Low‐dose γ‐radiation inhibits IL‐1β‐induced dedifferentiation and inflammation of articular chondrocytes via blockage of catenin signaling

Hong, Eun-Hee; Song, Jie‐Young; Lee, Su‐Jae; Park, In-Chul; Um, Hong‐Duck; Park, Jong Kuk; Lee, Kee-Ho; Nam, Sang Yong; Hwang, Sang‐Gu

doi:10.1002/iub.1248

Cited by 21 publications

(19 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the context of inflammation, high dose radiation can have unwanted adverse effect on normal cells during cancer therapy. Whereas, recently Hong et al reported that LDR successfully inhibited the inflammation by blockage of catenin signaling pathway in chondrocytes without causing any side effects at doses below than 1 cGy 37 .…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation

Kim

Seong

et al. 2015

Sci Rep

Self Cite

View full text Add to dashboard Cite

Recently low dose irradiation has gained attention in the field of radiotherapy. For lack of understanding of the molecular consequences of low dose irradiation, there is much doubt concerning its risks on human beings. In this article, we report that low dose irradiation is capable of blocking the oncogenic KRAS-induced malignant transformation. To address this hypothesis, we showed that low dose irradiation, at doses of 0.1 Gray (Gy); predominantly provide defensive response against oncogenic KRAS -induced malignant transformation in human cells through the induction of antioxidants without causing cell death and acts as a critical regulator for the attenuation of reactive oxygen species (ROS). Importantly, we elucidated that knockdown of antioxidants significantly enhanced ROS generation, invasive and migratory properties and abnormal acini formation in KRAS transformed normal as well as cancer cells. Taken together, this study demonstrates that low dose irradiation reduces the KRAS induced malignant cellular transformation through diminution of ROS. This interesting phenomenon illuminates the beneficial effects of low dose irradiation, suggesting one of contributory mechanisms for reducing the oncogene induced carcinogenesis that intensify the potential use of low dose irradiation as a standard regimen.

show abstract

Section: Discussionmentioning

confidence: 99%

Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation

Kim

Seong

et al. 2015

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…By demonstrating the reversibility of human b cell dedifferentiation, we propose that MSCs administration can be a potential approach to hinder or reverse this process. Furthermore, cell dedifferentiation has been observed in a number of cells such as neural cells [58], chondrocytes [59] and cancer cells [60,61]. In all cases, local inflammation plays a key role in inducing the dedifferentiation of these cells.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells ameliorate β cell dysfunction of human type 2 diabetic islets by reversing β cell dedifferentiation

Wang

Liu²,

Liang³

et al. 2020

EBioMedicine

View full text Add to dashboard Cite

A B S T R A C TBackground: A physiological hallmark of patients with type 2 diabetes mellitus (T2DM) is b cell dysfunction.Despite adequate treatment, it is an irreversible process that follows disease progression. Therefore, the development of novel therapies that restore b cell function is of utmost importance.Methods: This study aims to unveil the mechanistic action of mesenchymal stem cells (MSCs) by investigating its impact on isolated human T2DM islets ex vivo and in vivo.Findings: We propose that MSCs can attenuate b cell dysfunction by reversing b cell dedifferentiation in an IL-1Ra-mediated manner. In response to the elevated expression of proinflammatory cytokines in human T2DM islet cells, we observed that MSCs was activated to secret IL-1R antagonist (IL-1Ra) which acted on the inflammed islets and reversed b cell dedifferentiation, suggesting a crosstalk between MSCs and human T2DM islets. The co-transplantation of MSCs with human T2DM islets in diabetic SCID mice and intravenous infusion of MSCs in db/db mice revealed the reversal of b cell dedifferentiation and improved glycaemic control in the latter. Interpretation: This evidence highlights the potential of MSCs in future cell-based therapies regarding the amelioration of b cell dysfunction.

show abstract

“…A recent study showed that radiation-induced production of pro-inflammatory cytokines and induction of ERK/MAPK and JNK/SAPK pathways is linked to the p53 status of the cells (98). Chondrocytes have been shown to also produce both inflammatory mediators and receptors that may drive to cartilage pathogenesis by connecting catenin-related cascade to IL-1b upstream and Sox-9 and NF-jB downstream (97,99). In addition, PGC1a and FoxO3a limit oxidative stress by controlling AMPactivated protein kinase (AMPK) activity to block procatabolic responses in chondrocytes (100).…”

Section: Inflammation Of Cartilage After Irradiationmentioning

confidence: 97%

Impact of Therapeutic Irradiation on Healthy Articular Cartilage

Saintigny¹,

Cruet-Hennequart²,

Hamdi³

et al. 2015

Radiation Research

View full text Add to dashboard Cite

Radiation-induced complications in bone and cartilage are of increasing concern due to potential long-term effects in cancer survivors. Healthy articular cartilage may be exposed to radiation during either chondrosarcoma treatment or in-field radiotherapy of tumors located in close proximity to articulation. Cartilage exposed to radiation undergoes bone differentiation and senescence, which can lead to painful and disabling sequelae that can impair patient quality of life. An understanding of the biological processes involved in healthy cartilage response to radiotherapy may not only optimize the delivery of therapeutic radiation but also reduce the risk of long-term sequelae in irradiated cartilage. Over the last few decades, radiobiology studies have focused primarily on signaling and repair of DNA damage pathways induced by ionizing radiation in immortalized cells under conditions dramatically different from human homeostasis. This research needs to be continued and broadened, since the range of normal tissue responses to radiation exposure is still not fully understood, despite being recognized as the major limiting factor in the rupture of tissue homeostasis after radiotherapy. Human articular cartilage is an avascular tissue with low intracellular oxygen levels and is comprised of a single cell lineage of chondrocytes embedded in a highly dense and structured extracellular matrix. These relatively unique features may impact inherent cell radiation sensitivity and suggests that canonical cell responses to ionizing radiation may not be applicable to articular cartilage. Despite the number of studies in this field, radiation-induced modifications of chondrocyte proteome remain unclear because of the dramatic variability in reported experimental conditions. In this review, we propose to introduce cartilage tissue physiology and microenvironment concepts, and then present a comprehensive synthesis of cartilage radiation biology.

show abstract

Low‐dose γ‐radiation inhibits IL‐1β‐induced dedifferentiation and inflammation of articular chondrocytes via blockage of catenin signaling

Cited by 21 publications

References 18 publications

Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation

Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation

Mesenchymal stem cells ameliorate β cell dysfunction of human type 2 diabetic islets by reversing β cell dedifferentiation

Impact of Therapeutic Irradiation on Healthy Articular Cartilage

Contact Info

Product

Resources

About