Increased cartilage type II collagen degradation in patients with osteogenesis imperfecta used as a human model of bone type I collagen alterations

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.

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

Development ◽

10.1242/dev.117.1.245 ◽

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)

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

Development ◽

10.1242/dev.103.1.111 ◽

1988 ◽

Vol 103 (1) ◽

pp. 111-118 ◽

Cited By ~ 1

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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Changes in Cytokines and Aggrecan ARGS Neoepitope in Synovial Fluid and Serum and in C-Terminal Crosslinking Telopeptide of Type II Collagen and N-Terminal Crosslinking Telopeptide of Type I Collagen in Urine Over Five Years After Anterior Cruciate Ligame

Arthritis & Rheumatology ◽

10.1002/art.39146 ◽

2015 ◽

Vol 67 (7) ◽

pp. 1816-1825 ◽

Cited By ~ 45

Author(s):

André Struglics ◽

Staffan Larsson ◽

Nobuyuki Kumahashi ◽

Richard Frobell ◽

L. Stefan Lohmander

Keyword(s):

Synovial Fluid ◽

Type I Collagen ◽

Type Ii Collagen ◽

Type I ◽

Type Ii ◽

Anterior Cruciate

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Modulation of the rabbit chondrocyte phenotype by retinoic acid terminates type II collagen synthesis without inducing type I collagen: The modulated phenotype differs from that produced by subculture

Developmental Biology ◽

10.1016/0012-1606(86)90096-5 ◽

1986 ◽

Vol 118 (1) ◽

pp. 296-305 ◽

Cited By ~ 57

Author(s):

Paul D. Benya ◽

Silvia R. Padilla

Keyword(s):

Retinoic Acid ◽

Collagen Synthesis ◽

Type I Collagen ◽

Type Ii Collagen ◽

Type I ◽

Type Ii ◽

Chondrocyte Phenotype

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Protective Effects of Annatto Tocotrienol and Palm Tocotrienol-Rich Fraction on Chondrocytes Exposed to Monosodium Iodoacetate

Applied Sciences ◽

10.3390/app11209643 ◽

2021 ◽

Vol 11 (20) ◽

pp. 9643

Author(s):

Kok-Lun Pang ◽

Norzana Abd Ghafar ◽

Ima Nirwana Soelaiman ◽

Kok-Yong Chin

Keyword(s):

Type I Collagen ◽

Type Ii Collagen ◽

Collagen Type I ◽

Type I ◽

Protective Effects ◽

Type Ii ◽

Chondrocyte Viability ◽

Monosodium Iodoacetate ◽

Α Level ◽

Tocotrienol Rich Fraction

Background: This study aimed to compare the chondroprotective efficacy and mechanism of annatto tocotrienol (AnTT) and palm tocotrienol-rich fraction (PT3) using SW1353 chondrocytes treated with monosodium iodoacetate (MIA). Methods: The chondrocytes were incubated with AnTT or PT3 in advance or concurrently with MIA for 24 h. The viability of the cells was tested with an MTT assay. The 8-isoprostane F2-α, extracellular matrix proteins, metalloproteinase and sex-determining region Y box protein 9 (SOX9) levels were determined using immunoassays. Results: AnTT and PT3 reversed an MIA-induced decrease in chondrocyte viability when incubated together with MIA (p < 0.05). Prior incubation with both mixtures did not produce the same effects. AnTT and PT3 cotreatment could suppress 8-isoprostane F2-α level in chondrocytes exposed to MIA (p < 0.01). Co-exposure to tocotrienols and MIA increased the type II collagen/type I collagen ratio in chondrocytes (p < 0.01). In addition, the co-exposure of AnTT and MIA for 24 h significantly upregulated SOX9, type II collagen and aggrecan levels (p < 0.05), which was not observed with co-exposure of PT3 and MIA, AnTT or PT3 exposure alone. Conclusion: AnTT and PT3 could prevent a reduction in chondrocyte viability following MIA exposure by reducing oxidative stress. In addition, AnTT might induce self-repair and anabolic activities in chondrocytes challenged with MIA.

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Interaction between proteoglycan subunit and type II collagen from bovine nasal cartilage, and the preferential binding of proteoglycan subunit to type I collagen

Biochemical Journal ◽

10.1042/bj1530259 ◽

1976 ◽

Vol 153 (2) ◽

pp. 259-264 ◽

Cited By ~ 26

Author(s):

V Lee-Own ◽

J C Anderson

Keyword(s):

Gel Electrophoresis ◽

Type I Collagen ◽

Polyacrylamide Gel Electrophoresis ◽

Type Ii Collagen ◽

Type I ◽

Type Ii ◽

Nasal Cartilage ◽

Preferential Binding ◽

Calf Skin

We studied the interaction of proteoglycan subunit with both types I and II collagen. All three molecular species were isolated from the ox. Type II collagen, prepared from papain-digested bovine nasal cartilage, was characterized by gel electrophoresis, amino acid analysis and CM-cellulose chromatography. By comparison of type I collagen, prepared from papain-digested calf skin, with native calf skin acid-soluble tropocollagen, we concluded that the papain treatment left the collagen molecules intact. Interactions were carried out at 4 degrees C in 0.06 M-sodium acetate, pH 4.8, and the results were studied by two slightly different methods involving CM-cellulose chromatography and polyacrylamide-gel electrophoresis. It was demonstrated that proteoglycan subunit, from bovine nasal cartilage, bound to cartilage collagen. Competitive-interaction experiments showed that, in the presence of equal amounts of calf skin acid-soluble tropocollagen (type I) and bovine nasal cartilage collagen (type II), proteoglycan subunit bound preferentially to the type I collagen. We suggest from these results that, although not measured under physiological conditions, it is unlikely that the binding in vivo between type II collagen and proteoglycan is appreciably stronger than that between type I collagen and proteoglycan.

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Substitution of aspartic acid for glycine at position 310 in type II collagen produces achondrogenesis II, and substitution of serine at position 805 produces hypochondrogenesis: analysis of genotype-phenotype relationships

Biochemical Journal ◽

10.1042/bj3070823 ◽

1995 ◽

Vol 307 (3) ◽

pp. 823-830 ◽

Cited By ~ 17

Author(s):

J Bonaventure ◽

L Cohen-Solal ◽

P Ritvaniemi ◽

L Van Maldergem ◽

N Kadhom ◽

...

Keyword(s):

Type I Collagen ◽

Denaturing Gradient Gel Electrophoresis ◽

Type Ii Collagen ◽

Terminal Region ◽

Collagen Molecule ◽

Type I ◽

Type Ii ◽

Single Base ◽

Glycine Substitution ◽

Achondrogenesis Type

Two different mutations were found in two unrelated probands with lethal chondrodysplasias, one with achondrogenesis type II and the other with the less severe phenotype of hypochondrogenesis. The mutations in the COL2A1 gene were identified by denaturing gradient gel electrophoresis analysis of genomic DNA followed by dideoxynucleotide sequencing and restriction site analysis. The proband with achondrogenesis type II had a heterozygous single-base mutation that substituted aspartate for glycine at position 310 of the alpha 1(II) chain of type II procollagen. The proband with hypochondrogenesis had a heterozygous single-base mutation that substituted serine for glycine at position 805. Type II collagen extracted from cartilage from the probands demonstrated the presence of type I collagen and a delayed electrophoretic mobility, indicating post-translational overmodifications. Analysis of CNBr peptides showed that, in proband 1, the entire peptides were overmodified. Examination of chondrocytes cultured in agarose or alginate indicated that there was a delayed secretion of type II procollagen. In addition, type II collagen synthesized by cartilage fragments from the probands demonstrated a decreased thermal stability. The melting temperature of the type II collagen containing the aspartate-for-glycine substitution was reduced by 4 degrees C, and that of the collagen containing the serine-for-glycine substitution was reduced by 2 degrees C. Electron microscopy of the extracellular matrix from the chondrocyte cultures showed a decreased density of matrix and the presence of unusually short and thin fibrils. Our results indicate that glycine substitutions in the N-terminal region of the type II collagen molecule can produce more severe phenotypes than mutations in the C-terminal region. The aspartate-for-glycine substitution at position 310, which was associated with defective secretion and a probable increased degradation of collagen, is the most destabilizing mutation yet reported in type II procollagen.

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