Type XI collagen‐degrading activity in human osteoarthritic cartilage

Yu, Lucino P.; Smith, Gerald N.; Brandt, Kenneth D.; Capello, William N.

doi:10.1002/art.1780331104

Cited by 19 publications

(7 citation statements)

References 27 publications

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“…Enzymatic degradation of type XI collagen may be important in disease states. 23 Matrix metalloproteinase 2 (MMP2) degrades type XI collagen by recognising Gly-Iso or Gly-Leu bonds 24 ; however, Gly-Iso followed by Pro is resistant to collagenase. 25 Increased activity of MMP2 destroys collagen architecture.…”

Section: Hypothesised Effect Of the P621t Mutationmentioning

confidence: 99%

Mutation of COL11A2 causes autosomal recessive non-syndromic hearing loss at the DFNB53 locus

Chen

2005

Journal of Medical Genetics

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Background: Allele variants of COL11A2, encoding collagen type XI a2, cause autosomal dominant non-syndromic hearing loss (ARNSHL) at the DFNA13 locus (MIM 601868) and various syndromes that include a deafness phenotype. Objective: To describe a genome-wide scan carried out on a consanguineous Iranian family segregating ARNSHL. Results: Genotyping data identified a novel locus for ARNSHL on chromosome 6p21.3, which was designated DFNB53. Homozygosity for the P621T mutation of COL11A2 was present in all deaf persons in this family; this same variation was absent in 269 Iranian controls. Sequence comparison of collagen type XI a1 and a2 peptides across species shows that the replaced proline is an evolutionarily conserved amino acid. Conclusions: The P621T mutation of COL11A2 affects the Y position of the canonical -Gly-X-Y-repeat in collagens. It lies near the amino-terminus of the triple helical region and causes ARNSHL. This finding suggests that mutation type and location are critical determinants in defining the phenotype of COL11A2 associated diseases.

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Section: Hypothesised Effect Of the P621t Mutationmentioning

confidence: 99%

Mutation of COL11A2 causes autosomal recessive non-syndromic hearing loss at the DFNB53 locus

Chen

2005

Journal of Medical Genetics

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“…Matrix metalloproteinases (MMP) 1 pathological processes such as wound healing (1,2), skeletal growth and remodeling (3,4), cancer (5)(6)(7)(8)(9)(10), arthritis (11)(12)(13)(14), and periodontal disease (15,16).…”

Section: Introductionmentioning

confidence: 99%

Identification of Structural Elements Important for Matrix Metalloproteinase Type V Collagenolytic Activity as Revealed by Chimeric Enzymes

O’Farrell

Pourmotabbed

2000

Journal of Biological Chemistry

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Digestion of type V collagen by the gelatinases is an important step in tumor cell metastasis because this collagen maintains the integrity of the extracellular matrix that must be breached during this pathological process. However, the structural elements that provide the gelatinases with this unique proteolytic activity among matrix metalloproteinases had not been thoroughly defined. To identify these elements, we examined the substrate specificity of chimeric enzymes containing domains of gelatinase B and fibroblast collagenase. We have found that the addition of the fibronectin-like domain of gelatinase B to fibroblast collagenase is sufficient to endow the enzyme with the ability to cleave type V collagen. In addition, the substitution of the catalytic zinc-binding active site region of fibroblast collagenase with that of gelatinase B increased the catalytic efficiency of the enzyme 3- to 4-fold. This observation led to the identification of amino acid residues, Leu(397), Ala(406), Asp(410), and Pro(415), in this region of gelatinase B that are important for its efficient catalysis as determined by substituting these amino acids with the corresponding residues from fibroblast collagenase. Leu(397) and Ala(406) are important for the general proteolytic activity of the enzyme, whereas Asp(410) and Pro(415) specifically enhance its ability to cleave type V collagen and gelatin, respectively. These data provide fundamental information about the structural elements that distinguish the gelatinases from other matrix metalloproteinases in terms of substrate specificity and catalytic efficiency.

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“…Osteoarthritic cartilage however has revealed gelatinase activity in extracts. 15 The two major bands of gelatinolytic activity in the bone extracts most likely correspond to the two genetically distinct gelatinases that have been described: the 72-kDa and 92-kDa gelatinases.17-20 The 72-kDa gelatinase (MMP-2) is diminished to 66-kDa after autoactivation.17 This enzyme is found in culture media of normal connective tissue cells such as synovial and tendon fibroblasts,lg liver lipocytes,l9 bone cells2 and also in the culture media of malignant and transformed cell lines. The larger gelatinase has a molecular weight of 92-kDa in the proenzyme form which is reduced to 90-kDa after autoactivation.20 This gelatinase is predominantly found in cell culture media of neutrophils,21 macrophages,22.23 and polymorphonuclear leucocytes.…”

Section: Discussionmentioning

confidence: 97%

Direct extraction of gelatinases from rat bone

Bollen

Eyre

1993

Connective Tissue Research

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Many studies have shown that gelatinases are secreted into the medium of cultures of various cell and tissue types, including bone cells. It is not clear, however, to what extent the culture process is responsible for inducing the expression of these proteases. In the present study, gelatinolytic enzymes were extracted directly from bone and other tissues and identified as bands of activity on SDS-PAGE enzymograms using gelatin as the substrate. Two forms of gelatinase (72-kDa and 92-kDa) were present in extracts of normal young rat bone. Yields were markedly higher from compact bone than from other tissues (blood, marrow, tendon, cancellous bone, articular cartilage, and skin). More 92-kDa than 72-kDa gelatinase was extracted from bone. The proteolytic specificity of the 92-kDa gelatinase isolated from the bone extract was shown to be similar to that reported for the enzyme isolated from tissue culture media. Native type I collagen was not cleaved but heat denatured type I collagen (gelatin) and native type IV, type V, type IX and type XI collagens were degraded. The proteolytic activity was inhibited by EDTA. The results indicate that more gelatinases can be extracted from bone tissue than from other tissues using mild extraction conditions. The cellular origin and function of these enzymes in bone remain to be defined.

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Type XI collagen‐degrading activity in human osteoarthritic cartilage

Cited by 19 publications

References 27 publications

Mutation of COL11A2 causes autosomal recessive non-syndromic hearing loss at the DFNB53 locus

Mutation of COL11A2 causes autosomal recessive non-syndromic hearing loss at the DFNB53 locus

Identification of Structural Elements Important for Matrix Metalloproteinase Type V Collagenolytic Activity as Revealed by Chimeric Enzymes

Direct extraction of gelatinases from rat bone

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