Collagen metabolism in two types of autosomal dominant osteopetrosis during stimulation with thyroid hormones

1995 ◽  
Vol 133 (5) ◽  
pp. 557-563 ◽  
Author(s):  
Jens Bollerslev ◽  
Sian Thomas ◽  
Ellen Grodum ◽  
Kim Brixen ◽  
Ole Djøseland
Keyword(s):  
Thyroid Hormones ◽  
Type I Collagen ◽  
Autosomal Dominant ◽  
Collagen Metabolism ◽  
Significant Response ◽  
Type I ◽  
Type Ii ◽  
Creatinine Ratio ◽  
Carboxy Terminal ◽  
Autosomal Dominant Osteopetrosis

Bollerslev J, Thomas S, Grodum E, Brixen K, Djøseland 0. Collagen metabolism in two types of autosomal dominant osteopetrosis during stimulation with thyroid hormones. Eur J Endocrinol 1995;133:557–63. ISSN 0804–4643 In order to investigate collagen metabolism in two different types of autosomal dominant osteopetrosis (ADO), eight patients with type I (aged 23–61 years, mean 40.4 years) and nine patients with type II ADO (aged 20–49 years, mean 32.8 years) were compared with ten normal controls (aged 22–54 years, mean 35.4 years). The subjects were treated with 100 μg of triiodothyronine (T3) daily for 7 days and followed for a total of 4 weeks. Serum T3 increased in all subjects and a corresponding suppression of thyroid-stimulating hormone (TSH) was observed. Serum carboxy-terminal propeptide of type I collagen (S-PICP) in the control and type I groups showed no difference at baseline, whereas type II was lower than controls (p < 0.01). No significant alterations following stimulation were observed in any of the groups. Serum BGP (osteocalcin) values in the two patient groups were insignificantly lower than controls both at baseline and throughout the study. Following stimulation, a significant response was seen in the three groups (p < 0.001). The increases during the treatment period (delta values) for controls, type I and type II were 47.6% (p < 0.01), 51.7% (p = 0.05) and 34.8% (NS), respectively, with no difference between the groups. Serum bone-specific alkaline phosphatase (S-ALP) was not different between the groups and no alterations were observed in relation to treatment. The serum N-terminal propeptide of type III collagen (S-PIIINP) showed no difference at baseline between type I and controls but was significantly higher (p < 0.003) in type II than in the controls. After stimulation, significant responses were observed in all three groups (p < 0.001). Serum PIIINP increased following 1 week of treatment by 64% (p < 0.01), 41% (p < 0.02) and 18% (NS), respectively. Serum carboxy-terminal telopeptide of type I collagen (SICTP) did not differ between type I and controls at baseline but was increased in type II (p < 0.04), as it was throughout the observation period (p < 0.12 and p < 0.02). A significant response was observed in the three groups following stimulation. The delta values were 69% (p = 0.005), 56% (p < 0.02) and 34% (p < 0.02), respectively. The urinary hydroxyproline (OHP)/creatinine ratio did not differ between the groups either at baseline or following stimulation. A significant response (p < 0.001) was observed, with delta values of 44.2% (p < 0.06), 35.9% (p < 0.04) and 34.3% (p < 0.01), respectively. The two bone resorptive markers (S-ICTP and OHP/creatinine ratio) were correlated significantly at baseline for all three groups. It is concluded that collagen metabolism is disturbed in type II ADO, which might reflect an increased turnover of extra-osseous collagen. Because ICTP levels are increased in disorders with increased extra-osseous collagen turnover, we question the suitability of this parameter as a sensitive marker of bone resorption. Jens Bollerslev, Department of Medical Endocrinology, National University Hospital, N-0027 Oslo, Norway

scholarly journals Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach

2021 ◽  
Vol 22 (1) ◽  
pp. 429
Author(s):  
Luca Bini ◽  
Domitille Schvartz ◽  
Chiara Carnemolla ◽  
Roberta Besio ◽  
Nadia Garibaldi ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Type I ◽  
Tandem Mass ◽  
Type Ii ◽  
Type Iii ◽  
Bioinformatic Tools ◽  
Proteomic Approach ◽  
Fibrillin 1 ◽  
Heritable Disorder

Osteogenesis imperfecta (OI) is a heritable disorder that mainly affects the skeleton. The inheritance is mostly autosomal dominant and associated to mutations in one of the two genes, COL1A1 and COL1A2, encoding for the type I collagen α chains. According to more than 1500 described mutation sites and to outcome spanning from very mild cases to perinatal-lethality, OI is characterized by a wide genotype/phenotype heterogeneity. In order to identify common affected molecular-pathways and disease biomarkers in OI probands with different mutations and lethal or surviving phenotypes, primary fibroblasts from dominant OI patients, carrying COL1A1 or COL1A2 defects, were investigated by applying a Tandem Mass Tag labeling-Liquid Chromatography-Tandem Mass Spectrometry (TMT LC-MS/MS) proteomics approach and bioinformatic tools for comparative protein-abundance profiling. While no difference in α1 or α2 abundance was detected among lethal (type II) and not-lethal (type III) OI patients, 17 proteins, with key effects on matrix structure and organization, cell signaling, and cell and tissue development and differentiation, were significantly different between type II and type III OI patients. Among them, some non–collagenous extracellular matrix (ECM) proteins (e.g., decorin and fibrillin-1) and proteins modulating cytoskeleton (e.g., nestin and palladin) directly correlate to the severity of the disease. Their defective presence may define proband-failure in balancing aberrances related to mutant collagen.

Type VI collagen expression is upregulated in the early events of chondrocyte differentiation

Development ◽  
1993 ◽  
Vol 117 (1) ◽  
pp. 245-251
Author(s):  
R. Quarto ◽  
B. Dozin ◽  
P. Bonaldo ◽  
R. Cancedda ◽  
A. Colombatti
Keyword(s):  
Suspension Culture ◽  
Type I Collagen ◽  
Type Ii Collagen ◽  
Type I ◽  
Type Ii ◽  
Type Vi Collagen ◽  
Full Spectrum ◽  
Collagen Expression ◽  
Hypertrophic Chondrocyte

Dedifferentiated chondrocytes cultured adherent to the substratum proliferate and synthesize large amounts of type I collagen but when transferred to suspension culture they decrease proliferation, resume the chondrogenic phenotype and the synthesis of type II collagen, and continue their maturation to hypertrophic chondrocyte (Castagnola et al., 1986, J. Cell Biol. 102, 2310–2317). In this report, we describe the developmentally regulated expression of type VI collagen in vitro in differentiating avian chondrocytes. Type VI collagen mRNA is barely detectable in dedifferentiated chondrocytes as long as the attachment to the substratum is maintained, but increases very rapidly upon passage of the cells into suspension culture reaching a peak after 48 hours and declining after 5–6 days of suspension culture. The first evidence of a rise in the mRNA steady-state levels is obtained already at 6 hours for the alpha 3(VI) chain. Immunoprecipitation of metabolically labeled cells with type VI collagen antibodies reveals that the early mRNA rise is paralleled by an increased secretion of type VI collagen in cell media. Induction of type VI collagen is not the consequence of trypsin treatment of dedifferentiated cells since exposure to the actin-disrupting drug cytochalasin or detachment of the cells by mechanical procedures has similar effects. In 13-day-old chicken embryo tibiae, where the full spectrum of the chondrogenic differentiation process is represented, expression of type VI collagen is restricted to the articular cartilage where chondrocytes developmental stage is comparable to stage I (high levels of type II collagen expression).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Ιδιοπαθής υπερασβεστιουρία στην παιδική ηλικία

2017 ◽  
Author(s):  
Μαρία Παύλου
Keyword(s):  
Type I Collagen ◽  
Cross Linking ◽  
Type I ◽  
Nuclear Factor ◽  
Soluble Receptor ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Receptor Activator ◽  
Carboxy Terminal ◽  
Nuclear Factor Kb

Η ιδιοπαθής υπερασβεστιουρία (ΙΥΑ) στα παιδιά έχει επιπολασμό 2,2-17,7%. Ποσοστό 2635% των ασθενών εμφανίζει μειωμένη οστική πυκνότητα, που αποδίδεται μάλλον σε αυξημένη οστική απορρόφηση και/ή οστικό ανασχηματισμό, καθώς καταγράφεται φυσιολογική κατά μήκος αύξηση των οστών στα περισσότερα παιδιά με ΙΥΑ. Περιορισμένες είναι οι μελέτες εκτίμησης βιοχημικών δεικτών οστικού μεταβολισμού, αλλά και γονιδιακού ελέγχου σε παιδιά με ΙΥΑ στην διεθνή βιβλιογραφία και καμία στην ελληνική. Επίσης, δεν πραγματοποιήθηκαν μελέτες εκτίμησης των κυτταροκινών οστεοκλαστογένεσης οστεοπροτεγερίνη (osteoprotegerin, OPG) και sRANKL (soluble receptor activator of nuclear factor kB ligand) σε ασθενείς με ΙΥΑ. Σκοπός της μελέτης ήταν η εκτίμηση των βιοχημικών δεικτών οστικής παραγωγής, αλκαλική φωσφατάση (alkaline phosphatase, ALP) και οστεοκαλσίνη (osteocalcin, OC) και οστικής απορρόφησης β-Crosslaps (serum Carboxy-terminal cross-linking telopeptide of type I collagen) και της OPG και sRANKL στον ορό σε παιδιά με ΙΥΑ. Επίσης έγινε γονιδιακή ανάλυση των πολυμορφισμών του γονιδίου του ασβεστιοευαίσθητου υποδοχέα (Calcium sensing Receptor, CaSR). Πενήντα παιδιά με ΙΥΑ αποτέλεσαν την ομάδα ασθενών και 60 υγιή παιδιά την ομάδα ελέγχου. Οι ασθενείς εκτιμήθηκαν κατά τον χρόνο της διάγνωσης και 3 μήνες μετά την εφαρμογή διαιτητικών οδηγιών αντιμετώπισης της ΙΥΑ. Οι ασθενείς της μελέτης μας είχαν σχετικά ήπια προς μέτρια υπερασβεστιουρία (6,49±2,03 mg/Kg/day) κατά την ένταξη στην μελέτη. Μετά την εφαρμογή των διατροφικών οδηγιών, μείωσαν σημαντικά τα επίπεδα του Ca στα ούρα 24ώρου και τον λόγο του Ca προς κρεατινίνη στα δείγματα ούρων, χωρίς όμως να φτάνουν τις φυσιολογικές τιμές. Τα επίπεδα της ALP και OC και το ύψος των ασθενών δεν διέφεραν από της ομάδας ελέγχου, που δείχνει ανεπηρέαστη οστική παραγωγή στους ασθενείς. Τα επίπεδα των β-Crosslaps των ασθενών, στους δύο χρόνους εκτίμησης, ήταν υψηλότερα από των μαρτύρων, ενώ καταγράφηκε τάση μείωσης της μέσης τιμής μετά την τρίμηνη παρέμβαση. Το εύρημα δείχνει αυξημένη οστική απορρόφηση στους ασθενείς με τάση βελτίωσης κατά τον επανέλεγχο. Ο λόγος β-Crosslaps/OC στους ασθενείς κατά την ένταξη στην μελέτη ήταν αυξημένος συγκριτικά με των μαρτύρων, καταγράφοντας υψηλότερο ρυθμό οστικής απορρόφησης συγκριτικά με οστικής παραγωγής. Τα επίπεδα των OPG και sRANKL των ασθενών, στους δύο χρόνους εκτίμησης δε διέφεραν από των μαρτύρων. Ωστόσο, ο λόγος sRANKL/OPG στους ασθενείς κατά την ένταξη στην μελέτη ήταν ελαφρά χαμηλότερος, πιθανά σαν απάντηση αντιρρόπησης του υψηλότερου ρυθμού οστεοκλαστογένεσης. Από την γονιδιακή ανάλυση των πολυμορφισμών A986S, R990G και Q1011E του CaSR, καταγράφηκε συσχέτιση μόνο του A986S με την ΙΥΑ στα παιδιά της μελέτης. Συμπερασματικά οι ασθενείς της μελέτης μας φαίνεται να έχουν φυσιολογική οστική παραγωγή, αλλά αυξημένη οστική απορρόφηση, που βελτιώθηκε μετά την παρέμβαση. Βρέθηκε συσχέτιση μόνο του πολυμορφισμού A986S του CaSR με την ΙΥΑ. Θεωρούμε χρήσιμη την εκτίμηση των βιοχημικών δεικτών οστικής παραγωγής ALP και OC και απορρόφησης β-Crosslaps στον ορό στα παιδιά με ΙΥΑ, ως μια μη επεμβατική μέθοδο ανίχνευσης διαταραχών οστικού μεταβολισμού και παρακολούθησης της αντιμετώπισης της.

scholarly journals Role of collagenase in mediating in vitro alveolar epithelial wound repair

1999 ◽  
Vol 112 (2) ◽  
pp. 243-252
Author(s):  
E. Planus ◽  
S. Galiacy ◽  
M. Matthay ◽  
V. Laurent ◽  
J. Gavrilovic ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Epithelial Cell ◽  
Type I Collagen ◽  
Alveolar Epithelial Cell ◽  
Cell Monolayer ◽  
Type I ◽  
Type Ii ◽  
Alveolar Epithelial

Type II pneumocytes are essential for repair of the injured alveolar epithelium. The effect of two MMP collagenases, MMP-1 and MMP-13 on alveolar epithelial repair was studied in vitro. The A549 alveolar epithelial cell line and primary rat alveolar epithelial cell cultures were used. Cell adhesion and cell migration were measured with and without exogenous MMP-1. Wound healing of a cell monolayer of rat alveolar epithelial cell after a mechanical injury was evaluated by time lapse video analysis. Cell adhesion on type I collagen, as well as cytoskeleton stiffness, was decreased in the presence of exogenous collagenases. A similar decrease was observed when cell adhesion was tested on collagen that was first incubated with MMP-1 (versus control on intact collagen). Cell migration on type I collagen was promoted by collagenases. Wound healing of an alveolar epithelial cell monolayer was enhanced in the presence of exogenous collagenases. Our results suggest that collagenases could modulate the repair process by decreasing cell adhesion and cell stiffness, and by increasing cell migration on type I collagen. Collagen degradation could modify cell adhesion sites and collagen degradation peptides could induce alveolar type II pneumocyte migration. New insights regarding alveolar epithelial cell migration are particularly relevant to investigate early events during alveolar epithelial repair following lung injury.

scholarly journals Control of types I and II collagen and fibronectin gene expression in chondrocytes delineated by viral transformation.

1985 ◽  
Vol 5 (5) ◽  
pp. 1002-1008 ◽  
Author(s):  
E S Allebach ◽  
D Boettiger ◽  
M Pacifici ◽  
S L Adams
Keyword(s):  
Rous Sarcoma Virus ◽  
Type I Collagen ◽  
Skin Fibroblasts ◽  
Transcriptional Level ◽  
Type I ◽  
Type Ii ◽  
Intact Cells ◽  
Rous Sarcoma ◽  
Synthetic Rate ◽  
Sarcoma Virus

We have analyzed the effects of transformation by Rous sarcoma virus on expression of types I and II collagen and fibronectin genes in vertebral chondrocytes and compared them with expression of these genes in skin fibroblasts. Transformed chondrocytes display a dramatically decreased amount of type II collagen RNA, which can account fully for the decreased synthetic rate of this protein. Paradoxically, these cells also display greatly increased amounts of type I collagen RNAs, which are translated efficiently in vitro, but not in the intact cells. We show here that the type I collagen RNAs in transformed chondrocytes are nearly indistinguishable from those found in skin fibroblasts, and that they clearly differ from the type I collagen RNAs found in normal chondrocytes. Transformed chondrocytes also display an increased amount of fibronectin RNAs, which can account fully for the increased synthetic rate of this protein. Thus, the effects of transformation by Rous sarcoma virus on type I collagen and fibronectin RNAs in chondrocytes are the opposite of those observed in fibroblasts, which display decreased amounts of these three RNAs. These data indicate that the effects of transformation on the genes encoding type I collagen and fibronectin must be modulated by host cell-specific factors. They also imply that the types I and II collagen genes may be regulated by different mechanisms, the type I genes being controlled at both transcriptional and posttranscriptional levels, and the type II gene being controlled primarily at the transcriptional level.

scholarly journals Genetic Analysis of CLCN7 in an Old Female Patient with Type II Autosomal Dominant Osteopetrosis

2018 ◽  
Vol 33 (3) ◽  
pp. 380 ◽  
Author(s):  
Seon Young Kim ◽  
Younghak Lee ◽  
Yea Eun Kang ◽  
Ji Min Kim ◽  
Kyong Hye Joung ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Female Patient ◽  
Autosomal Dominant ◽  
Type Ii ◽  
Autosomal Dominant Osteopetrosis

Autosomal Dominant Osteopetrosis Type II

2009 ◽  
pp. 196-196
Author(s):  
Hubert Scharnagl ◽  
Winfried März ◽  
Markus Böhm ◽  
Thomas A. Luger ◽  
Federico Fracassi ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Type Ii ◽  
Autosomal Dominant Osteopetrosis

In situ hybridization reveals differential spatial distribution of mRNAs for type I and type II collagen in the chick limb bud

Development ◽  
1988 ◽  
Vol 103 (1) ◽  
pp. 111-118 ◽  
Author(s):  
C.J. Devlin ◽  
P.M. Brickell ◽  
E.R. Taylor ◽  
A. Hornbruch ◽  
R.K. Craig ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Limb Development ◽  
Type I Collagen ◽  
Type Ii Collagen ◽  
Limb Bud ◽  
Type I ◽  
Type Ii ◽  
Mrna Accumulation ◽  
Rna Probes

During limb development, type I collagen disappears from the region where cartilage develops and synthesis of type II collagen, which is characteristic of cartilage, begins. In situ hybridization using antisense RNA probes was used to investigate the spatial localization of type I and type II collagen mRNAs. The distribution of the mRNA for type II collagen corresponded well with the pattern of type II collagen synthesis, suggesting control at the level of transcription and mRNA accumulation. In contrast, the pattern of mRNA for type I collagen remained more or less uniform and did not correspond with the synthesis of the protein, suggesting control primarily at the level of translation or of RNA processing.

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