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)

Triiodothyronine (T3) increases bone resorption, but its effects on matrix metalloprotease (MMP) expression in bone are unknown. We tested the effects of T3 on collagenase-3 and gelatinase A and B expression in MC3T3 osteoblastic cells. T3 at 1 nM to 1 microM for 24-72 h increased collagenase-3 and gelatinase B mRNA levels, but it did not increase gelatinase A transcripts. In addition, T3 increased immunoreactive collagenase and gelatinase activity. Cycloheximide prevented the stimulatory effect of T3 on collagenase-3 but not on gelatinase B transcripts. Indomethacin did not prevent the effect of T3 on either MMP. T3 did not alter the decay of collagenase-3 or gelatinase B mRNA in transcriptionally arrested MC3T3 cells, and it increased the rate of collagenase-3 and gelatinase B gene transcription. Although T3 enhanced the expression of the tissue inhibitor of metalloproteinase-1 in MC3T3 cells, it increased collagen degradation in cultured intact rat calvariae. In conclusion, T3 increases collagenase-3 and gelatinase B synthesis in osteoblasts by transcriptional mechanisms. This effect may contribute to the actions of T3 on bone matrix remodeling.
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PMID:Triiodothyronine induces collagenase-3 and gelatinase B expression in murine osteoblasts. 1048 62

Cell-cell contact of myeloma-derived cell lines (MDCL) or fresh myeloma cells with bone marrow stromal cells (BMSC) is known to induce interleukin-6 (IL-6) and matrix metalloproteinase-1 (MMP-1) production by a marrow stromal cell line. To determine if other BMSC transcripts are altered during cell-cell contact between BMSC and tumor cells, we have used cell lines ARH77 and U266 in an in vitro model. Using mRNA differential display and reverse transcriptase-polymerase chain reaction (RT-PCR), it was determined that a total of 141 transcripts were either upregulated or downregulated in the BMSC on contact with cell membrane from cell lines ARH77 and U266. Induction of two of these transcripts, interleukin-6 (IL-6) and gp130 in the BMSC by ARH77 cell membranes was studied in greater detail. Real-time PCR was used to quantitate transcript levels of gp130, IL-6, and 36b4, a housekeeping gene. Cycloheximide (CHX) alone increased both gp130 and IL-6 transcripts in the BMSC. In addition, CHX caused a superinduction of these transcripts in BMSC exposed to ARH77 cell membranes. The induction of gp130 was independent of the increase in IL-6 mRNA. Upregulation of gp130, a component of the membrane receptors for the IL-6 superfamily, can have profound effects on the response of BMSC to the IL-6 superfamily of cytokines.
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PMID:Acute activation of gp130 gene expression in bone marrow stromal cells by contact with myeloma-derived lymphoblastic cell line ARH77 cell membranes. 1133 Oct 38

Prostaglandin E2 (PGE2), an abundant eicosanoid in bone, has been implicated in a number of pathological states associated with bone loss, and is also known to stimulate matrix metalloproteinase (MMP)-1 synthesis and secretion in rat and human osteoblast cells, although the nature of the intracellular reaction remains unclear. Although MMP-1 plays a critical role in bone-remodeling, it would be of interest to examine whether PGE2 regulates MMP-1 expression by mouse osteoblasts or not. Here we demonstrate that PGE2 is a potent inducer of MMP-1 production in fetal osteoblasts and show that PGE2 stimulates the activity of the MMP-1 promoter in osteoblasts, suggesting that PGE2 controls MMP-1 gene expression at least at the transcriptional level. PGE2 induced MMP-1 messenger RNA (mRNA) expression in the cells within 4 h, and this expression was maintained for 36 h. The increase in MMP-1 production with 0.1-2.0 microM PGE2 was dose-dependent. We also found that PGE2 (1.5 microM) up-regulated MMP-1 protein levels in cultured mouse osteoblasts, as evidenced by ELISA. To examine whether PGE2 mediated response and signal pathway are involved in the intracellular action, the PGE2-mediated expression of the MMP-1 gene was investigated in mouse osteoblast cells. A Northern blot analysis showed that PGE2 and PGE1 were potent stimulators of MMP-1 transcription, and the presence of thromboxane B2 had no effect. The increase in MMP-1 transcript after PGE2 treatment was observed at 4h, reaching a maximum at 6h, and persisted for 24h. This response was dose-dependent. Cycloheximide, an inhibitor of protein synthesis, completely blocked this effect by PGE2, indicating that the expression of other genes is also required. The second messenger analog, 8-bromo-cAMP, mimicked the effects of PGE2 by stimulating a dose-dependent increase in MMP-1 mRNA levels, with a maximal effect that was quantitatively similar to that observed with PGE2. Thus, the present results strongly suggest that the PGE2 stimulation of MMP-1 synthesis is due to the activation of MMP-1 gene transcription and a subsequent marked increase in MMP-1 transcription. This effect is dependent on de novo protein synthesis and is mimicked by protein kinase A activation. The findings suggest that PGE2 is involved in the cAMP-PKA signaling pathway in regulating MMP-1 gene expression in osteoblasts.
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PMID:PGE2 induces the gene expression of bone matrix metalloproteinase-1 in mouse osteoblasts by cAMP-PKA signaling pathway. 1547 82


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