Collagen Synthesis and Degradation In Vivo. Evidence for Rapid Rates of Collagen Turnover with Extensive Degradation of Newly Synthesized Collagen in Tissues of the Adult Rat

McAnulty, Robin J.; Laurent, Geoffrey J.

doi:10.1016/s0174-173x(87)80001-8

Cited by 142 publications

(81 citation statements)

References 33 publications

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“…In the rat, the rate of turnover of collagen is 9 %\day in the heart, 4 %\day in the lung and less than 1 %\day in the dermis [14]. Collagen synthesis in rabbits occurs at a rate of 10 %\day in the lung, 3 %\day in skeletal muscle, 4 %\day in skin and 5 %\day in heart [15]. In humans, high turnover in arteries and heart has been reported in patients with hypertension and myocardial disease [3,16,17].…”

Section: Discussionmentioning

confidence: 99%

“…Urinary excretion of Pyr, DPyr and associated collagen type I C-telopeptide (CTx) or Ntelopeptide fragments are sensitive indices of the rate of bone resorption [13]. Some studies have investigated soft tissue collagen turnover in animals by the incorporation of radiolabelled proline into collagen and by measurement of the specific radioactivity of proline and hydroxyproline in body tissues [14,15]. Because these methods are invasive, few data are available in humans [3,[16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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Racemization and isomerization of type I collagen C-telopeptides in human bone and soft tissues: assessment of tissue turnover

Gineyts

Cloos²,

Borel

et al. 2000

Biochemical Journal

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Urinary excretion of the type I collagen C-telopeptide (CTx) has been shown to be a sensitive index of the rate of bone resorption. The human type I collagen sequence A"#!*HDGGR"#"% of CTx can undergo racemization of the aspartic acid residue Asp"#"" and isomerization of the bond between this residue and Gly"#"#. These spontaneous non-enzymic chemical reactions takes place in i o in bone, and the degree of racemization and isomerization of CTx molecules may be an index of the biological age and the remodelling of bone. The aim of the present study was to investigate the degree of racemization and isomerization of type I collagen in human connective soft tissues, in order to estimate the rate of collagen turnover in adult tissues and compare it with that of bone. We also performed a systematic evaluation of the pyridinium cross-link content in adult human tissues. Using antibodies raised against the different CTx forms, we found that INTRODUCTIONType I collagen, the major constituent of the extracellular matrix, is widely distributed in many tissues and organs, including bone, tendon, ligament and skin [1][2][3][4]. It is a heterotrimer [(α1) # α2] composed of a helicoidal domain with C-and N-telopeptides at either end. Recently it has been shown that the A"#!*HDGGR"#"% sequence of the C-telopeptide of the α1 chain of type I collagen can undergo isomerization and racemization [5,6]. These two processes, which are known to occur in several proteins in i o, are believed to derive from a spontaneous non-enzymic chemical reaction [7], and their end-products could represent a potential biochronological tool for investigating bone turnover in i o. For example, we showed previously that, in Paget 's disease of bone (characterized by a marked increase in bone turnover), the degree of isomerization is much lower than in adult normal bone [8]. However, at the present time it is not known if these processes are specific for bone tissue or can also occur in the extracellular matrix of soft tissues.The C-telopeptide of the α1 chain of type I collagen also contains a lysine residue which is involved in the formation of pyridinium cross-links in collagen. Pyridinoline (Pyr) and deoxypyridinoline (DPyr) are trifunctional cross-links which stabilize the structure of mature collagen fibres within the extracellular matrix. Pyr is mainly distributed in bone and cartilage, and to a lesser extent in collagen of other connective tissues, whereas DPyr is present mainly in bone and dentin [9][10][11][12]. Pyr and DPyrAbbreviations used : CTx, fragment derived from the C-telopeptide of the α1 chain of type I collagen containing the sequence AHDGGR ; αL, native peptide ; βL, isomerized peptide containing a β-Asp bond ; αD, native peptide containing a D-Asp residue ; βD, isomerized peptide containing a D-Asp residue ; Pyr, pyridinoline ; DPyr, deoxypyridinoline.1 To whom correspondence should be addressed (e-mail gineyts!lyon151.inserm.fr).bone and dermis are the tissues that show most racemization and isomerization. The type I collagen of ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Racemization and isomerization of type I collagen C-telopeptides in human bone and soft tissues: assessment of tissue turnover

Gineyts

Cloos²,

Borel

et al. 2000

Biochemical Journal

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“…In the lung, the ECM is subjected to a daily turnover of ,10% of total ECM, indicating that subtle changes in turnover rates accumulate to produce large changes in total ECM composition with time [10]. The ECM is largely composed of collagens, fibronectin, vitronectin, proteoglycans and glycosaminoglycans (GAGs) [11].…”

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confidence: 99%

Increased hyaluronic acid content in idiopathic pulmonary arterial hypertension

Papakonstantinou¹,

Kouri²,

Karakiulakis³

et al. 2008

European Respiratory Journal

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Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease characterised by elevated blood pressure in the pulmonary circulation. Initial vasoconstriction, proliferation of pulmonary arterial smooth muscle cells (PASMC) and increased deposition of extracellular matrix (ECM) contribute to pathological remodelling of pulmonary arterioles in IPAH. Glycosaminoglycans (GAGs), components of the ECM, control cellular proliferation and differentiation, but their expression in IPAH remains elusive.In the present study, GAG expression was investigated in the lungs of patients with IPAH or control transplant donors, and expression and localisation of GAG-metabolising enzymes were analysed in vivo and in vitro.A significant increase in the expression of hyaluronic acid (HA) was detected in IPAH lungs, associated with increased hyaluronan synthase (Has)1 and decreased hyaluronoglucosaminidase 1 gene expression, as assessed by quantitative RT-PCR and Western blotting. HAS1 protein localised to PASMC in vivo and increased HA deposition was observed in remodelled pulmonary arteries in IPAH. Transforming growth factor-b1, a profibrotic growth factor, led to increased HA secretion and HAS1 expression in primary PASMC.The results demonstrate an increased hyaluronic acid content in idiopathic pulmonary arterial hypertension lungs, associated with increased hyaluronan synthase 1 and decreased hyaluronoglucosaminidase 1 gene expression. Synergistic regulation of glycosaminoglycan-metabolising enzymes in favour of accumulation may, thus, regulate pathological vascular remodelling in idiopathic pulmonary arterial hypertension lungs.

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“…Under physiological conditions, synthesis and degradation of collagen is balanced to maintain tissue homeostasis [2,3]. In lung tissue, disrupted homeostasis leads to an imbalance between synthesis and degradation, resulting in either collagen destruction (i.e.…”

mentioning

confidence: 99%

“…In the lung, the collagen is subject to continuous remodelling and turnover [3] however, the intracellular pathway of collagen degradation is not seen under physiological conditions.…”

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confidence: 99%

Collagen phagocytosis by lung alveolar macrophages in animal models of emphysema

Lucattelli¹,

Cavarra²,

Santi³

et al. 2003

Eur Respir J

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Under steady state conditions the intracellular pathway is the major route of collagen catabolism in tissues characterised by rapid collagen turnover. In the lung, the collagen is subject to continuous remodelling and turnover however, the intracellular pathway of collagen degradation is unusual under physiological conditions. The current authors previously described crystalloid inclusions in alveolar macrophages of mice with genetic emphysema at the time of septal disruption. Using an immunogold technique these inclusions were identified as collagen-derived products and related to intracytoplasmic collagen degradation. To examine whether a different degree of protease burden in lung interstitium may influence the route of intracellular collagen degradation, collagen phagocytosis by alveolar macrophages was studied in various mouse models of emphysema at the time when emphysema develops.Evident collagen by-products in alveolar macrophages were observed in destructive processes characterising spontaneous models of emphysema either with negligible (blotchy mouse) or moderate (pallid mouse) elastase burden. On the other hand, intracellular collagen by-products were appreciated only in a few macrophages from tight-skin mice with high elastolytic burden and could not be observed in mice with a very severe burden after elastase instillation. In conclusion, the interstitial level of proteases burden can affect the way by which the collagen is cleared (intracellularly versus extracellularly). Eur Respir J 2003; 22: 728-734.

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Collagen Synthesis and Degradation In Vivo. Evidence for Rapid Rates of Collagen Turnover with Extensive Degradation of Newly Synthesized Collagen in Tissues of the Adult Rat

Cited by 142 publications

References 33 publications

Racemization and isomerization of type I collagen C-telopeptides in human bone and soft tissues: assessment of tissue turnover

Racemization and isomerization of type I collagen C-telopeptides in human bone and soft tissues: assessment of tissue turnover

Increased hyaluronic acid content in idiopathic pulmonary arterial hypertension

Collagen phagocytosis by lung alveolar macrophages in animal models of emphysema

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