Elastin metabolism during recovery from impaired crosslink formation

Tinker, David O.; Romero-Chapman, Nadia; Reiser, Karen M.; Hyde, Dallas M.; Rucker, Robert B.

doi:10.1016/0003-9861(90)90267-3

Cited by 22 publications

(13 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dietary copper de®ciency rapidly depresses lysyl oxidase activity in chick aorta [Harris et al, 1974] and lung [Harris, 1986] causing increases in non-cross-linked collagen and elastin. In this context, resistance to proteolysis occurs within a short period of copper repletion in several organisms [Tinker et al, 1990]. With these facts in mind, we speculate that the presence of copper in the microenvironment may modify ECM maturation and consequently the proliferation and differentiation processes.…”

Section: Discussionmentioning

confidence: 98%

Modulation of the proliferation and differentiation of human mesenchymal stem cells by copper

Rodríguez

Rı́os

González

2002

J of Cellular Biochemistry

193

View full text Add to dashboard Cite

Copper plays important functional roles in bone metabolism and turnover. It is known that it is essential for normal growth and development of the skeleton in humans and in animals. Although at present the exact role that copper plays in bone metabolism is unknown, bone abnormalities are a feature of severe copper deficiency. Osteoblasts are derived from mesenchymal stem cells (MSCs) present in bone marrow stroma, which are able to differentiate into bone, adipocytes, and other cell phenotypes. Excess adipogenesis in postmenopausal women may occur at the expense of osteogenesis and, therefore, may be an important factor in the fragility of postmenopausal bone. The purpose of this study was to evaluate whether an increase of the extracellular concentration of copper affects the ability of MSCs to differentiate into osteoblasts or adipocytes. The results showed that copper modified both the differentiation and the proliferative activity of MSCs obtained from postmenopausal women. Copper (50 microM) diminished the proliferation rate of MSCs, increasing their ability to differentiate into the osteogenic and the adipogenic lineages. Copper induced a 2-fold increase in osteogenic differentiation of MSCs, measured as a increase in calcium deposition. Copper (5 and 50 microM) diminished the expression of alkaline phosphatase (50 and 80%, respectively), but induced a shift in the expression of this enzyme to earlier times during culture. Copper also induced a 1.3-fold increase in the adipogenic differentiation of MSCs. It is concluded that copper stimulates MSC differentiation, and that this is preferentially towards the osteogenic lineage.

show abstract

Section: Discussionmentioning

confidence: 98%

Modulation of the proliferation and differentiation of human mesenchymal stem cells by copper

Rodríguez

Rı́os

González

2002

J of Cellular Biochemistry

193

View full text Add to dashboard Cite

show abstract

“…In fact, the crosslinking is essential to strengthen the growing elastic fibers. When the lysyl oxidase activity is inhibited, the level of crosslinked amino acids strongly decreases and it is followed by a reduced elastin accumulation in tissues . Also in native vessels, medial smooth muscle cells produce ECM with specific architecture which provides elastic recoil (elastic fibers) and tensile strength (collagen fibers) necessary to maintain adequate structural mechanical properties.…”

Section: Discussionmentioning

confidence: 99%

Human elastin polypeptides improve the biomechanical properties of three‐dimensional matrices through the regulation of elastogenesis

Boccafoschi

Ramella

Sibillano

et al. 2014

J Biomedical Materials Res

View full text Add to dashboard Cite

The replacement of diseased tissues with biological substitutes with suitable biomechanical properties is one of the most important goal in tissue engineering. Collagen represents a satisfactory choice for scaffolds. Unfortunately, the lack of elasticity represents a restriction to a wide use of collagen for several applications. In this work, we studied the effect of human elastin-like polypeptide (HELP) as hybrid collagen-elastin matrices. In particular, we studied the biomechanical properties of collagen/HELP scaffolds considering several components involved in ECM remodeling (elastin, collagen, fibrillin, lectin-like receptor, metalloproteinases) and cell phenotype (myogenin, myosin heavy chain) with particular awareness for vascular tissue engineering applications. Elastin and collagen content resulted upregulated in collagen-HELP matrices, even showing an improved structural remodeling through the involvement of proteins to a ECM remodeling activity. Moreover, the hybrid matrices enhanced the contractile activity of C2C12 cells concurring to improve the mechanical properties of the scaffold. Finally, small-angle X-ray scattering analyses were performed to enable a very detailed analysis of the matrices at the nanoscale, comparing the scaffolds with native blood vessels. In conclusion, our work shows the use of recombinant HELP, as a very promising complement able to significantly improve the biomechanical properties of three-dimensional collagen matrices in terms of tensile stress and elastic modulus.

show abstract

“…41 Deficiency of nutritional copper has been linked to vascular lesions and development of aneurysms. [42][43][44] One study showed that, in the presence of HA, low doses (0.01 M) of CuSO 4 enhance tissue vascularization. 45 Dahl et al investigated the singular effects of increasing medium Cu 2þ ion concentration on matrix crosslinking efficiency in an engineered vascular-like tissue and showed that increasing levels of cross-links formed.…”

Section: Discussionmentioning

confidence: 99%

Biomimetic Regeneration of Elastin Matrices Using Hyaluronan and Copper Ion Cues

Kothapalli

Ramamurthi

2009

Tissue Engineering Part A

View full text Add to dashboard Cite

Current efforts to tissue engineer elastin-rich vascular constructs and grafts are limited because of the poor elastogenesis of adult vascular smooth muscle cells (SMCs) and the unavailability of appropriate cues to upregulate and enhance cross-linking of elastin precursors (tropoelastin) into organized, mature elastin fibers. We earlier showed that hyaluronan (HA) fragments greatly enhance tropo-and matrix-elastin synthesis by SMCs, although the yield of matrix elastin is low. To improve matrix yields, here we investigate the benefits of adding copper (Cu 2+ ) ions (0.01 M and 0.1 M), concurrent with HA (756-2000 kDa), to enhance lysyl oxidase (LOX)-mediated elastin cross-linking machinery. Although absolute elastin amounts in test groups were not different from those in controls, on a per-cell basis, 0.1 M of Cu 2+ ions slowed cell proliferation (5.6 AE 2.3-fold increase over 21 days vs 22.9 AE 4.2-fold for non-additive controls), stimulated synthesis of collagen (4.1 AE 0.4-fold), tropoelastin (4.1 AE 0.05-fold) and cross-linked matrix elastin (4.2 ± 0.7-fold). LOX protein synthesis increased 2.5 times in the presence of 0.1 M of Cu 2+ ions, and these trends were maintained even in the presence of HA fragments, although LOX functional activity remained unchanged in all cases. The abundance of elastin and LOX in cell layers cultured with 0.1 M of Cu 2+ ions and HA fragments was qualitatively confirmed using immunoflourescence. Scanning electron microscopy images showed that SMC cultures supplemented with 0.1 M of Cu 2+ ions and HA oligomers and large fragments exhibited better deposition of mature elastic fibers (*1 mm diameter). However, 0.01 M of Cu 2+ ions did not have any beneficial effect on elastin regeneration. In conclusion, the results suggest that supplying 0.1 M of Cu 2+ ions to SMCs to concurrently (a) enhance per-cell yield of elastin matrix while allowing cells to remain viable and synthetic and not density-arrested in long-term culture because of their moderating effects on otherwise rapid cell proliferation and (b) provide additional benefits of enhanced elastin fiber formation and cross-linking within these tissue-engineered constructs.

show abstract

Elastin metabolism during recovery from impaired crosslink formation

Cited by 22 publications

References 29 publications

Modulation of the proliferation and differentiation of human mesenchymal stem cells by copper

Modulation of the proliferation and differentiation of human mesenchymal stem cells by copper

Human elastin polypeptides improve the biomechanical properties of three‐dimensional matrices through the regulation of elastogenesis

Biomimetic Regeneration of Elastin Matrices Using Hyaluronan and Copper Ion Cues

Contact Info

Product

Resources

About