Type VI collagen deficiency induces osteopenia with distortion of osteoblastic cell morphology

Izu, Yayoi; Ezura, Yoichi; Mizoguchi, Fumitaka; Kawamata, Aya; Nakamoto, Tetsuya; Nakashima, Kazuhisa; Hayata, Tadayoshi; Hemmi, Hiroaki; Bonaldo, Paolo; Noda, Masaki

doi:10.1016/j.tice.2011.08.002

Cited by 23 publications

(30 citation statements)

References 22 publications

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“…With regard to bone, Col6a1 −/− mice display abnormalities in the morphology of the knee trabecular bone structure, as revealed by the lower bone volume and connective tissue density, the reduced trabecular number and thickness, and the higher structure model index (a quantitative measure of the trabecular shape) and trabecular separation compared with those of wild-type mice (Christensen et al, 2012). Similar findings have been demonstrated in the femora of Col6a1 −/− mice, which contain osteoblasts with distorted shapes and disorganized arrangement of the surrounding collagens (Izu et al, 2012). Interestingly, a reduced amount of ColVI is reported in the ECM of human osteoporotic bones (Bailey et al, 1993).…”

Section: Bone and Cartilagesupporting

confidence: 58%

Collagen VI at a glance

Cescon

Gattazzo

Chen

et al. 2015

Journal of Cell Science

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286

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Collagen VI represents a remarkable extracellular matrix molecule, and in the past few years, studies of this molecule have revealed its involvement in a wide range of tissues and pathological conditions. In addition to its complex multi-step pathway of biosynthesis and assembly that leads to the formation of a characteristic and distinctive network of beaded microfilaments in the extracellular matrix, collagen VI exerts several key roles in different tissues. These range from unique biomechanical roles to cytoprotective functions in different cells, including myofibers, chondrocytes, neurons, fibroblasts and cardiomyocytes. Indeed, collagen VI has been shown to exert a surprisingly broad range of cytoprotective effects, which include counteracting apoptosis and oxidative damage, favoring tumor growth and progression, regulating autophagy and cell differentiation, and even contributing to the maintenance of stemness. In this Cell Science at a Glance article and the accompanying poster, we present the current knowledge of collagen VI, and in particular, discuss its relevance in stemness and in preserving the mechanical properties of tissues, as well as its links with human disorders.

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Section: Bone and Cartilagesupporting

confidence: 58%

Collagen VI at a glance

Cescon

Gattazzo

Chen

et al. 2015

Journal of Cell Science

Self Cite

285

286

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“…A, B ). This is of interest because both collagens have been shown to be essential for osteoblast function . Accordingly, we found that immunoblockade of either collagen in BGF reduced transcription of BMP2 by OEhMSCs without affecting their attachment.…”

Section: Discussionmentioning

confidence: 73%

“…A ). This is significant because types VI and XII collagen localize to regenerating bone tissue, and deficits of collagen VI and XII in mice cause osteoblast abnormalities . It is, therefore, possible that type VI and XII collagen in BGF may induce expression of BMP2 by OEhMSCs, accounting for some of the beneficial effects of BGF in bone healing.…”

Section: Resultsmentioning

confidence: 99%

Bone Regeneration With Osteogenically Enhanced Mesenchymal Stem Cells and Their Extracellular Matrix Proteins

Clough

McCarley

Krause

et al. 2014

Journal of Bone and Mineral Research

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Although bone has remarkable regenerative capacity, about 10% of long bone fractures and 25–40% of vertebral fusion procedures fail to heal. In such instances, a scaffold is employed to bridge the lesion and accommodate osteoprogenitors. Although synthetic bone scaffolds mimic some of the characteristics of bone matrix, their effectiveness can vary due to biological incompatibility. Herein, we demonstrate that a composite prepared with osteogenically enhanced mesenchymal stem cells (OEhMSCs) and their extracellular matrix (ECM) has an unprecedented capacity for the repair of critical-sized defects of murine femora. Furthermore, OEhMSCs do not cause lymphocyte activation and ECM/OEhMSC composites retain their in vivo efficacy after cryopreservation. We finally show that attachment to the ECM by OEhMSCs stimulates the production of osteogenic and angiogenic factors. These data demonstrate that composites of OEhMSCs and their ECM could be utilized in the place of autologous bone graft for complex orthopedic reconstructions.

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“…The CLOCK gene deregulation, we also confirmed at the protein level in Col6a1 −/− mice, suggests a previously unreported relationship between circadian rhythms, the molecular clock and myopathy. The Col6a1 −/− model shows both muscle and osteotendinous junction damage (Izu et al, 2011(Izu et al, , 2012, reflecting defective costamerogenesis and altered mechanotransduction (De Palma et al, 2013). Specific activation of both myocardinrelated transcription factors (MRTFs) and ternary complex factors (TCFs), whose targets are regulators of cytoskeleton dynamics and mechanosensing, have potential to reset the molecular clock through regulation of PER1, PER2, BMAL1 and other CLOCK genes (Esnault et al, 2014).…”

Section: Col6a1mentioning

confidence: 99%

Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy

Scotton

Bovolenta

Schwartz

et al. 2016

Journal of Cell Science

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Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1 −/− ) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between collagen VI defects and these metabolic circuits remains unknown. To unravel the expression profiling perturbation in muscles with collagen VI myopathies, we performed a deep RNA profiling in both Col6a1 −/− mice and patients with collagen VI pathology. The interactome map identified common pathways suggesting a previously undetected connection between circadian genes and collagen VI pathology. Intriguingly, Bmal1 −/− (also known as Arntl) mice, a well-characterized model displaying arrhythmic circadian rhythms, showed profound deregulation of the collagen VI pathway and of autophagy-related genes. The involvement of circadian rhythms in collagen VI myopathies is new and links autophagy and mitochondrial abnormalities. It also opens new avenues for therapies of hereditary myopathies to modulate the molecular clock or potential gene-environment interactions that might modify muscle damage pathogenesis.

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Type VI collagen deficiency induces osteopenia with distortion of osteoblastic cell morphology

Cited by 23 publications

References 22 publications

Collagen VI at a glance

Collagen VI at a glance

Bone Regeneration With Osteogenically Enhanced Mesenchymal Stem Cells and Their Extracellular Matrix Proteins

Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy

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