scholarly journals Matrix metalloproteinase 14 is required for fibrous tissue expansion

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Susan H Taylor ◽  
Ching-Yan Chloé Yeung ◽  
Nicholas S Kalson ◽  
Yinhui Lu ◽  
Paola Zigrino ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Collagen Fibril ◽  
Type I Collagen ◽  
Fibrous Tissue ◽  
Tissue Expansion ◽  
Collagen Fibrils ◽  
Collagen I ◽  
Type I ◽  
Tendon Development

Type I collagen-containing fibrils are major structural components of the extracellular matrix of vertebrate tissues, especially tendon, but how they are formed is not fully understood. MMP14 is a potent pericellular collagenase that can cleave type I collagen in vitro. In this study, we show that tendon development is arrested in Scleraxis-Cre::Mmp14 lox/lox mice that are unable to release collagen fibrils from plasma membrane fibripositors. In contrast to its role in collagen turnover in adult tissue, MMP14 promotes embryonic tissue formation by releasing collagen fibrils from the cell surface. Notably, the tendons grow to normal size and collagen fibril release from fibripositors occurs in Col-r/r mice that have a mutated collagen-I that is uncleavable by MMPs. Furthermore, fibronectin (not collagen-I) accumulates in the tendons of Mmp14-null mice. We propose a model for cell-regulated collagen fibril assembly during tendon development in which MMP14 cleaves a molecular bridge tethering collagen fibrils to the plasma membrane of fibripositors.

scholarly journals Formation of collagen fibrils by enzymic cleavage of precursors of type I collagen in vitro.

1984 ◽  
Vol 259 (15) ◽  
pp. 9891-9898 ◽  
Author(s):  
M Miyahara ◽  
K Hayashi ◽  
J Berger ◽  
K Tanzawa ◽  
F K Njieha ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Collagen Fibrils ◽  
Type I

scholarly journals Matrix fully loaded: Assembly and secretion of collagen fibrils

2003 ◽  
Vol 25 (5) ◽  
pp. 11-13
Author(s):  
Karl E. Kadler ◽  
Elizabeth G. Canty ◽  
Yinhui Lu
Keyword(s):  
Extracellular Matrix ◽  
Plasma Membrane ◽  
Secretory Pathway ◽  
Type I Collagen ◽  
Fibril Formation ◽  
Collagen Fibrils ◽  
Type I ◽  
Small Proteins ◽  
Unpublished Work ◽  
Structural Work

The secretory pathway operates like a well-oiled machine when it comes to secreting small proteins. But how does it cope with stiff rod-like molecules such as type I collagen, which spontaneously self-assembles into the millimetre-long collagen fibrils that are characteristic of the extracellular matrix (ECM)? A recent study in our laboratory shows that the secretory pathway adapts exquisitely to intracellular fibril formation by creating tubular vesicles that dock to specialized secretory nozzles in the plasma membrane (E.G. Canty, Y. Lu, R.M. Meadows, M. Shaw, D.F. Holmes and K.E. Kadler, unpublished work). This article gives a brief account of the biochemical and structural work that led up to these new observations.

Proteoglycan-collagen interactions. Structure in the amorphous ground substance

1988 ◽  
Vol 53 (1) ◽  
pp. 202-208 ◽  
Author(s):  
John E. Scott
Keyword(s):  
Collagen Fibril ◽  
Type I Collagen ◽  
Collagen Fibrils ◽  
Histochemical Method ◽  
Ground Substance ◽  
Type I ◽  
Specific Interactions ◽  
Different Tissues

Glycosaminoglycans occur in vivo outside the collagen fibrils. In this perifibrillar space specific interactions between proteoglycans and the collagen fibrils lead to the formation of an organized structure. Different tissues were examined by an electron histochemical method and it was concluded that the single proteoglycans have specific loci of association with the type I collagen fibril and are arrayed orthogonally in respect to the fibrils.

Organization and characterization of fibrillar collagens in fish scales in situ and in vitro

1992 ◽  
Vol 103 (1) ◽  
pp. 273-285 ◽  
Author(s):  
L. ZYLBERBERG ◽  
J. BONAVENTURE ◽  
L. COHEN-SOLAL ◽  
D. J. HARTMANN ◽  
J. BEREITERHAHN
Keyword(s):  
Cyanogen Bromide ◽  
Type I Collagen ◽  
Collagen Fibrils ◽  
Type I ◽  
Fish Scales ◽  
Fibrillar Collagens ◽  
Collagen Genes

The characterization of the fibrillar collagens and the cellular control of their spatial deposition were studied in fish scales using immunofluorescence, electron microscopy, electrophoretic and HPLC analyses, immunoprecipitation and hybridization with cDNA probes. This study was carried out on undisturbed and regenerating scales in situ and in organ and cell cultures from regenerating scales. The hyposquamal scleroblasts forming a pseudoepithelium show an apico-basal polarization and synthesize thick collagen fibrils (100 nm) organized in a plywood pattern as long as the integrity of the cell-cell and cell-collagenous matrix contacts are preserved. In culture, scleroblasts become fibroblastlike and produce an unordered meshwork of thin collagen fibrils (30 nm). Comparison of the synthesized collagens in culture with those extracted from the scales indicates that culture conditions modify fibrillogenesis but do not change the expression of fibrillar collagen genes. Type I collagen, the predominent component, is associated with the minor type V collagen. Type III collagen was not present. In type I collagen, a third chain, α3 chain, was identified. The ratio between the 3 chains suggests the coexistence of two heterotrimers (α(I))2 α2(I) and αl(I) α2(I) α3(I). Analysis by HPLC and electrophoresis of the cyanogen bromide-derived peptides obtained from the purified a3 chain support the hypothesis that α(I) and α3(I) chains are encoded by two different genes. The presence of the two types of heterotrimers in vivo as well as in vitro could correspond to an innate property of the goldfish scleroblasts. Despite the fact that teleost cyanogen bromide-derived peptides differ from those of higher vertebrates, homologies with the mammalian collagen genes (human, for example) are sufficient to allow the detection of mRNA transcripts for αl(I), α2(I) and α2(V) from confluent scleroblast cultures with human probes.

scholarly journals Intra-Articular Injection of Hydrolyzed Collagen to Treat Symptoms of Knee Osteoarthritis. A Functional In Vitro Investigation and a Pilot Retrospective Clinical Study

2019 ◽  
Vol 8 (7) ◽  
pp. 975 ◽  
Author(s):  
Paola De Luca ◽  
Alessandra Colombini ◽  
Giulia Carimati ◽  
Michelangelo Beggio ◽  
Laura de Girolamo ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Type I Collagen ◽  
Fibrous Tissue ◽  
Type I ◽  
Collagen Deposition ◽  
Symptomatic Knee Osteoarthritis ◽  
In Vitro Investigation ◽  
Symptomatic Knee ◽  
Retrospective Clinical Study

Among all joints affected, knee osteoarthritis has a prevalence of about 10% in men and 13% in women over 60 years old. Knee osteoarthritis has high economic and social costs and may have a devastating impact on patient quality of life. Treatment of symptomatic knee Osteoarthritis may involve oral or topical administration of non-steroidal anti-inflammatory drugs or intra-articular injection of corticosteroids. Recently, a novel injectable collagen formulation (ChondroGrid) consisting of bovine hydrolyzed <3 kDa type I collagen has been developed and is currently available on the market as an injectable medical device. The primary objective of this study was to investigate the in vitro and in vivo effects of ChondroGrid in treating knee osteoarthritis symptoms to assess its safety and performance. Viability and proliferation of ChondroGrid-exposed human chondrocytes derived from five donors were assessed through the Alamar Blue/CyQuant assays. Their expression of MMP1/MMP3 and TIMP1/TIMP3 was then assessed through RT-PCR and that of TGFβ1, IGF-I, and VEGF using ELISA assays. Shape and ECM deposition were assessed using the Bern score after a 28-day ChondroGrid exposure, and collagen deposition was assessed using immunostaining. Records of 20 patients affected by Kellgren Lawrence grade 1 to 4 knee osteoarthritis who received three 4mg/2mL ChondroGrid injections 2 weeks apart were then retrospectively assessed to compare VAS, Lequesne, and WOMAC scores collected before and 15, 45, and 225 days after the first injection. ChondroGrid had no effects on the markers under consideration, but induced type-II and inhibited type-I collagen deposition; the Bern score was higher when cells were cultured with ChondroGrid. Patients experienced a 44% Lequesne score and a 55% VAS at moving score reduction. All other scores decreased >70%. ChondroGrid may prompt chondrocytes to produce hyaline cartilage, prevent fibrous tissue formation, and be a safe and effective adjuvant to treat symptomatic knee osteoarthritis.

scholarly journals Structure–function studies on Hsp47: pH-dependent inhibition of collagen fibril formation in vitro

2000 ◽  
Vol 349 (3) ◽  
pp. 877-883 ◽  
Author(s):  
Christy A. THOMSON ◽  
Vettai S. ANANTHANARAYANAN
Keyword(s):  
Endoplasmic Reticulum ◽  
Collagen Fibril ◽  
Type I Collagen ◽  
Fibril Formation ◽  
Molar Ratio ◽  
Functional Assay ◽  
Type I ◽  
Ph Dependent ◽  
Ph Range

Hsp47, a 47kDa heat shock protein whose expression level parallels that of collagen, has been regarded as a collagen-specific molecular chaperone. Studies from other laboratories have established the association of Hsp47 with the nascent as well as the triple-helical procollagen molecule in the endoplasmic reticulum and its dissociation from procollagen in the Golgi. One of several roles suggested for Hsp47 in collagen biosynthesis is the prevention of aggregation of procollagen in the endoplasmic reticulum. However, no experimental evidence has been available to verify this suggestion. In the present study we have followed the aggregation of mature triple-helical collagen molecules into fibrils by using turbidimetric measurements in the absence and presence of Hsp47. In the pH range 6–7, fibril formation of type I collagen, as monitored by turbidimetry, proceeds with a lag of approx. 10min and levels off by approx. 60min. The addition of Hsp47 at pH 7 effectively inhibits fibril formation at and above a 1:1 molar ratio of Hsp47 to triple-helical collagen. This inhibition is markedly pH-dependent, being significantly diminished at pH 6. CD and fluorescence spectral data of Hsp47 in the pH range 4.2–7.4 reveal a significant alteration in its structure at pH values below 6.2, with a decrease in α-helix and an increase in β-structure. This conformational change is likely to be the basis of the decreased binding of Hsp47 to collagen in vitro at pH 6.3 as well as its inability to inhibit collagen fibril formation at this pH. Our results also provide a functional assay for Hsp47 that can be used in studies on collagen and Hsp47 interactions.

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