. Label was also found in a number of osteocyte lacunae. The periosteum was almost negative. It is suggested that TIMP contributes to the regulation of MMP-activity involved in the remodeling and turnover of bone.
...
PMID:The release of tissue inhibitor of metalloproteinases by calvarial bone explants and its immunolocalization. 821 37

Endosteal bone surface cells were previously shown to be involved in the regulation of bone formation in humans. In this study, we have characterized the cells isolated from the endosteal bone surface in adult rats. Fragments of periosteum-free tibia were obtained from 4-, 6- and 9-month-old rats by collagenase digestion, and the phenotypic characteristics of the osteoblastic cells migrating from the endosteal bone surface were evaluated in culture. Endosteal bone surface cells present a strong alkaline phosphatase (ALP) activity as shown by cytochemistry and measured biochemically. The cells synthesize high levels of osteocalcin as measured by radioimmunoassay. Osteocalcin production was increased after stimulation with 10 nM 1,25 dihydroxyvitamin D (1,25(OH)2 D) and the response to 1,25(OH)2 D was similar at all ages. Endosteal cells from young adult rats (4 months old) but not from older rats (6 and 9 months old) showed increased cAMP production in response to 10 nM parathyroid hormone (PTH), suggesting an age-related decrease in the PTH-responsiveness of the bone surface cells. Immunocytochemistry using specific antibodies showed that preconfluent endosteal bone cells from adult rats expressed collagen and noncollagenous bone proteins in culture in the absence of inducers. The cells synthesized mostly type-I collagen which remained localized intracellularly. Type-III collagen was only expressed at low levels. The bone surface cells also expressed osteocalcin and bone sialoprotein, two markers of differentiated osteoblasts, as well as osteonectin.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Cells isolated from the endosteal bone surface of adult rats express differentiated osteoblastic characteristics in vitro. 847 7

Plasminogen activators (PA) are implicated in cell migration and tissue remodeling, two components of the bone resorption processes. Using mice with inactivated tissue PA (tPA), urokinase PA (uPA), or type 1 PA inhibitor (PAI-1) genes, we evaluated whether these processes, or their stimulation by parathyroid hormone (PTH) or 1,25-dihydroxyvitamin (1,25[OH]2D3) are dependent on these genes. Two culture models were used, one involving 19-day fetal calvariae, to evaluate the direct resorptive activity of osteoclasis, and the other involving 45Ca-labeled 17-day fetal metatarsals, in which this activity depends on preliminary (pre)osteoclast migration. PTH similarly increased (about 10-fold) PA activity in calvariae from wild-type tPA+/+ and uPA+/+ or deficient uPA-/- and PAI-/- mice; it affected only tPA, not uPA. In tPA-/- bones, the low PA levels, due to uPA, were not influenced by PTH. Calcitonin did not affect PA responses to PTH. No differences were observed between tPA+/+, tPA-/-, uPA+/+, and uPA-/- calvariae for any parameter related to bone resorption (development of lacunae, release of calcium and lysosomal enzymes, accumulation of collagenase, loss of hydroxyproline), indicating similar responses to PTH or calcitonin. The progressive 45Ca release was largely similar in cultures of tPA+/+, tPA-/-, uPA+/+, uPA-/-, PAI+/+, or PAI-/- metatarsals and it was similarly enhanced by PTH or 1,25(OH)2D3. However, uPA-/- metatarsals released 45Ca at a slower rate at the beginning of the cultures, suggesting an impaired recruitment of the (pre)osteoclasts, which migrate at that time from the periosteum into the calcified cartilage. Thus, it appears that the direct resorptive activity of the osteoclasts does not necessitate the presence of either tPA or uPA, but uPA is likely to facilitate the migration of the (pre)osteoclasts toward the mineralized surfaces. Although considerably enhanced by PTH, tPA does not mediate the actions of PTH (nor of 1,25[OH]2D3) evaluated in these models.
...
PMID:Bone resorption and response to calcium-regulating hormones in the absence of tissue or urokinase plasminogen activator or of their type 1 inhibitor. 885 51

Other than its known effects on the cardiovascular system, angiotensin II (Ang II) stimulates cell growth in several cell types. In this study, we examined whether it also might affect bone cell metabolism. Ang II stimulated DNA and collagen synthesis and decreased alkaline phosphatase (AP) activity in bone cell populations derived from the periosteum of fetal rat calvariae. Similar effects of Ang II were observed on human adult bone cells obtained by collagenase digestion from trabecular bone. Clonal cell analysis, autoradiographic studies, and receptor subtype analysis suggested the presence of specific Ang II receptor subtype 1 (AT1) binding sites on AP+ osteoblastic precursor cells. Ang II had no direct effects on osteoblastic cells with a mature phenotype, but paracrine effects of Ang II on mature osteoblasts could be observed upon coculture with Ang II-responsive bone cell populations. Because Ang II is known to be locally generated by endothelial cells, Ang II might play an important role in coordinating capillary cell growth and osteoblastic bone formation during bone remodeling.
...
PMID:Effects of angiotensin II on bone cells in vitro. 949 84

Matrix metalloproteinases (MMPs), among which is collagenase (MMP-1), are likely to be involved in various steps of the bone resorption process. As both production of these enzymes and bone resorption appear to be mediated by cytokines, we investigated the effects of two cytokines, IL-1 alpha and EGF, on the release of collagenase, gelatinase A (MMP-2), gelatinase B (MMP-9), TIMP-1 and calcium by rabbit calvariae. It was found that all these parameters increased under the influence of these cytokines. The release of calcium--used as a parameter of bone resorption--was highest in the combined presence of the cytokines. Although the absolute and relative enhancement by a combination of IL-1 alpha and EGF was most pronounced for collagenase (7-fold), both gelatinase A (5-fold) and gelatinase B (1.5-fold) had increased simultaneously. Calvariae produced a high level of MMP inhibitor (TIMP-1), especially under the influence of the cytokines; periosteum released little inhibitor. It is concluded that IL-1 alpha and EGF are likely to play a modulating role in the process of bone resorption.
...
PMID:EGF and IL-1 alpha modulate the release of collagenase, gelatinase and TIMP-1 as well as the release of calcium by rabbit calvarial bone explants. 952 23

Parathyroid hormone (PTH) stimulates bone resorption by acting directly on osteoblasts/stromal cells and then indirectly to increase differentiation and function of osteoclasts. PTH acting on osteoblasts/stromal cells increases collagenase gene transcription and synthesis. To assess the role of collagenase in the bone resorptive actions of PTH, we used mice homozygous (r/r) for a targeted mutation (r) in Col1a1 that are resistant to collagenase cleavage of type I collagen. Human PTH(1-34) was injected subcutaneously over the hemicalvariae in wild-type (+/+) or r/r mice four times daily for three days. Osteoclast numbers, the size of the bone marrow spaces and periosteal proliferation were increased in calvariae from PTH-treated +/+ mice, whereas in r/r mice, PTH-induced bone resorption responses were minimal. The r/r mice were not resistant to other skeletal effects of PTH because abundant interstitial collagenase mRNA was detected in the calvarial periosteum of PTH-treated, but not vehicle-treated, r/r and +/+ mice. Calcemic responses, 0.5-10 hours after intraperitoneal injection of PTH, were blunted in r/r mice versus +/+ mice. Thus, collagenase cleavage of type I collagen is necessary for PTH induction of osteoclastic bone resorption.
...
PMID:Bone resorption induced by parathyroid hormone is strikingly diminished in collagenase-resistant mutant mice. 1002 60

In the present study we investigated whether the collagen types I, III and V affect the activity of fibroblasts obtained from rabbit periosteum. The cells were cultured on plates either or not coated with different amounts of collagen type I, III or V and analyzed for their attachment, DNA synthesis and the expression and activity of matrix metalloproteinases (MMPs). Our data show that the three collagen types promoted attachment and spreading of the cells and stimulated DNA synthesis when used in relatively low concentrations. High concentrations of type V-but not of type I or III-proved to inhibit thymidine incorporation. The expression and activity of matrix metalloproteinase 1 (MMP-1; interstitial collagenase) decreased under the influence of relatively low amounts of collagen (<40 microg/well), whereas higher levels increased its release. Matrix metalloproteinase 2 (MMP-2; gelatinase A) was up-regulated by the different types of collagen; the active fraction of stromelysin-1 (MMP-3) decreased. Accordingly, the mRNA expression of MMP-1 and -3 were reduced. The expression of MMP-2 mRNA, however, proved to be unaffected. Blocking antibodies to beta(1)-integrin or echistatin increased the level of MMP-1 but had no effect on MMP-2. All parameters tested were similarly affected by type I and III collagen, whereas the effect of type V was always less. We conclude that the collagen types I, III and V provide different sets of signals for fibroblasts that differently modulate their proliferation and MMP expression.
...
PMID:Collagen type I, III and V differently modulate synthesis and activation of matrix metalloproteinases by cultured rabbit periosteal fibroblasts. 1285 32


<< Previous 1 2 3 4 Next >>

---