A new synthetic inhibitor of mammalian tissue collagenase inhibits bone resorption in culture

Delaissé, Jean‐Marie; Eeckhout, Yves; Sear, Christopher H. J.; Galloway, A; McCullagh, K.G.; Vaes, Gilbert

doi:10.1016/0006-291x(85)90932-5

Cited by 94 publications

(39 citation statements)

References 28 publications

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“…Of the known neutral matrix metalloproteinases, interstitial collagenase has been reported to be produced by rodent osteoblasts under certain conditions (13,15,(31)(32)(33) and has been found associated with bone matrix proteins and possibly osteoclasts (11). To determine if interstitial collagenase was the metalloproteinase involved in initiating bone resorption, we treated the marrow cultures with a rabbit antiserum specific for rodent collagenase (anti-rIC; 34), which inhibits its enzymatic activity (34,35).…”

Section: Resultsmentioning

confidence: 99%

“…Although some prior studies suggested that neutral metalloproteinases contribute to osteoclast matrix degradation (11), recent evidence indicates that osteoclasts do not produce collagenase (12). Collagenase is produced by cells of osteoblastic lineage and may be required for resorption of intact bone tissue (13)(14)(15)(16). Observations that isolated osteoclasts that had no detectable collagenase activity were able to resorb bone prompted the suggestion that collagenase promotes resorption by removing unmineralized matrix from the bone surface, facilitating osteoclast attachment (8,17,18).…”

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confidence: 99%

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Initiation of Osteoclast Bone Resorption by Interstitial Collagenase

Holliday¹,

Welgus²,

Fliszar³

et al. 1997

Journal of Biological Chemistry

224

167

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Osteoclasts form an acidic compartment at their attachment site in which bone demineralization and matrix degradation occur. Although both the cysteine proteinases and neutral collagenases participate in bone resorption, their roles have remained unclear. Here we show that interstitial collagenase has an essential role in initiating bone resorption, distinct from that of the cysteine proteinases. Treatment of osteoclasts with cysteine proteinase inhibitors did not affect the number of resorption lacunae ("pits") formed on the surface of dentine slices, but it generated abnormal pits that were demineralized but filled with undegraded matrix. Treatment with metalloproteinase inhibitors did not alter the qualitative features of lacunae, but it greatly reduced the number of pits and surface area resorbed. Treatment of bone cells with an inhibitory anti-rat interstitial collagenase antiserum reduced bone resorption markedly. In the presence of collagenase inhibitors, resorption was restored by pretreatment of dentine slices with rat interstitial collagenase or by precoating the dentine slices with collagenase-derived gelatin peptides or heatgelatinized collagen. Immunostaining revealed that interstitial collagenase is produced at high levels by stromal cells and osteoblasts adjacent to osteoclasts. These results indicate that interstitial collagenase can function as a "coupling factor," allowing osteoblasts to initiate bone resorption by generating collagen fragments that activate osteoclasts.Normal bone turnover is highly regulated. Osteoclasts, the cells that degrade bone, require activation to trigger their boneresorptive capacity. Once activated, osteoclasts secrete both protons and proteinases at their attachment site, resulting in dissolution of bone mineral and degradation of the matrix (1). Osteoclasts produce several cysteine proteinases (2-4), enzymes with acidic pH optima, of which cathepsin K appears to be essential for normal bone resorption (5, 6). Studies indicate that the major function of secreted cysteine proteinases is matrix degradation (3, 7).The role of neutral metalloproteinases, a second class of proteinase produced in bone tissue (3,8), is less clear. Members of the metalloproteinase family have neutral pH optima, are secreted as proenzymes, and contain a zinc atom at the active site (9, 10). Although some prior studies suggested that neutral metalloproteinases contribute to osteoclast matrix degradation (11), recent evidence indicates that osteoclasts do not produce collagenase (12). Collagenase is produced by cells of osteoblastic lineage and may be required for resorption of intact bone tissue (13)(14)(15)(16). Observations that isolated osteoclasts that had no detectable collagenase activity were able to resorb bone prompted the suggestion that collagenase promotes resorption by removing unmineralized matrix from the bone surface, facilitating osteoclast attachment (8,17,18).In this study we have examined the qualitative and quantitative roles of acid cysteine proteinases and interstitial...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Initiation of Osteoclast Bone Resorption by Interstitial Collagenase

Holliday¹,

Welgus²,

Fliszar³

et al. 1997

Journal of Biological Chemistry

224

167

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“…8). Delaissè et al (1985) and Gillet et al (1977) added high sodium chloride concentrations (up to one M) during extraction to encourage the dissociation of collagenase from insoluble collagen. Ohyama and Hashimoto (1977) incorporated repetitive freeze-thaw cycles to disrupt cell walls and make the enzyme more accessible to the buffer.…”

Section: Tris-hcl Buffer Extractionmentioning

confidence: 99%

“…Dissociation of collagenase from insoluble collagen was carried out using high NaCl concentrations while the cacodylate buffer demineralizes the bones to release the collagenase. Calcium was omitted but a non-ionic detergent was used to stabilize the extracted collagenase (Gillet et al, 1977;Delaissè et al, 1985). This method reported for the first time the isolation of procollagenase from the bone.…”

Section: Cacodylate Buffer Extractionmentioning

confidence: 99%

Extraction and Purification of Collagenase Enzymes: A Critical Review

Daboor¹,

Budge²,

Ghaly

et al. 2010

American Journal of Biochemistry and Biotechnology

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Problem statement: Enzymes have vital roles in several industrial processes (foods, cosmetics, nutraceuticals and pharmaceuticals) due to their highly selective nature and high activity at very low concentrations. Recent efforts to identify new sources of useful enzymes have been concentrated on the marine environment because of the potential to make use of processing wastes. About 35-50% of the mass of the fish caught is a waste that is disposed off at sea or in landfills. The extraction of enzymes from fish processing waste can reduce environment problems and improve the economics of the fish industry. Collagenases are a group of enzymes that can be extracted from fish waste. Approach: Comprehensive reviews of the literature on the extraction, purification, characterization and use of collagenases was carried out. Results: Collagenases have different molecular weights based on their types and sources. They have the ability to break down the peptide bonds in collagen at physiological pH. They are classified into two types: serine and metallocollagenase. Collagenolytic activities have been shown at a wide range of temperatures (20-40°C) and pH (6-8). Many activators can be used to achive collagenase activity including 4-Aminophenylmercuric Acetate (APMA), trypsin, potassium or sodium thiocyanate, iodoacetamide and potassium iodide. Dithiothreitol (DTT), mercaptoethanol, ethylendiaminetetracetic acid, ophenanthroline and cysteine inactivate the enzyme. Collagenases enzymes can be extracted with a variety of techniques using different buffering systems (tris-HCl, sodium bicarbonate, calcium chloride and cacodylate). All techniques involve the use of ammonium sulphate fractionation and centrifugation to precipitate the enzyme. Collagenases are normally purified using chromatographic techniques such as gel-filtration, ion-exchange and affinity column chromatography. Collagenase can be assayed with a number of methods, including: colorimetric absorbance, viscometry, radioactivity and fluorescence spectroscopy. Collagenases are partly responsible for toughness in red meats and are used as tenderizers in food industry, have application in the fur and hide tanning to ensure uniform dying of leather, used in medicine to treat burns and ulcers, eliminate scar tissues, transplantation of organs. Conclusion: Understanding of the nature of the enzymes and identifying the most suitable resources and the methods for their extraction and purification will have significant impact on the fish processing, food and medical industries.

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“…The test tube experiments that have been performed so far showed that it is difficult to achieve complete degradation of adult lamellar bone with a single bone proteinase (9,10). On the other hand, various biological approaches have shown that both MMPs and cysteine proteinases participate in the bone resorption processes (8,(11)(12)(13). Representatives of these two types of proteinases were identified in osteoclasts, the cells responsible for bone resorption.…”

mentioning

confidence: 99%

The Collagenolytic Activity of Cathepsin K Is Unique among Mammalian Proteinases

Garnero¹,

Borel²,

Byrjalsen³

et al. 1998

Journal of Biological Chemistry

575

445

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Type I collagen fibers account for 90% of the organic matrix of bone. The degradation of this collagen is a major event during bone resorption, but its mechanism is unknown. A series of data obtained in biological models strongly suggests that the recently discovered cysteine proteinase cathepsin K plays a key role in bone resorption. Little is known, however, about the actual action of cathepsin K on type I collagen. Here, we show that the activity of cathepsin K alone is sufficient to dissolve completely insoluble collagen of adult human cortical bone. We found that the collagenolytic activity of cathepsin K is directed both outside the helical region of the molecule, i.e. the typical activity of cysteine proteinases, and at various sites inside the helical region, hitherto believed to resist all mammalian proteinases but the collagenases of the matrix metalloproteinase family and the neutrophil elastase. This property of cathepsin K is unique among mammalian proteinases and is reminiscent of bacterial collagenases. It is likely to be responsible for the key role of cathepsin K in bone resorption.The only mammalian proteinases that have been shown to attack the native triple helical region of type I collagen are the collagenases of the MMP 1 family (1-3) and the neutrophil serine elastase (4) They cleave the type I collagen triple helix across all three chains (i.e. two ␣1 chains and one ␣2 chain) only at a specific point three-quarters of the way to the Nterminal end of the collagen molecule. Proteinases with broad specificity, such as cysteine proteinases, attack only the extrahelical regions that are located at either end of native collagen (telopeptides) and that represent only 4% of the molecule (5). Because the telopeptides are involved in intra-and intermolecular links, this attack may separate individual molecules. The latter proteinases may also attack destabilized triple helices, acting thereby as gelatinases. At 37°C, such a destabilization may transiently affect a small proportion of collagen molecules, because the melting temperature of soluble collagen is only a few degrees higher. It has also been emphasized that when collagen molecules are cross-linked and arranged in insoluble fibers they become more resistant to proteolysis (6). However, the co-operation of proteinases with distinct specificities toward the chemical bonds of collagen fibers has been shown to favor the efficiency of collagenolysis (7).Insoluble type I collagen fibers constitute 90% of the organic matrix of bone, and their degradation is necessary for bone resorption (8). The test tube experiments that have been performed so far showed that it is difficult to achieve complete degradation of adult lamellar bone with a single bone proteinase (9, 10). On the other hand, various biological approaches have shown that both MMPs and cysteine proteinases participate in the bone resorption processes (8,(11)(12)(13). Representatives of these two types of proteinases were identified in osteoclasts, the cells responsible for bone resorptio...

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A new synthetic inhibitor of mammalian tissue collagenase inhibits bone resorption in culture

Cited by 94 publications

References 28 publications

Initiation of Osteoclast Bone Resorption by Interstitial Collagenase

Initiation of Osteoclast Bone Resorption by Interstitial Collagenase

Extraction and Purification of Collagenase Enzymes: A Critical Review

The Collagenolytic Activity of Cathepsin K Is Unique among Mammalian Proteinases

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