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Biomedical subjects

D R Eyre

Publications and source records attributed to D R Eyre.

At least 73 records · Page 4Linked to original sources
PubMed1993

Structural analysis of the extension peptides on matrix forms of type V collagen in fetal calf bone and skin.

The structure of the extension peptides retained on the tissue form of type V collagen molecules was determined. Type V collagen alpha chains containing extension peptides were extracted from fetal calf skin and bone by 4 M guanidine-HCl and 0.5 M acetic acid, respectively. Collagens present in both extracts were fractionated by sodium chloride precipitation. The collagen alpha(V) chains were then resolved by reverse-phase high performance liquid chromatography. The N-terminal extension peptides were characterized by direct sequence analysis after deblocking with pyroglutamate amino-peptidase and analysis of the products of digestion by bacterial collagenase, chymotrypsin, V8 protease and endoproteinase Lys-C. The results showed that the retained extension peptides on type V collagen molecules in the extracellular matrix of skin and bone were amino-propeptides and that the alpha 2(V) chain retains an intact amino-propeptide while the alpha 1(V) chain appears to be partially processed. The extended alpha 1(V) chain isolated from fetal calf bone gave an identical amino-terminal sequence to that of the alpha 1(V) chain isolated from fetal calf skin, suggesting that a specific enzyme may be involved in processing the alpha 1(V) amino-propeptide.

Amino Acid Sequence↗
PubMed1993

Collagen crosslinks and mineral crystallinity in bone of patients with osteogenesis imperfecta.

In cortical bone samples from patients with osteogenesis imperfecta (OI), the concentrations of hydroxypyridinium cross-linking amino acids in collagen were measured by reversed-phase HPLC and the x-axis crystallinity of the apatite mineral phase was determined by x-ray diffraction. Bone samples from three patients with type I, nine patients with type III, and eight patients with type IV OI were analyzed and compared with human bone from nine controls. The concentration of the two chemical forms of the mature collagen crosslinking amino acids, hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), and the ratio HP/LP were found to be alike in bone collagen of OI patients and healthy controls. However, the c-axis crystallinity of the apatite was found to be reduced in the type III and IV OI patients compared with controls. Regression analysis of crosslink concentrations and c-axis crystallinity in OI bones did not show any correlation. Therefore, collagen molecules deposited in the extracellular matrix of OI bone appear to fulfill the structural requirements for the action of the enzyme lysyl oxidase, such that a normal concentration of intermolecular crosslinks is formed compared with healthy bone. Consequently, crosslink formation and apatite crystal growth seem to be regulated independently in OI bone.

Adolescent↗
PubMed1993

Post-translational control of collagen fibrillogenesis in mineralizing cultures of chick osteoblasts.

Cultured osteoblasts from chick embryo calvaria were used as a model system to investigate the post-translational extracellular mechanisms controlling the macroassembly of collagen fibrils. The results of these studies demonstrated that cultured osteoblasts secreted a collagenous extracellular matrix that assembled and mineralized in a defined temporal and spatial sequence. The assembly of collagen occurred in a polarized fashion, such that successive orthogonal arrays of fibrils formed between successive cell layers proceeding from the culture surface toward the media. Mineralization followed in the same manner, being observed first in the deepest and oldest fibril layers. Collagen fibrillogenesis, the kinetics of cross-link formation, and collagen stability in the extracellular matrix of the cultures were examined over a 30 day culture period. Between days 8 and 12 in culture, collagen fibril diameters increased from < 30 nm to an average of 30-45 nm. Thereafter, diameters ranged in size from 20 to 200 nm. Quantitation of the collagen cross-linking residues, hydroxylysyl pyridinoline (HP) and lysyl pyridinoline (LP), showed that these mature cross-links increased from undetectable levels to concentrations found in normal chick bone. Analysis of the kinetics of their formation by pulse-chase labeling the cultures with [3H]lysine showed a doubling time of approximately 5 days. The relationships between cross-link formation, fibrillogenesis, and collagen stability were examined in cultures treated with beta-aminopropionitrile (beta-APN), a potent inhibitor of lysyl oxidase and cross-link formation. In beta-APN-treated cultures, total collagen synthesis was increased twofold, with no change in mRNA levels for type I collagen, whereas the amount of collagen accumulated in the cell layer was decreased by 50% and mineral deposition was reduced. The rate of collagen retention in the matrix was assessed by pulse-chase analysis of [3H]proline over a 16 day period in control and beta-APN-treated cultures. In control cultures, about 20% of the labeled collagen was lost from the cell layers over a 16 day period compared with > 80% in the presence of beta-APN. The beta-APN-treated cultures also showed a wider diversity of fibril diameters with a median in the > 45-60 nm range. In summary, these data suggest that cross-linking and assembly of collagen fibrils secreted by osteoblasts in vitro occur in a fashion similar to that found in vivo. The rate of cross-link formation is relatively constant and may be correlated with increasing collagen mass.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminopropionitrile↗
PubMed1993

Viscoelastic shear properties of articular cartilage and the effects of glycosidase treatments.

The objectives of this study were to determine the viscoelastic shear properties of articular cartilage and to investigate the effects of the alteration of proteoglycan structure on these shear properties. Glycosidase treatments (chondroitinase ABC and Streptomyces hyaluronidase) were used to alter the proteoglycan structure and content of the tissue. The dynamic viscoelastic shear properties of control and treated tissues were measured and statistically compared. Specifically, cylindrical bovine cartilage specimens were subjected to oscillatory shear deformation of small amplitude (gamma degrees = 0.001 radian) over a physiological range of frequencies (0.01-20 Hz) and at various compressive strains (5, 9, 12, and 16%). The dynamic complex shear modulus was calculated from the measurements. The experimental results show that the solid matrix of normal articular cartilage exhibits intrinsic viscoelastic properties in shear over the range of frequencies tested. These viscoelastic shear properties were found to be dependent on compressive strains. Our data also provide significant insights into the structure-function relationships for articular cartilage. Significant correlations were found between the material properties (the magnitude of dynamic shear modulus, the phase shift angle, and the equilibrium compressive modulus), and the biochemical compositions of the cartilage (collagen, proteoglycan, and water contents). The shear modulus was greatly reduced when the proteoglycans were degraded by either chondroitinase ABC or Streptomyces hyaluronidase. The results suggest that the ability of collagen to resist tension elastically provides the stiffness of the cartilage matrix in shear and its elastic energy storage capability. Proteoglycans enmeshed in the collagen matrix inflate the collagen network and induce a tensile prestress in the collagen fibrils. This interaction of the collagen and proteoglycan within the cartilage matrix provides the complex mechanism that allows the tissue to resist shear deformation.

Animals↗
PubMed1993

The effect of short term treatment with alendronate on vertebral density and biochemical markers of bone remodeling in early postmenopausal women.

The effects of oral alendronate treatment on spinal bone mineral density and biochemical markers of bone turnover were assessed in women in the early postmenopausal period. Sixty-five women were treated with placebo or 5, 20, or 40 mg alendronate daily for 6 weeks in a double blind study. Treatment with alendronate decreased both urinary markers of bone resorption (pyridinolines, hydroxyproline, and calcium) and serum markers of bone formation (osteocalcin and alkaline phosphatase) in a dose-dependent fashion. This short term treatment with alendronate also produced a dose-dependent increase in lumbar bone mineral density measured 7.5 months after the completion of therapy. Median percent changes in integral spinal bone mineral density, as assessed by dual x-ray absorptiometry, were -2.3, -1.2, +0.7, and +1.2 after treatment with placebo and 5, 20, and 40 mg alendronate, respectively. Treatment with alendronate was well tolerated and produced no fever; gastrointestinal intolerance was no more common than with placebo treatment. Short term alendronate treatment in early postmenopausal women decreased bone turnover and increased vertebral density.

Adult↗
PubMed1993

Biochemical assessment of bone formation and resorption in acromegaly.

The effects of chronic GH and insulin-like growth factor-I (IGF-I) excess on bone metabolism were examined by measuring serum markers of bone formation and urine markers of bone resorption as well as vertebral bone densities in patients with active acromegaly. Fasting serum GH levels were elevated in all 27 patients (31 +/- 11 micrograms/L). Serum calcium levels were within the normal range, except in 3 of 27 (10%) patients with mild hypercalcemia. Urinary calcium excretion, however, was increased in 6 (22%) patients despite mainly normal serum PTH and 1,25-dihydroxyvitamin D levels, suggesting a direct renal GH and/or IGF-I-mediated calciuric effect. Urinary hydroxyproline/creatinine excretion was increased in all except 1 patient and correlated with plasma IGF-I levels (r = 0.49; P < 0.02; n = 22). A more specific indicator of bone collagen turnover, urinary type I collagen cross-linked N-telopeptide, was elevated in all except 1 patient and correlated with serum GH (r = 0.47; P < 0.02), IGF-I (r = 0.60; P < 0.005), and urinary hydroxyproline/creatinine excretion (r = 0.62; P < 0.001). Serum bone Gla protein (osteocalcin), a specific marker of osteoblastic activity, was also increased in 50% of the patients and correlated with urinary N-telopeptide (r = 0.47; P < 0.02), but not with serum GH or IGF-I concentrations. Trabecular bone density, as determined by quantitative computerized tomography of the lumbar spine, was increased in only 1 patient; 13 others had subnormal bone density. The results suggest that in long-standing acromegaly, osteoblastic and osteoclastic activities are increased. Vertebral trabecular bone mass is usually reduced. Urinary collagen cross-links may serve as a more specific marker of bone resorption in acromegaly.

Acromegaly↗
PubMed1993

Direct extraction of gelatinases from rat bone.

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.

Animals↗
PubMed1992

Incorporation of type I collagen molecules that contain a mutant alpha 2(I) chain (Gly580-->Asp) into bone matrix in a lethal case of osteogenesis imperfecta.

To understand more directly the tissue defect in osteogenesis imperfecta (OI), bone matrix was analyzed from an infant with lethal OI (type II) of defined mutation (collagen alpha 2(I)Gly580-->Asp). Pepsin-solubilized alpha 1(I) and alpha 2(I) chains and derived CNBr-peptides migrated more slowly on sodium dodecyl sulfate-polyacrylamide gel electrophoresis compared with normal human controls. The peptide alpha 2(I)CB3,5, predicted to contain the mutation site, ran as a retarded doublet band and was purified by high performance liquid chromatography and digested with V8 protease. Two peptides with amino-terminal sequences beginning at residue 576 of the alpha 2(I) chain were isolated. One had the normal sequence. The other differed in that aspartic acid replaced glycine at residue 580 as predicted from cDNA analysis, and in having an unhydroxylated proline at residue 579. From yields on microsequencing and the relative intensities of the two forms of alpha 2(I)CB3,5 on SDS-polyacrylamide gel electrophoresis, the ratio of mutant to normal alpha 2(I) chains in the infant's bone matrix was 0.7/1. Although the effects of an efficient incorporation of mutant chains on the properties of the bone matrix are unknown, it may be that in this OI case the tissue abnormalities result more from the presence of mutant protein than from an underexpression of matrix.

Amino Acid Sequence↗
PubMed1992

Identification of cross-linking sites in bovine cartilage type IX collagen reveals an antiparallel type II-type IX molecular relationship and type IX to type IX bonding.

Type IX collagen functions in covalent cross-linkage to type II collagen in cartilage (Eyre, D. R., Apone, S., Wu, J. J., Ericsson, L. H., and Walsh, K. A. (1987) FEBS Lett. 220, 337-341). To understand this molecular relationship better, an analysis of all cross-linking sites labeled by [3H]borohydride was undertaken using the protein prepared from fetal bovine cartilage. Sequence analysis of tryptic peptides containing the 3H-labeled cross-links showed that each of the chains of type IX collagen, alpha 1(IX), alpha 2(IX), and alpha 3(IX), contained a site of cross-linking at the amino terminus of the COL2 triple-helix to which the alpha 1(II)N-telopeptide could bond. The alpha 3(IX)COL2 domain alone also had an attachment site for the alpha 1(II)C-telopeptide. The distance between the alpha 1(II)N-telopeptide and alpha 1(II)C-telopeptide interaction sites, 137 residues, is equal to the length of the hole zone (0.6D) in a type II collagen fibril. This implies an antiparallel type II to type IX cross-linking relationship. Peptide analysis also revealed an unknown amino acid sequence linked to the COL2 cross-linking domains in both the alpha 1(IX) and alpha 3(IX) chains. Using antibodies to this novel peptide, its origin in the collagen alpha 3(IX)NC1 domain was established. In summary, the results confirm extensive covalent cross-linking between type IX and type II collagen molecules and reveal the existence of type IX-type IX bonding. These data provide a molecular basis for the proposed function of type IX collagen as a critical contributor to the mechanical stability and resistance to swelling of the collagen type II fibril framework of cartilage.

Amino Acid Sequence↗
PubMed1992

An amino acid substitution (Gly853-->Glu) in the collagen alpha 1(II) chain produces hypochondrogenesis.

The spondyloepiphyseal dysplasia subclassification of bone dysplasias includes achondrogenesis, hypochondrogenesis, and spondyloepiphyseal dysplasia congenita. The phenotypic expression of these disorders ranges from mild to perinatal lethal forms. We report the detection and partial characterization of a defect in type II collagen in a perinatal lethal form of hypochondrogenesis. Electrophoresis in sodium dodecyl sulfate-polyacrylamide of CB peptides (where CB represents cyanogen bromide) from type II collagen of the diseased cartilage showed a doublet band for peptide alpha 1(II)CB10 and evidence for post-translational overmodification of the major peptides (CB8, CB10, and CB11) seen as a retarded electrophoretic mobility. Peptide CB10 was digested by endoproteinase Asp-N; and on reverse-phase high pressure liquid chromatography, fragments of abnormal mobility were noted. Sequence analysis of a unique peptide D12 revealed a single amino acid substitution (Gly-->Glu) at position 853 of the triple helical domain. This was confirmed by sequence analysis of amplified COL2A1 cDNA, which revealed a single nucleotide substitution (GGA-->GAA) in 5 of 10 clones. Electron micrographs of the diseased cartilage showed a sparse extracellular matrix and chondrocytes containing dilated rough endoplasmic reticulum, which suggested impaired assembly and secretion of the mutant protein. This case further documents the molecular basis of the spondyloepiphyseal dysplasia spectrum of chondrodysplasias as mutations in COL2A1.

Amino Acid Sequence↗
PubMed1992

Cloning and developmental expression of the alpha 3 chain of chicken type IX collagen.

Fibrous and nonfibrous collagens comprise two major groups within the collagen family and both groups are found in a diverse variety of tissue fabrics. Type IX collagen is in the nonfibrous group; three different subunits of type IX collagen have been identified and the alpha 1 and alpha 2 subunits have been cloned. Using molecular cloning methods we have isolated, from an embryonic chicken cartilage library, cDNA clones which code for the entire alpha 3 chain of chicken type IX collagen. The cDNA clones encompass 2416 base pairs which have a conceptual open reading frame for a protein containing 675 amino acids including 193 Gly-X-Y repeats. These collagen repeats are in three separate domains which are interspersed with four major noncollagen domains. The collagen repeats also have four minor interruptions. This chain organization directly aligns with both the alpha 1 and alpha 2 chains of chicken type IX collagen. Comparison of the deduced amino acid sequence with peptide sequences of type IX collagens shows identity with 95 of the 96 known residues of the chicken alpha 3 chain and 81 of the 98 known residues of the bovine alpha 3 chain. The identical residues match those in five peptide fragments, two from the bovine protein and three from the chicken protein. The chicken and bovine alpha 3 chains have conserved cross-linking sites, separated by 137 residues which span 40 nm, the length of the hole zone in a collagen fibril. The NC3 domain of the chicken alpha 3 chain contains a repeat Cys-Pro motif which is present in both vertebrate and invertebrate nonfibrillar collagens. Northern blot hybridization exhibits a major mRNA of about 3.3 kilobases; this transcript is found in cartilaginous tissues in the embryo, including the developing limb and is not detected in other tissues or in the precondensation stage of limb development. The composite data delineate the primary structure of the alpha 3 chain of chicken type IX collagen, show its close relationship to the alpha 1 and alpha 2 chains, demonstrate its mRNA transcript, and show the appearance of that transcript in tissues of the developing chick embryo.

Amino Acid Sequence↗
PubMed1992

A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telopeptides in urine.

Peptides of low molecular weight that contain pyridinoline cross-links were isolated from adolescent human urine. A fraction was selected that was enriched in the N-telopeptide-to-helix intermolecular cross-linking domain of bone type I collagen. Mouse monoclonal antibodies were generated against these urinary peptides conjugated to a carrier protein as immunogen. A high-affinity antibody was identified that specifically bound to the trivalent peptides derived from the N-telopeptide-to-helix pyridinoline cross-linking site in type I collagen of human bone. This was confirmed by the direct isolation from human bone collagen of similar fragments recognized selectively by the antibody. A sensitive inhibition ELISA was established on microtiter plates that could quantify the bone-derived peptides in human urine. The assay, which can be run directly on untreated urine, was thoroughly tested against samples from normal subjects and from patients with metabolic bone disease. For example, strong correlations with urinary hydroxyproline and total pyridinoline cross-links were found in patients with Paget's disease of bone. The method shows considerable promise as a rapid and specific index of human bone resorption rates, with greatly improved specificity and convenience over total pyridinoline analysis. Potential applications include the study of normal metabolism, the diagnosis and monitoring of bone disease, and evaluating the effectiveness of antiresorption therapies.

Adolescent↗
PubMed1991

Isolation of a murine osteoclast colony-stimulating factor.

Cultures of a cell line derived from a murine mammary carcinoma that induces hypercalcemia were examined for soluble products that could induce osteoclasts to differentiate from murine bone marrow cells. The serum-free culture supernatant of this cell line stimulated growth of colonies from bone marrow cells that exhibited tartrate-resistant acid phosphatase (TRAPase) activity. These TRAPase-positive cells demonstrated essential features of osteoclasts when cultured with mineralized bone or dentin. The culture period required for colony development and the frequency of colony-forming cells indicated that relatively primitive marrow progenitors were stimulated by a tumor-derived factor(s) to form immature osteoclasts. Other colony-stimulating factors (CSFs), including granulocyte CSF, macrophage CSF, granulocyte-macrophage CSF and interleukin 3, were ruled out as the source of the activity produced by the tumor cells. The biological activity was successfully purified by gel filtration chromatography and reverse-phase HPLC. By SDS/PAGE, the activity was traced to a protein of approximately 17 kDa. Functional and biochemical studies of the purified factor suggest that it is distinct from any known CSF of myeloid cells. This protein appears to be a CSF for the osteoclast lineage, osteoclast CSF (O-CSF).

Acid Phosphatase↗
PubMed1991

Collagen in the ageing human intervertebral disc: an increase in covalently bound fluorophores and chromophores.

Human disc tissue gradually changes in colour from white in the young to yellow brown in the elderly. It was investigated to what degree this colouration and an associated fluorescence (which are characteristic of the non-enzymic reaction products of sugars or oxidized lipids with proteins), were the result of covalent derivatives on the collagen and other extracellular matrix proteins. Annulus fibrosus was obtained from four subjects aged 19 to 92 years. Papain-solubilized samples of tissue showed increasing yellow colour and the glycation-related fluorescence with age. On chromatography of CNBr-digests of tissue, the yellow colour and fluorescence remained bound to the CNBr-peptide fragments of the collagen and other matrix proteins. One peptide, alpha 1(II)CB12 (from type II collagen), was selected for purification and shown to contain increasing amounts of the characteristic fluorescence with age. Sequencing by Edman degradation over 24 cycles confirmed the identity of the peptide, and by analysis of a portion of the PTH-derivatives showed fluorescence at cycle 11, a lysine residue. The results imply that much of the yellow colour and characteristic fluorescence that accumulate in ageing human discs are contributed by covalent adducts (possibly derived from non-enzymic reactions with carbohydrates or lipids) linked to the collagen and probably to other long-lived matrix proteins. The disc is perhaps particularly susceptible to such protein modifications because, being large and avascular, of its tendency to a low oxygen tension. Such modifications to structural proteins may contribute to the commonly observed degeneration and impaired material function of ageing disc tissue.

Adult↗
PubMed1991

Sites of stromelysin cleavage in collagen types II, IX, X, and XI of cartilage.

Human recombinant stromelysin-1 was shown to cleave four types of collagen (types II, IX, X, and XI) prepared from bovine and rat cartilages at specific sites. Stromelysin-1 cleaved salt-soluble native molecules of type IX collagen into two main triple-helical fragments, COL1 and COL2,3. Protein microsequencing identified the exact cleavage sites in the NC2 domain of all three chains, alpha 1(IX), alpha 2(IX), and alpha 3(IX). Stromelysin-1 also acted as a "telopeptidase," in that it efficiently clipped intact molecules of types II and XI collagens at sites just inside their terminal cross-linking hydroxylysine residues. Native molecules of type X collagen were cleaved by stromelysin-1 within their triple helical domains at a COOH-terminal site that reduced the alpha 1(X) chain size by 10 kDa. These findings suggest an important role for stromelysin in the turnover and remodeling of the collagenous matrix of cartilage both normally and in degenerative joint disease.

Amino Acid Sequence↗
PubMed1991

The collagens of articular cartilage.

Articular cartilage contains at least five genetically distinct types of collagen. Types II, IX, and XI are cartilage-specific and are cross-linked together in a copolymeric network that forms the extracellular framework of the tissue. Fibrils of type II collagen provide the basic architecture. Type XI, a quantitatively minor fibril-forming collagen, is probably copolymerized with type II collagen in the matrix. Type IX collagen accounts for approximately 1% of the collagenous protein in adult articular cartilage and its molecules exist in the tissue covalently linked to the surface of type II collagen fibrils. Its suspected functions include regulating fibril diameters and mediating fibril-fibril and fibril-proteoglycan interactions. Stromelysin, a matrix metalloproteinase, was recently shown to degrade type IX collagen. This action may cause the collagen network swelling seen in articular cartilage in early experimental osteoarthritis, (OA). Collagen type X is restricted to the underlying calcified zone of articular cartilage, a zone that exhibits active remodeling in joints with OA. Degradation products of the various cartilage collagens show promise as molecular markers of joint disease.

Amino Acid Sequence↗
PubMed1991

Cartilage expression of a type II collagen mutation in an inherited form of osteoarthritis associated with a mild chondrodysplasia.

In a family who expressed severe dominantly inherited osteoarthritis, the underlying mutation was traced by genomic sequencing to a single base change which predicts an amino acid substitution of cysteine for arginine at residue 519 of the triple-helical domain of the type II collagen molecule (Ala-Kokko, L., C. T. Baldwin, R. W. Moskowitz, and D. J. Prockop. 1990. Proc. Natl. Acad. Sci. USA. 87:6565-6568). In the present study we examined whether this predicted protein phenotype was evident in articular cartilage obtained from an affected family member who underwent hip surgery. The cartilage collagen was solubilized by CNBr digestion. Cysteine residues were labeled by reduction and alkylation with 14C-iodoacetate. Collagen CNBr-peptides were fractionated by ion exchange and reverse phase column chromatography. One peptide from the alpha 1(II) chain, alpha 1(II) CB8, was found to be radiolabeled. Tryptic peptides were prepared from it and identified by microsequence analysis. The results show that approximately one-quarter of the alpha 1(II) chains present in the polymeric extracellular collagen of the patient's cartilage contained the Arg519-to-Cys substitution. The protein exhibited other abnormal properties including disulfide-bonded alpha 1(II)-dimers and signs of posttranslational overmodification. The premature cartilage failure and osteoarthritis are presumably a result of the abnormal type II collagen being expressed in the cartilage matrix.

Amino Acid Sequence↗