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

Perinatal rat calvarial bone cells were isolated by sequential collagenase digestion and grown in oxygen tensions ranging from 1 to 60% O2. Cell proliferation as determined by automated cell counting and DNA content was greatest in the lower oxygen tensions (less than or equal to 9% O2), whereas alkaline phosphatase activity and [35S]sulfate and [14C]proline incorporation were greatest in the higher oxygen tensions (greater than or equal to 13% O2). It is concluded that lower oxygen concentrations favor bone cell proliferation, whereas higher oxygen concentrations favor macromolecular synthesis. These findings, when related to the known pO2 of the fracture callus, suggest the following sequence of events: first, at the time of fracture an ingrowth of osteoprogenitor cells, capillary buds, and primitive mesenchymal cells occurs in the fracture site, a region of low pO2; second, a great increase in cellular proliferation accompanied by an initiation of macromolecular synthesis follows; finally, as the pO2 levels begin to increase, cellular proliferation decelerates, accompanied by an increase in macromolecular synthesis.
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PMID:Proliferation and macromolecular synthesis by rat calvarial bone cells grown in various oxygen tensions. 191 47

Implantation of rat demineralized bone matrix into intramuscular pouches has been shown to cause a complex cellular transition of mesenchymal-type cells into well developed mature bone. Demineralized bone matrix was surgically implanted into rat muscle pouches and removed at various intervals between 7 and 28 days. Histological sections of the implants revealed bone formation by endochondral ossification and appositional bone growth. Biochemical analysis of collagen synthesis demonstrated the following: (1) synthesis of type X collagen, a collagen produced by hypertrophic chondrocytes in the growth plate and in fracture callus. (2) Synthesis of a collagenase-sensitive 17k protein which seems to increase in the early stages of bone induction. Pulse chase analysis indicates that 17k is not a degradation product of another protein and appears to be synthesized without a large Mr precursor. The 17k component contains one or more collagenous domains that are partially resistant to proteolysis with pepsin. Our results confirm the appearance of a cartilage intermediate during demineralized bone matrix induced ossification and implicate the existence of proteins which may be useful markers in future studies on matrix mineralization and ossification.
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PMID:Bone induction in intramuscular implants by demineralized bone matrix: sequential changes of collagen synthesis. 322 99

The morphologic events and macromolecular interactions in matrix-induced bone formation are comparable with those occurring in the development of fracture callus. Thus, bone induction by decalcified bone matrix is an experimental model for fracture healing and a new tool for research concerning the biochemistry of bone cell differentiation. Three conditions are necessary for bone cell differentiation in postnatal life: (1) a three-dimensional pattern of proliferation of mesenchymal cells; (2) anchorage-dependent microvilli extending the proliferating cells; and (3) a locally released bone morphogenetic protein (BMP). To date, BMP with a molecular weight of 17,500-18,500 daltons has been isolated from bone, and a BMP-like protein with a molecular weight of 22,000 daltons has been extracted from mouse osteosarcoma. It is difficult to separate BMP, a collagenase-resistant, trypsin-labile acidic polypeptide, from several other low molecular weight proteins.
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PMID:Postnatal new bone formation. 670 31

Interstitial collagenase plays an important role in both the normal and pathological remodeling of collagenous extracellular matrices, including skeletal tissues. The enzyme is a member of the family of matrix metalloproteinases. Only one rodent interstitial collagenase has been found but there are two human enzymes, human collagenase-1 and -3, the latter being the homologue of the rat enzyme. In developing rat and mouse bone, collagenase is expressed by hypertrophic chondrocytes, osteoblasts, and osteocytes, a situation that is replicated in a fracture callus. Cultured osteoblasts derived from neonatal rat calvariae show greater amounts of collagenase transcripts late in differentiation. These levels can be regulated by parathyroid hormone (PTH), retinoic acid, and insulin-like growth factors, as well as the degree of matrix mineralization. Much of the work on collagenase in bone has been derived from studies on the rat osteosarcoma cell line, UMR 106-01. All bone-resorbing agents stimulate these cells to produce collagenase mRNA and protein, with PTH being the most potent stimulator. Determination of secreted levels of collagenase has been difficult because UMR cells, normal rat osteoblasts, and rat fibroblasts possess a scavenger receptor that removes the enzyme from the extracellular space, internalizes and degrades it, thus imposing another level of control. PTH can also regulate the abundance of the receptor as well as the expression and synthesis of the enzyme. Regulation of the collagenase gene by PTH appears to involve the cAMP pathway as well as a primary response gene, possibly Fos, which then contributes to induction of the collagenase gene. The rat collagenase gene contains an activator protein-1 sequence that is necessary for basal expression, but other promoter regions may also participate in PTH regulation. Thus, there are many levels of regulation of collagenase in bone perhaps constraining what would otherwise be a rampant enzyme.
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PMID:The regulation and regulatory role of collagenase in bone. 888 5