Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium

Komori, Taishi; Ono, M.; Hara, Emilio Satoshi; Ueda, Junji; Nguyen, Ha Thi Thu; Yonezawa, Tomoko; Maeba, Takahiro; Kimura‐Ono, Aya; Takarada, Takeshi; Momota, Ryusuke; Maekawa, Kenji; Kuboki, Takuo; Oohashi, Toshitaka

doi:10.1038/s41598-018-21000-0

Cited by 22 publications

(34 citation statements)

References 38 publications

(32 reference statements)

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“…Thus, inappropriate expression of keratins appears as a general trait associated to LUAD aggressiveness, whether through perturbation of the differentiation status of adenocarcinoma cells or by regulation of epithelial progenitor/stem cells, as recently shown for keratin 14 [ 18 ]. The collagen gene COL4A6 was shown to be a LUAD protective factor, as possibly related to its regulatory role on cytokeratin expression and epithelial differentiation [ 25 ]. COL7A1 acted as a tumor progression determinant, possibly through its association to cancer stem cells development [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Distinct lung cancer subtypes associate to distinct drivers of tumor progression

et al. 2018

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The main non–small-cell lung cancer (NSCLC) histopathological subtypes are lung adenocarcinomas (LUAD) and lung squamous cell carcinomas (LUSC). To identify candidate progression determinants of NSCLC subtypes, we explored the transcriptomic signatures of LUAD versus LUSC. We then investigated the prognostic impact of the identified tumor-associated determinants. This was done utilizing DNA microarray data from 2,437 NSCLC patients. An independent analysis of a case series of 994 NSCLC was conducted by next-generation sequencing, together with gene expression profiling from GEO (https://www.ncbi.nlm.nih.gov/geo/).This work led us to identify 69 distinct tumor prognostic determinants, which impact on LUAD or LUSC clinical outcome. These included key drivers of tumor growth and cell cycle, transcription factors and metabolic determinants. Such disease determinants appeared vastly different in LUAD versus LUSC, and often had opposite impact on clinical outcome. These findings indicate that distinct tumor progression pathways are at work in the two NSCLC subtypes. Notably, most prognostic determinants would go inappropriately assessed or even undetected when globally investigating unselected NSCLC. Hence, differential consideration for NSCLC subtypes should be taken into account in current clinical evaluation procedures for lung cancer.

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Section: Discussionmentioning

confidence: 99%

Distinct lung cancer subtypes associate to distinct drivers of tumor progression

et al. 2018

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“…For immunohistochemical (IHC) analysis, frozen sections were prepared by using the Kawamoto’s film method, according to a previous report [ 37 ]. Briefly, samples fixed with 4% PFA were freeze-embedded in super cryoembedding medium (SECTION-LAB Co., Ltd., Hiroshima, Japan) and cut into widths of 5 μm with a tungsten carbide blade using an adhesive film.…”

Section: Methodsmentioning

confidence: 99%

BMP-2/β-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model

Mikai

Ono

Tosa

et al. 2020

IJMS

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Medication-related osteonecrosis of the jaw (MRONJ) is a severe pathological condition associated mainly with the long-term administration of bone resorption inhibitors, which are known to induce suppression of osteoclast activity and bone remodeling. Bone Morphogenetic Protein (BMP)-2 is known to be a strong inducer of bone remodeling, by directly regulating osteoblast differentiation and osteoclast activity. This study aimed to evaluate the effects of BMP-2 adsorbed onto beta-tricalcium phosphate (β-TCP), which is an osteoinductive bioceramic material and allows space retention, on the prevention and treatment of MRONJ in mice. Tooth extraction was performed after 3 weeks of zoledronate (ZA) and cyclophosphamide (CY) administration. For prevention studies, BMP-2/β-TCP was transplanted immediately after tooth extraction, and the mice were administered ZA and CY for an additional 4 weeks. The results showed that while the tooth extraction socket was mainly filled with a sparse tissue in the control group, bone formation was observed at the apex of the tooth extraction socket and was filled with a dense connective tissue rich in cellular components in the BMP-2/β-TCP transplanted group. For treatment studies, BMP-2/β-TCP was transplanted 2 weeks after tooth extraction, and bone formation was followed up for the subsequent 4 weeks under ZA and CY suspension. The results showed that although the tooth extraction socket was mainly filled with soft tissue in the control group, transplantation of BMP-2/β-TCP could significantly accelerate bone formation, as shown by immunohistochemical analysis for osteopontin, and reduce the bone necrosis in tooth extraction sockets. These data suggest that the combination of BMP-2/β-TCP could become a suitable therapy for the management of MRONJ.

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“…Analysis of bone volume/tissue volume (BV/TV) and BMD was made at an area within 1 mm above and below the defect. Decalcified mouse samples were sectioned and stained with H&E. For observation of osteoblasts in Col1a1 (2.3)‐GFP mice, frozen sections were prepared according to a previous report …”

Section: Methodsmentioning

confidence: 99%

Bone Marrow Cells Inhibit BMP-2-Induced Osteoblast Activity in the Marrow Environment

Ono

Oida

Hara

et al. 2018

Journal of Bone and Mineral Research

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Bone morphogenetic protein 2 (BMP-2) is widely known as a potent growth factor that promotes bone formation. However, an increasing number of studies have demonstrated side effects of BMP-2 therapy. A deeper understanding of the effect of BMP-2 on cells other than those involved directly in bone remodeling is of fundamental importance to promote a more effective delivery of BMP-2 to patients. In this study, we aimed to investigate the effect of BMP-2 in the marrow environment. First, BMP-2 adsorbed onto titanium implants was delivered at the tooth extraction socket (marrow-absent site) or in the mandible marrow of beagle dogs. BMP-2 could induce marked bone formation around the implant at the tooth extraction socket. Surprisingly, however, no bone formation was observed in the BMP-2-coated titanium implants inserted in the mandible marrow. In C57BL/6 mice, BMP-2 adsorbed in freeze-dried collagen pellets could induce bone formation in marrow-absent calvarial bone. However, similar to the canine model, BMP-2 could not induce bone formation in the femur marrow. Analysis of osteoblast differentiation using Col1a1(2.3)-GFP transgenic mice revealed a scarce number of osteoblasts in BMP-2-treated femurs, whereas in the control group, osteoblasts were abundant. Ablation of femur marrow recovered the BMP-2 ability to induce bone formation. In vitro experiments analyzing luciferase activity of C2C12 cells with the BMP-responsive element and alkaline phosphatase activity of MC3T3-E1 osteoblasts further revealed that bone marrow cells inhibit the BMP-2 effect on osteoblasts by direct cell-cell contact. Collectively, these results showed that the effect of BMP-2 in inducing bone formation is remarkably repressed by marrow cells via direct cell-cell contact with osteoblasts; this opens new perspectives on the clarification of the side-effects associated with BMP-2 application.

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Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium

Cited by 22 publications

References 38 publications

Distinct lung cancer subtypes associate to distinct drivers of tumor progression

Distinct lung cancer subtypes associate to distinct drivers of tumor progression

BMP-2/β-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model

Bone Marrow Cells Inhibit BMP-2-Induced Osteoblast Activity in the Marrow Environment

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