Lysine hydroxylation of type I collagen telopeptides varies from tissue to tissue, and these distinct hydroxylation patterns modulate collagen cross-linking to generate a unique extracellular matrix. Abnormalities in these patterns contribute to pathologies that include osteogenesis imperfecta (OI), fibrosis, and cancer. Telopeptide procollagen modifications are carried out by lysyl hydroxylase 2 (LH2); however, little is known regarding how this enzyme regulates hydroxylation patterns. We identified an ER complex of resident chaperones that includes HSP47, FKBP65, and BiP regulating the activity of LH2. Our findings show that FKBP65 and HSP47 modulate the activity of LH2 to either favor or repress its activity. BiP was also identified as a member of the complex, playing a role in enhancing the formation of the complex. This newly identified ER chaperone complex contributes to our understanding of how LH2 regulates lysyl hydroxylation of type I collagen C-telopeptides to affect the quality of connective tissues. © 2017 American Society for Bone and Mineral Research.
- MeSH
- biologické modely MeSH
- buněčné linie MeSH
- chaperon endoplazmatického retikula BiP MeSH
- hmotnostní spektrometrie MeSH
- hydroxylace MeSH
- kolagen typu I metabolismus MeSH
- lidé MeSH
- lysin metabolismus MeSH
- lysinhydroxylasa metabolismus MeSH
- multiproteinové komplexy metabolismus MeSH
- mutace genetika MeSH
- myši MeSH
- peptidy metabolismus MeSH
- povrchová plasmonová rezonance MeSH
- prokolagen metabolismus MeSH
- proteiny tepelného šoku HSP47 metabolismus MeSH
- proteiny tepelného šoku metabolismus MeSH
- proteiny vázající takrolimus metabolismus MeSH
- stabilita enzymů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chaperon endoplazmatického retikula BiP MeSH
- collagen type I trimeric cross-linked peptide MeSH Prohlížeč
- FKBP10 protein, human MeSH Prohlížeč
- kolagen typu I MeSH
- lysin MeSH
- lysinhydroxylasa MeSH
- multiproteinové komplexy MeSH
- peptidy MeSH
- prokolagen MeSH
- proteiny tepelného šoku HSP47 MeSH
- proteiny tepelného šoku MeSH
- proteiny vázající takrolimus MeSH
- SERPINH1 protein, human MeSH Prohlížeč
Our goal was to determine if venlafaxine has a negative effect on bone metabolism. Rats were divided into three groups. The sham-operated control group (SHAM), the control group after orchidectomy (ORX), and the experimental group after orchidectomy received venlafaxine (VEN ORX) in standard laboratory diet (SLD) for 12 weeks. Bone mineral content (BMC) was measured by dual energy X-ray absorptiometry (DXA). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), amino-terminal propeptide of procollagen type I (P1NP), bone alkaline phosphatase (BALP), sclerostin and bone morphogenetic protein 2 (BMP-2) were examined in bone homogenate. The femurs were used for biomechanical testing. Compared to the ORX group we found lower BMD in the diaphysis area of the femur in the VEN ORX group, suggesting a preferential effect on cortical bone. Of the bone metabolism markers, there was significant decrease (ORX control group versus VEN ORX experimental group) in BALP levels and increase in sclerostin and CTX-I levels, suggesting a decrease in osteoid synthesis and increased bone resorption. The results suggest that the prolonged use of venlafaxine may have a negative effect on bone metabolism. Further studies are warranted to establish whether venlafaxine may have a clinically significant adverse effect on bone.
- Klíčová slova
- BALP, Bone mineral density, CTX-I, SNRI, Venlafaxine,
- MeSH
- absorpční fotometrie MeSH
- alkalická fosfatasa metabolismus MeSH
- bederní obratle diagnostické zobrazování účinky léků MeSH
- biologické markery metabolismus MeSH
- biomechanika MeSH
- femur diagnostické zobrazování účinky léků MeSH
- genetické markery MeSH
- inhibitory zpětného vychytávání serotoninu a noradrenalinu toxicita MeSH
- kolagen typu I metabolismus MeSH
- kosti a kostní tkáň účinky léků metabolismus účinky záření MeSH
- kostní denzita účinky léků MeSH
- kostní morfogenetické proteiny metabolismus MeSH
- kostní morfogenetický protein 2 metabolismus MeSH
- lidé MeSH
- orchiektomie * MeSH
- osteoprotegerin metabolismus MeSH
- peptidové fragmenty metabolismus MeSH
- peptidy metabolismus MeSH
- potkani Wistar MeSH
- prokolagen metabolismus MeSH
- remodelace kosti účinky léků MeSH
- tibie účinky léků metabolismus MeSH
- venlafaxin hydrochlorid toxicita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alkalická fosfatasa MeSH
- biologické markery MeSH
- Bmp2 protein, rat MeSH Prohlížeč
- collagen type I trimeric cross-linked peptide MeSH Prohlížeč
- genetické markery MeSH
- inhibitory zpětného vychytávání serotoninu a noradrenalinu MeSH
- kolagen typu I MeSH
- kostní morfogenetické proteiny MeSH
- kostní morfogenetický protein 2 MeSH
- osteoprotegerin MeSH
- peptidové fragmenty MeSH
- peptidy MeSH
- procollagen Type I N-terminal peptide MeSH Prohlížeč
- prokolagen MeSH
- Sost protein, rat MeSH Prohlížeč
- Tnfrsf11b protein, rat MeSH Prohlížeč
- venlafaxin hydrochlorid MeSH
AIMS: This study was designed to investigate the predictive value of serum collagen biomarkers on the outcomes of acute ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). METHODS: Two hundred and ten patients with STEMI were successfully treated with PCI within 6 hrs ofthe onset of chest pain. The levels of serum procollagen type I carboxyterminal peptide (PICP) and procollagen type III peptide (PIIINP) were measured by enzymelinked immunosorbent assay (ELISA) before, 3 and 6 months after PCI. Left ventricular ejection fraction was assessed by echocardiography at 3 and 6 months after PCI. The composite endpoints were death by any cause, recurrent myocardial infarction, heart failure or stroke. RESULTS: At the end of the 12-month follow up, 29 patients (13.8%) experienced an end point. The level of serum PICP in patients with an end point was higher than in patients without an end point 7 days (19.45 ± 2.17 vs 14.95 ± 3.07 ng/mL, P<0.05) or 3 month after the PCI (29.87 ± 3.02 vs 22.14 ± 3.33 ng/mL, P<0.05). The serum PIIINP level in patients with an end point was also higher than those without 7 days after PCI (59.34 ± 4.23 vs 48.78 ± 4.23 ng/mL, P<0.05). Multivariate logistic regression analysis showed day 7 (OR=2.170, 95% CI 1.583-4.345, P=0.01) and 3-month serum PICP (OR=2.340, 95% CI 1.431-4.650, P=0.01) were independent predictors of composite end points. CONCLUSIONS: Persistent elevation of serum collagen marker PICP three months after PCI predicts an adverse outcome for patients with acute ST-elevation myocardial infarction.
- Klíčová slova
- left ventricular function, myocardial infarction, percutaneous coronary intervention, procollagen type I carboxyterminal peptide,
- MeSH
- analýza rozptylu MeSH
- biologické markery metabolismus MeSH
- dysfunkce levé srdeční komory etiologie MeSH
- infarkt myokardu krev patofyziologie terapie MeSH
- koronární angioplastika * MeSH
- lidé středního věku MeSH
- lidé MeSH
- peptidové fragmenty metabolismus MeSH
- prokolagen metabolismus MeSH
- recidiva MeSH
- tepový objem fyziologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- peptidové fragmenty MeSH
- procollagen type I carboxy terminal peptide MeSH Prohlížeč
- procollagen Type III-N-terminal peptide MeSH Prohlížeč
- prokolagen MeSH
There is only limited data concerning the effect of the newer antiepileptic drugs on bone. The objective of this study was to determine the effect of topiramate (TPM) and lamotrigine (LTG) monotherapy on bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomized (ORX) rat model. 24 orchidectomized Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LTG or TPM for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density. The concentrations of bone metabolism markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Compared to the control group, both test groups had significantly lower weight, fat mass, whole body and femur BMD, BMC and reduced mechanical strength of bone. All of these changes were more pronounced in rats exposed to LTG. In conclusion, both LTG and TPM significantly reduce BMD and body weight and impair mechanical strength of bone. A question arises as to the degree of dependence of the effect on the dose. Further studies are warranted to establish whether LTG and TPM may have a clinically significant effect on BMD exclusively in the model of gonadectomized rats, or whether the effect applies also in the model of gonadally intact animals, and in the respective human models.
- Klíčová slova
- Antiepileptic drugs, Bone markers, Bone mineral density, Lamotrigine, Topiramate,
- MeSH
- absorpční fotometrie MeSH
- alkalická fosfatasa metabolismus MeSH
- antikonvulziva aplikace a dávkování MeSH
- aplikace orální MeSH
- biomechanika účinky léků MeSH
- ELISA MeSH
- fruktosa analogy a deriváty farmakologie MeSH
- kolagen typu I metabolismus MeSH
- kosti a kostní tkáň účinky léků metabolismus MeSH
- kostní denzita účinky léků MeSH
- kostní morfogenetický protein 2 metabolismus MeSH
- krysa rodu Rattus MeSH
- lamotrigin MeSH
- modely u zvířat MeSH
- neparametrická statistika MeSH
- orchiektomie MeSH
- osteoprotegerin krev MeSH
- peptidové fragmenty metabolismus MeSH
- peptidy metabolismus MeSH
- potkani Wistar MeSH
- prokolagen metabolismus MeSH
- složení těla účinky léků MeSH
- tělesná hmotnost účinky léků MeSH
- topiramat MeSH
- triaziny aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alkalická fosfatasa MeSH
- antikonvulziva MeSH
- collagen type I trimeric cross-linked peptide MeSH Prohlížeč
- fruktosa MeSH
- kolagen typu I MeSH
- kostní morfogenetický protein 2 MeSH
- lamotrigin MeSH
- osteoprotegerin MeSH
- peptidové fragmenty MeSH
- peptidy MeSH
- procollagen Type I N-terminal peptide MeSH Prohlížeč
- prokolagen MeSH
- topiramat MeSH
- triaziny MeSH
OBJECTIVE: Statins have been widely used for the treatment of hypercholesterolemia, and recent studies have shown that these drugs also affect bone metabolism. The aim of this experiment was to follow the effect of atorvastatin on bone metabolism in male albino Wistar rats. METHODS: Our study was carried out on 16 rats (240 +/- 10g) which were randomly divided into 2 groups of 8 animals. The control group (CO) was given aqua pro injectione (0.2 mL/100 g BW; gavage) and the experimental group atorvastatin suspension (AT; 0.3 mg in 0.2 mL aqua pro inj./100 g BW; gavage) daily for 8 weeks. We examined serum markers of bone turnover using ELISA - C-terminal crosslinking telopeptide of type I collagen (CTX-I), total osteocalcin (total OC), procollagen type I N propeptide (PINP) and bone alkaline phosphatase (bone ALP). We investigated bone morphogenetic protein-2 (BMP-2) in the proximal tibia using Western blot analysis. Additionally, we measured bone mineral density (BMD). The femurs were used for a three-point bending test and compression test of the femoral neck. RESULTS: After 8 weeks of atorvastatin administration, a significant decrease was found in serum level of bone ALP to 30% vs. CO (p = 0.005). PINP, CTX-I and OC did not change significantly. The expression of BMP-2 was increased. There were no significant differences in BMD measurements, three-point bending test or compression test of the femoral neck. CONCLUSIONS: Our results suggest that atorvastatin has a positive effect on bone metabolism in rats by maintenance of BMD and the biomechanical characteristics of bone. Atorvastatin influenced bone metabolism by decreasing bone ALP, and probably in consequence increasing expression of BMP-2 in rats.
- MeSH
- absorpční fotometrie MeSH
- alkalická fosfatasa metabolismus MeSH
- atorvastatin MeSH
- biologické markery MeSH
- biomechanika MeSH
- elektroforéza v polyakrylamidovém gelu MeSH
- kolagen typu I metabolismus MeSH
- kosti a kostní tkáň účinky léků metabolismus MeSH
- kostní denzita účinky léků MeSH
- kostní morfogenetický protein 2 metabolismus MeSH
- krysa rodu Rattus MeSH
- kyseliny heptylové farmakologie MeSH
- osteokalcin metabolismus MeSH
- osteoprotegerin metabolismus MeSH
- peptidové fragmenty metabolismus MeSH
- potkani Wistar MeSH
- prenylace proteinů MeSH
- prokolagen metabolismus MeSH
- pyrroly farmakologie MeSH
- statiny farmakologie MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alkalická fosfatasa MeSH
- atorvastatin MeSH
- biologické markery MeSH
- kolagen typu I MeSH
- kostní morfogenetický protein 2 MeSH
- kyseliny heptylové MeSH
- osteokalcin MeSH
- osteoprotegerin MeSH
- peptidové fragmenty MeSH
- procollagen Type I N-terminal peptide MeSH Prohlížeč
- prokolagen MeSH
- pyrroly MeSH
- statiny MeSH
OBJECTIVES: To analyze the predictive value of cardiac collagen metabolism "in vivo" in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI). DESIGN: Forty-five patients (age 66 +/- 8.27) underwent biochemical analysis for cardiac collagen metabolism (groups A, B and C); 30 patients with their first MI were treated with successful PCI (group A; n = 30), group B (n = 5) were MI patients with unsuccessful PCI. Group C were patients without MI (n = 10), they underwent elective diagnostic coronary angiography only. The collagen metabolism was analyzed in acute and subacute MI phases by using serum blood markers: the carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP) and carboxy-terminal telopeptide of type I collagen (ICTP). Furthermore, the ejection fraction (EF) and left ventricular end-diastolic volume maximal changes in the course of 6 months were measured by echocardiography. RESULTS: A significant increase of both PICP and PIIINP on day 4 following MI was detected. Furthermore, PICP and PIIINP level assessed on the 30th day was significantly higher in the PCI unsuccessful group versus successful group. PICP level on day 4 above 110 microg/l and PIIINP level above 4 microg/l was significantly often found in the subgroup of patients with the EF improvement less than 10% or worsening and with significant left ventricular dilatation during 6 months follow-up. Cardiac catheterization itself does not affect collagen metabolism. CONCLUSION: We concluded that collagen metabolism markers enable to study in vivo the MI healing and to predict left ventricular functional and volume changes.
- MeSH
- biologické markery krev metabolismus MeSH
- časové faktory MeSH
- echokardiografie MeSH
- funkce levé komory srdeční MeSH
- infarkt myokardu metabolismus MeSH
- kolagen typu I MeSH
- kolagen metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- peptidové fragmenty krev metabolismus MeSH
- peptidy MeSH
- prokolagen krev metabolismus MeSH
- remodelace komor fyziologie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- collagen type I trimeric cross-linked peptide MeSH Prohlížeč
- kolagen typu I MeSH
- kolagen MeSH
- peptidové fragmenty MeSH
- peptidy MeSH
- procollagen type I carboxy terminal peptide MeSH Prohlížeč
- procollagen Type III-N-terminal peptide MeSH Prohlížeč
- prokolagen MeSH
The aims of the present study were to analyze cardiac collagen metabolism changes in vivo during acute and nonacute phases of ST elevation myocardial infarction (STEMI) in patients who were treated with primary coronary intervention (PCI) only, and to determine the predictive significance of collagen I and III synthesis markers (PICP, PIIINP) as well as the collagen I degradation marker (ICTP) on left ventricular function and volume changes after STEMI. Serum levels of the carboxy-terminal propeptide of type I procollagen (PICP) and amino-terminal propeptide of type III procollagen (PIIINP) assessed on the 30th day and the carboxyterminal telopeptide located at the C end of collagen type I (ICTP) assessed on the 7th day after STEMI were significantly higher (P = 0.01, P = 0.019, P = 0.04, respectively) in the PCI unsuccessful group than in the PCI successful group. These findings support the theory that early and successful PCI not only limits the amount of muscle necrosis but also protects cardiac collagen from ischemia-related injury. PICP and PIIINP levels assessed on the fourth day after acute STEMI enables us to predict the development of left ventricular function (EF) and end-diastolic volume changes over the course of 6 months, irrespective of the initial EF or revascularization success.
- MeSH
- balónková koronární angioplastika * MeSH
- biologické markery metabolismus MeSH
- elektrokardiografie MeSH
- extracelulární matrix metabolismus MeSH
- funkce levé komory srdeční MeSH
- infarkt myokardu metabolismus patofyziologie terapie MeSH
- kolagen metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- myokard metabolismus MeSH
- peptidové fragmenty metabolismus MeSH
- prokolagen metabolismus MeSH
- remodelace komor * MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- kolagen MeSH
- peptidové fragmenty MeSH
- procollagen type I carboxy terminal peptide MeSH Prohlížeč
- procollagen Type III-N-terminal peptide MeSH Prohlížeč
- prokolagen MeSH
BACKGROUND: To study the levels of the aminoterminal propeptide of type III(PIIINP) and carboxyterminal propeptide of type I procollagen (PICP) in plasma and in the wall of abdominal aortic aneurysms in relation to their size and symptomatology. PIIINP serves as a marker of turnover and PICP as a marker of the synthesis of the corresponding collagens. EXPERIMENTAL DESIGN: A prospective non-randomised study. SETTING: University Hospital, Plzen, Czech Republic. PATIENTS: Eighty-six patients who underwent resection of abdominal aortic aneurysms, average age 70.1 years (range 45 to 91 years), men to women ratio 5:1. The indication for resection was its symptomatology without relation to its diameter, and diameter over 5 cm in asymptomatic patients. Twenty patients (with similar age and gender distribution) scheduled for hernia repair or laparoscopic cholecystectomy were examined as a control group. MAIN OUTCOME MEASURES: The plasma and tissue PICP and PIIINP concentrations were evaluated using radioimmunoassay methods. The plasma samples were taken from the cubital vein without the use of a tourniquet. Full-thickness sections of the anterior abdominal aortic aneurysm wall at the site of the largest aneurysm diameter were taken at the time of operation. RESULTS: A significant difference between plasma PIIINP levels in patients with abdominal aortic aneurysms and the control group was observed (p<0.01). No correlation of PICP, PIIINP plasma levels with diameter and symptomatology of abdominal aortic aneurysms was found. The increase in PHIIINP tissue concentration was significant in patients with increasing diameter and positive symptomatology (p<0.01). No statistically significant correlation between plasma and tissue PICP and PIIINP concentrations was observed. CONCLUSIONS: The metabolism of type III collagen is increased in patients with abdominal aortic aneurysm, in contrast to type I collagen. The result is a degradation of collagen in the aneurysmal wall. The turnover of type III collagen increases with the enlargement of the aneurysm diameter and with the positive symptomatology. Degradation of type III collagen in the aneurysmal wall has therefore a fundamental significance for abdominal aortic aneurysm rupture. Because no correlation between plasma and tissue levels of PIIINP was found, the plasma levels of PIIINP cannot be used as the plasma markers of this process.
- MeSH
- aneurysma břišní aorty metabolismus MeSH
- aorta abdominalis metabolismus MeSH
- biologické markery MeSH
- lidé středního věku MeSH
- lidé MeSH
- peptidové fragmenty krev metabolismus MeSH
- prokolagen krev metabolismus MeSH
- prospektivní studie MeSH
- radioimunoanalýza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- biologické markery MeSH
- peptidové fragmenty MeSH
- procollagen type I carboxy terminal peptide MeSH Prohlížeč
- procollagen Type III-N-terminal peptide MeSH Prohlížeč
- prokolagen MeSH
The authors investigated the intensity of collagen synthesis in patients subjected to operation or re-operation of a total endoprosthesis of the hip joint. The patients suffered from osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. The authors assessed the activity of collagen glucosyl transferase (S-GGT) and the concentration of the N-terminal propeptide procollagen type III by two methods (S-Pro III-N-P and S-Fab) in serum before and after operation. A significant rise of S-GGT and S-Fab, as compared with controls, occurred only after operation while S-Pro III-N-P was elevated already before operation. S-GGT did not differ before and after operation, while N-propeptide concentration rose when either method was used.
- MeSH
- dospělí MeSH
- glukosyltransferasy metabolismus MeSH
- kolagen biosyntéza MeSH
- krevní sedimentace MeSH
- kyčelní protézy * MeSH
- lidé středního věku MeSH
- lidé MeSH
- peptidové fragmenty metabolismus MeSH
- prokolagen metabolismus MeSH
- reoperace MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- glukosyltransferasy MeSH
- kolagen MeSH
- peptidové fragmenty MeSH
- procollagen Type III-N-terminal peptide MeSH Prohlížeč
- prokolagen MeSH
- UDP glucose-collagen glucosyltransferase MeSH Prohlížeč