Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we studied the involvement of BMP-2 and BMP-7 as homodimers and as a mixture of homodimers in bone regeneration using an engineered bone model. The engineered bone model consisted of a collagen scaffold populated with osteoblasts that acted as a carrier for the BMPs. BMP-2, BMP-7 and a mixture of BMP-2/BMP-7 were used at final concentrations of 10 and 100 ng ml(-1). Osteoblasts seeded onto a collagen scaffold were cultured for 24 h before being stimulated with the BMPs. Four days later, osteoblast adhesion to and growth on the scaffold were assessed. Osteocalcin, IL-6, metalloproteinase (MMP-2 and MMP-9) and protease inhibitor (TIMP-1 and TIMP-2) mRNA and protein levels were measured. Our results showed that the BMP-2, BMP-7 and a mixture of BMP-2/BMP-7 all promoted osteoblast growth on the collagen scaffold, with the mixture of BMP-2/BMP-7 enhancing the most growth. BMP-2 and the mixture of BMP-2/BMP-7 enhanced osteocalcin (an osteoblast differentiation marker) mRNA expression and protein secretion, likely via the IL-6 pathway given that IL-6 secretion was upregulated by BMP-7 and a mixture of BMP-2/BMP-7. BMPs promote extracellular matrix production by inhibiting MMP-2 mRNA and increasing TIMP-1 and TIMP-2 mRNA expressions and protein secretions. BMP-2, BMP-7 and the mixture of BMP-2/BMP-7 could promote bone regeneration via different mechanisms involving IL-6 and MMP inhibitors.
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PMID:Effect of BMP-2 and BMP-7 homodimers and a mixture of BMP-2/BMP-7 homodimers on osteoblast adhesion and growth following culture on a collagen scaffold. 1845 95

The aim of this study is to investigate whether BMP-2 regulates the oral sulcus formation of mouse embryonic tongue by modifying the expression of TIMP and MMP. The BMP-2 siRNA induced a 180% increase in the depth of oral sulcus cavity (P < 0.01) by stimulating the invagination of oral sulcus into the mesenchymal tissues consisting of tongue floor, whereas the recombinant BMP-2 suppressed the process in the organ culture system of mouse embryonic tongue. The BMP-2 siRNA induced a 60% decrease in the expression of TIMP-1 mRNA (P < 0.05) and a drastic decline in TIMP-1 protein was observed around the oral sulcus in the BMP-2 siRNA treated mandibles. The recombinant BMP-2 induced a 220% increases in the expression of TIMP-1 mRNA and the area of the immunostaining for TIMP-1 around the oral sulcus was larger in the mandibles treated with the recombinant BMP-2 than the vehicle. The BMP-2 siRNA induced a 60% increase in the expression of MMP-13 protein and a marked increase in the staining intensity for MMP-13 was observed in the epithelial region of the BMP-2 siRNA treated mandibles. The recombinant BMP-2 induced a 70% decrease in the expression of MMP-13 mRNA and the decrease was mainly observed in the tissues around oral sulcus. The expressions of BMP-2, TIMP-1, and MMP-13 were verified in the tissues around in vivo developing oral sulcus at E11, 12, and 13 by immunohistochemistry. These results suggest that BMP-2 regulates the formation of oral sulcus by altering the balance between TIMP-1 and MMP-13.
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PMID:BMP-2 regulates the formation of oral sulcus in mouse tongue by altering the balance between TIMP-1 and MMP-13. 2066 18

Matrix metalloproteinase-9 (MMP-9) plays a central role in the progression of the cancer. While a large number of studies have contributed to our understanding of the molecular mechanisms responsible for upregulating MMP-9 gene expression in normal and cancer cells, our knowledge on the signals that suppress MMP-9 expression is much more limited. Here, we report that EGF and BMP-4 cooperate to inhibit MMP-9 expression in cancer cells. Treatment with EGF reduces the expression of MMP-9 at both mRNA while augmenting BMP-4 expression. Interestingly, recombinant BMP-4 suppressed constitutive and PMA-induced MMP-9 expression in both fibrosarcoma and breast cancer cells. Addition of gremlin a natural inhibitor of BMP-4, inhibited the suppression of MMP-9 by EGF. The suppression of MMP-9 by BMP-4 likely occurs at the transcriptional level since BMP-4 suppressed MMP-9 mRNA expression and activation of a reporter vector encoding the human MMP-9 promoter. The suppressive effect of BMP-4 occurs via Smad1/5/8 and is specific since BMP-4 did not inhibit MMP-2 while BMP-2 was ineffective in suppressing MMP-9. Taken together, these results are consistent with a new paradigm for the role of EGF and BMPs in controlling MMP gene expression in cancer cells.
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PMID:Bone morphogenetic protein 4 (BMP-4) and epidermal growth factor (EGF) inhibit metalloproteinase-9 (MMP-9) expression in cancer cells. 2589 33