Type I Collagen

The propeptides PICP and PINP are derived from the synthesis of type I collagen, a major matrix protein of bone and soft tissues. The aim of this cross-sectional study was to investigate their value as indicators of the aggressivity of breast cancer. Serum PINP, PICP, and total alkaline phosphatase were determined from 89 breast cancer patients. Forty had major bone and/or soft tissue metastases with an aggressive disease course: the progressive disease (PD) group. Forty-nine had either none or minor bone and/or soft tissue metastases with a stable clinical course: the stable disease group (SD). The mean value of PINP in the PD group was 7.2 times higher than that in the SD group (276 +/- 79 microg/l versus 38 +/- 3 microg/l, respectively; P = 0.005), whereas PICP mean value was only 1.7 times higher in the PD group (174 +/- 20 microg/l versus 100 +/- 5 microg/l; P = 0.001). The ratio of PICP to PINP was 1.02 +/- 0.07 in the PD group and 3.07 +/- 0.18 in the SD group (P < 0.001)....

The aim of the present study was to evaluate the effect of hemodialysis and renal failure on serum bone markers. Serum total alkaline phosphatase (TAP), procollagen type I aminoterminal propeptide (PINP), and Β-carboxyterminal telopeptide of type I collagen (Β-CTX), as well as intact parathyroid hormone (iPTH), creatinine, and total protein were measured in 14 patients with endstage renal disease (ESRD) before and at 1, 2, and 4 h during a hemodialysis session, and at the same sampling interval in 6 renal transplant recipients. The results were compared to those obtained in 20 healthy adults. All patients showed increased baseline mean values of PINP, Β-CTX, and iPTH. Β-CTX differed significantly between hemodialysis patients and renal transplant recipients. TAP and Β-CTX were the only markers which correlated with iPTH (P ≪ 0.05) and creatinine values (P ≪ 0.001), respectively. Renal transplant recipients did not show significant variations in the evolution of mean values of bone markers throughout the study, whereas, during the dialysis period, all the bone markers analyzed in the study showed a significant change. The change differed depending on the marker considered: Β-CTX showed a significant decrease at the end of the session, TAP increased at this time and, although PINP showed an initial increase during hemodialysis, no significant changes were observed at the end of the session. We conclude that bone markers are significantly influenced by hemodialysis, especially serum TAP and Β-CTX. ESRD is associated with an increase in these bone markers, in some cases related to iPTH values and in others to glomerular function. These findings should be taken into account when evaluating bone markers in these patients.

Acid soluble collagen (ASC) was extracted from the skins of young and adult Nile perch (Lates niloticus) using 0.5 M acetic acid and precipitation with 0.9 M NaCl. The ASC yields, on a dry weight basis, were 63.1 and 58.7%, respectively for young and adult fish skins. SDS-PAGE showed that the collagens contained two alpha components (α1 and α2). ASC from Nile perch was found to contain more imino acids (19.3 and 20.0%, respectively, for young and adult fish) than most fish species. The denaturation temperature for the collagens from the skins of young and adult Nile perch was determined to be 36 °C, which is also higher than that for most other fish species. Fourier transform infrared spectroscopy showed a higher degree of molecular order in ASC from adult than from young Nile perch. The results indicate that age-related changes in Nile perch skin collagen are not very pronounced, probably because there is minimal development of mature cross-links.

Chronic leg wounds are characterized by defective remodeling of the extracellular matrix, failure of reepithelialization, and prolonged inflammation. The hypothesis that this defective extracellular matrix remodeling is associated with phenotypic differences in the activity of the matrix ...

The influence of ionic substituents in calcium phosphates intended for bone and tooth replacement biomedical applications is an important research topic, owing to the essential roles played by trace elements in biological processes. The present study investigates the mechanical and biological evaluation of ionic doped hydroxyapatite/β-tricalcium phosphate mixtures which have been prepared by a simple aqueous precipitation method. Heat treating the resultant calcium phosphates in a carbonated atmosphere led to the formation of ionic doped carbonated hydroxyapatite/β-tricalcium phosphate mixtures containing the essential ions of biological apatite. The structural analysis determined by Rietveld refinement confirmed the presence of hydroxyapatite as the main phase, together with a considerable amount of β-tricalcium phosphate. Such phase assemblage is essentially due to the influence of substituted ions during synthesis. The results from mechanical tests proved that carbonate substitutions are detrimental for the mechanical properties of apatite-based ceramics. In vitro proliferation assays of osteoblastic-like cells (MC3T3-E1 cell line) to powders revealed that carbonate incorporation can either delay or accelerate MC3T3 proliferation, although reaching the same proliferation levels as control cells after 2 weeks in culture. Further, the powders enable pre-osteoblastic differentiation in a similar manner to control cells, as indirectly measured by ALP activity and Type-I collagen medium secretion.

As current aesthetic surgical techniques become more standardized and results more predictable, a fine scar may be the demarcating line between acceptable and unacceptable aesthetic results. With this in mind, a scar management program has been adopted based on the modalities of wound support, hydration, and hastened maturity, all factors gleaned from scientific evidence published over the past 25 years. Tension on a scar in one axis will result in a stretched scar, probably initiated by neutrophils and their neutral proteases [18,26]. Tension on a scar from many directions or intermittently will result in a hypertrophic scar, possibly initiated by lymphocytes but definitely related to a prolongation of the inflammatory process, with increased fibroblast activity and overabundant extracellular matrix secretion [24,26]. The common initiating factor is the tension on the scar, and the critical element needed to counteract this tension is scar support. Clinical experience has shown us that the most reliable way to support a scar is by using microporous tape. Hydration is a second beneficial influence on scar control and is the basis of the use of silicone sheeting and gel [7,29,36]. Alpha Centella cream has two main components. The first is an extract from the plant Bulbine frutescens. This increases hydration under the tape by leaving a layer of fatty vesicles of glycoprotein on the skin surface. This also has antibacterial properties. The second component is the principal terpenoids extracted from the Centella asiatica plant. These include asiatic acid, madecassic acid, and asiaticoside. Centella asiatica has been documented to aid wound healing in a large number of scientific reports [5,12,21,22,33,34,40]. The most beneficial effect appears to be the stimulation of maturation of the scar by the production of type I collagen [4,19] and the resulting decrease in the inflammatory reaction and myofibroblast production. Thus these components have been incorporated into the formulation of a scar management program. This publication reviews much of the available literature relating to scar management and describes the formulation and use of a scar management program based on this information.

Schizophyllan is a natural polysaccharide, produced by fungi of the genus Schizophyllum. Periodate oxidation specifically cleaves the vicinal glycols in schizophyllan to form their dialdehyde derivatives. The present study investigates the interaction of scleraldehyde with Type I collagen membrane. The formation of the inter and intra interaction between scleraldehyde and the collagen fibres results in significant increase in viscosity of collagen. Crosslinking efficiency of scleraldehyde was found to increase with concentration of scleraldehyde. Scleraldehyde interacted collagen membrane exhibited an increase in thermal stability by 29 °C at pH 8. The gelling time of collagen fibrils was found to decrease with increase in concentration of scleraldehyde due to shift in nucleation centre. Swelling degree of collagen membrane was also found to decrease with increase in concentration of scleraldehyde. Scleraldehyde treated collagen membrane exhibited 93% resistance to collagenase. The modified collagen membrane exhibited non-toxicity towards the fibroblasts cells. The modified collagen membrane by scleraldehyde finds application as a stabilizing agent in scaffold preparation.► Schizophyllan is a natural polysaccharide, produced by fungi of the genus Schizophyllum. ► Modified collagen fibres results in significant increase in viscosity of collagen. ► Scleraldehyde interacted collagen exhibited thermal stability of 89 °C. ► Scleraldehyde treated collagen membrane exhibited 93% resistance to collagenase.

Osteochondral articular defects represent a key concern in orthopedic surgery. The objective of this pilot clinical study was to test safety and performance of a newly developed type-I collagen-hydroxyapatite (HA) nanostructural bio-mimetic osteochondral (O.C.) scaffold which reproduces cartilage-subchondral bone morphology. A gradient composite O.C. scaffold, based on type-I collagen-HA, was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles at physiological conditions. In previous in vitro and animal studies we tested a novel nano-structured three-layer collagen-hydroxyapatite biomaterial for osteochondral reconstruction and obtained good results in terms of both cartilage and bone tissue formation. We observed same macroscopic, histological and radiographic results when implanting scaffold loaded with autologous chondrocytes or scaffold alone. The scaffold was able to induce an in situ regeneration through stem cells coming from the surrounding bone marrow. Thus, we applied this innovative scaffold as a cell-free approach into clinical practice. 30 cases (9F, 21M, mean age 29,3 years) with knee osteochondral lesions were treated with scaffold implantation from January 2007 to July 2007. The lesions size went from 2 cm2 to 6 cm2. All patients achieved minimum 1 year follow up and were clinically evaluated using the International Repair Cartilage Society score. IKDC objective score improved after 1 year showing a normal or nearly normal knee in 80% of patients at 1 year of follow up. Similar results were obtained with the IKDC subjective score and with Tegner score. Cases with previous surgery had the worst results, while associated surgery doesn’t influenced significantly the clinical outcome. 1 case failed and was reoperated. MRI evaluation demonstrated good bone and cartilage formation and only in the failed case no integration of the graft was found. This open one-step surgery was used for the treatment of chondral and osteochondral defects. The results of this technique at short follow-up are very encouraging and show satisfactory results even in big ostechondral defects.

The development of new vanadium derivatives with organic ligands, which improve the beneficial actions (insulin-mimetic, antitumoral) and decrease the toxic effects, is of great interest. A good candidate for the generation of a new vanadium compound is the flavonoid quercetin because of its own anticarcinogenic effect. The complex [VO(Quer)2EtOH]n (QuerVO) has been synthesized and characterized by means of different spectroscopic techniques (UV–vis, Fourier transform IR, electron paramagnetic resonance) and its magnetic and stability properties. The inhibitory effect on bovine alkaline phosphatase (ALP) activity has been tested for the free ligand, the complex as well as for the vanadyl(IV) (comparative purposes). The biological activity of the complex on the proliferation of two osteoblast-like cells in culture, a normal one (MC3T3E1) and a tumoral one (UMR106), has been compared with that of the vanadyl(IV) cation and quercetin. The differentiation osteoblast markers ALP specific activity and collagen synthesis have been also tested. In addition, the effect of QuerVO on the activation of the extracellular regulated kinase (ERK) pathway is reported. The bone antitumoral effect of quercetin alone was established with the cell proliferation assays (it inhibits the proliferation of the tumoral cells and does not exert any effect on the normal osteoblasts). Moreover, the complex exerts osteogenic effects since it stimulates the type I collagen production and is a weak inhibitory agent upon ALP activity. Finally, QuerVO stimulated the ERK phosphorylation in a dose–response manner and this activation seems to be involved as one of the possible mechanisms for the biological effects of the complex.

We have previously demonstrated that halofuginone, a low molecular weight quinazolinone alkaloid, is a potent inhibitor of collagen a1(I) and matrix metalloproteinase 2 (MMP-2) gene expres- sion. Halofuginone also effectively suppresses tu- mor progression and metastasis in mice. These re- sults together with the well-documented role of extracellular matrix (ECM) components and matrix degrading enzymes in formation of new blood

ABSTRACTGaucher disease is caused by the inherited deficiency of glucocerebrosidase, a lysosomal enzyme responsible for the cleavage of glucosylceramide. In addition to organomegaly and hematological abnormalities, type 1 (nonneuronopathic) disease is characterized by insidiously progressive and often severe skeletal involvement. We investigated the applications of biochemical markers of bone turnover in the evaluation of skeletal lesions in type 1 Gaucher disease patients. Serum osteocalcin, a marker of osteoblastic bone formation, and type I collagen C-terminal telopeptide, a marker of osteoclastic bone resorption, were measured in 16 type 1 Gaucher disease patients and in 29 age-matched controls. Our results indicate a significant decrease of both osteocalcin (11.13 ± 2.27 ng/ml) and type I collagen C-terminal telopeptide (3617.62 ± 536.69 ng/ml) values in patients with Gaucher disease, compared to the unaffected controls (38.67 ± 6.24 ng/ml and 6808.57 ng/ml ± 865.66, respectively). These low values were observed in all patients, irrespective of their age, indicating a marked failure of both osteoblastic and osteoclastic functions in Gaucher disease. Significant differences in the mean serum values of biochemical bone turnover markers were found in different evolutional stages of bone involvement. We conclude that measurement of serum biochemical markers of bone turnover can be used as an auxiliary tool in the diagnosis, staging, and monitoring the skeletal lesions in Gaucher disease, in conjunction with imaging methods and bone densitometry measurements.

Matrix metalloproteinase-2 (MMP-2), a zymogen requiring proteolytic activation for catalytic activity, has been implicated broadly in the invasion and metastasis of many cancer model systems, including human breast cancer (HBC). MMP-2 has been immunolocalized to carcinomatous human breast, where the degree of activation of MMP-2 correlates well with tumor grade and patient prognosis. Using Matrigel assays, we have stratified HBC cell lines for invasivenessin vitro, and compared this to their potential for metastatic spread in nude mice. HBC cell lines expressing the mesenchymal marker protein vimentin were found to be highly invasivein vitro, and tended to form metastases in nude mice. We have further discovered that culture on collagen-I gels (VitrogenTM; Vg) induces MMP-2-activator in highly invasive but not poorly invasive HBC cell lines. As seen for other MMP-2-activator inducing regimens, this induction requires protein synthesis and an intact MMP-2 hemopexin-like domain, appears to be mediated by a cell surface activity, and can be inhibited by metalloproteinase inhibitors. The induction is highly specific to collagen I, and is not seen with thin coatings of collagen I, collagen IV, laminin, or fibronectin, or with 3-dimensional gels of laminin, Matrigel, or gelatin. This review focuses on collagen I and MMP-2, their localization and source in HBC, and their relationship(s) to MMP-2 activation and HBC metastasis. The relevance of collagen I in activation of MMP-2in vivo is discussed in terms of stromal cell: tumor cell interaction for collagen I deposition, MMP-2 production, and MMP-2-activation. Such cooperativity may existin vivo for MMP-2 participation in HBC dissemination. A more complete understanding of the regulation of MMP-2-activator by type I collagen may provide new avenues for improved diagnosis and prognosis of human breast cancer.

In this study, we analyzed the changes in biochemical markers of bone turnover in five patients with hypophosphatemic osteomalacia. The following bone markers were evaluated: among bone formation markers, total alkaline phosphatase (TAP), bone alkaline phosphatase (BAP), osteocalcin (bone Gla protein, BGP) and procollagen type I N propeptide (PINP); among bone resorption markers, serum β C-terminal cross-linked telopeptide of type I collagen (s-CTx), urinary hydroxyproline (HYP), and N-terminal and α and β C-terminal cross-linked telopeptides of collagen (NTx and α- and β-CTx). In addition, the α/β-CTx ratio was evaluated. TAP and BAP were the markers with the highest increase in both frequency and magnitude. Conversely, BGP values were low in all patients. Collagen-related markers were slightly increased in nearly half of the patients. Among them, PINP showed the highest proportion of increased values. The α/β-CTx ratio was within normal values in all patients. In conclusion, TAP and BAP seem to be the best bone markers in the diagnostic evaluation of hypophosphatemic osteomalacia. In addition, their high values associated with low levels of BGP provide an even more reliable biochemical profile of this disorder, when associated with the classic mineral and skeletal homeostasis abnormalities.