The Role of Autophagy and Mitophagy in Bone Metabolic Disorders

Wang, Shuai; Deng, Zhong‐Liang; Ma, Yuanfang; Jin, Jiewen; Qi, Fangjie; Li, Shuxian; Liu, Chang; Lyu, Feng‐Juan; Zheng, Qiujian

doi:10.7150/ijbs.46627

Cited by 152 publications

(100 citation statements)

References 158 publications

(196 reference statements)

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“…The top 60 DE lncRNA-targeted mRNAs are shown in Supplementary Table 1 , including forkhead box O3 (FOXO3), signal-regulatory protein beta 1 (SIRPB1), interleukin 1 receptor type I (IL1R1), etc. FOXO3 has been reported to be important in the control of ROS levels in bone metabolic disorders via the activation of autophagy ( Wang et al, 2020 ), while another member of the FOXO family, FOXO1, has been indicated in SAPHO syndrome ( Berthelot et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

Integrative Analysis of lncRNA-mRNA Profile Reveals Potential Predictors for SAPHO Syndrome

Sun

et al. 2021

Front. Genet.

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Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is known as a rare disease characterized by inflammatory lesions on bones and skin. Polymorphism of clinical manifestation and lack of molecular biomarkers have both limited its diagnosis. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of long noncoding RNA (lncRNA)-messenger RNA (mRNA) profile in patients with SAPHO syndrome and healthy controls. A total of 4,419 differentially expressed (DE) mRNAs and 2,713 lncRNAs were identified (p < 0.05, fold change > 2) and a coexpression network was constructed to further investigate their regulatory interactions. The DE lncRNAs were predicted to interact with mRNAs in both cis and trans manners. Functional prediction found that the lncRNA-targeted genes may function in SAPHO syndrome by participating in biological process such as adipocytokine signaling pathway, ErbB signaling pathway, FoxO signaling pathway, as well as production and function of miRNAs. The expression levels of three pairs of coexpressed lncRNA-mRNAs were validated by qRT-PCR, and their relative expression levels were consistent with the RNA-seq data. The deregulated RNAs GAS7 and lnc-CLLU1.1-1:2 may serve as potential diagnostic biomarkers, and the combined receiver operating characteristic (ROC) curve of the two showed more reliable diagnostic ability with an AUC value of 0.871 in distinguishing SAPHO patients from healthy controls. In conclusion, this study provides a first insight into long noncoding RNA transcriptome profile changes associated with SAPHO syndrome and inspiration for further investigation on clinical biomarkers and molecular regulators of this inadequately understood clinical entity.

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Section: Resultsmentioning

confidence: 99%

Integrative Analysis of lncRNA-mRNA Profile Reveals Potential Predictors for SAPHO Syndrome

Sun

et al. 2021

Front. Genet.

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“…Autophagy plays an important role in the homeostasis maintenance of chondrocytes for clearing dysfunctional organelles and macromolecules [32,33]. With the degeneration of cartilage, autophagy is inhibited and induces the homeostasis imbalance of chondrocytes, eventually leading to cell death [34,35].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of LSD1 alleviates the IL-1β-induced chondrocyte apoptosis, inflammation and ECM degradation via TRIM32-mediated autophagy

Wei

Liu

et al. 2021

Preprint

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Osteoarthritis (OA) is a common joint disease with characteristics of chronic inflammation and articular cartilage degeneration. It has been proved that LSD1 was up-regulated in OA cartilage tissues, but its role and regulatory mechanism in OA are unclear. Herein, interleukin 1 beta (IL-1β)-treated human chondrocytes was performed as a cell model of OA. Then, LSD1 expression was found that up-regulated in OA cartilage tissues and IL-1β-induced chondrocytes. Knockdown of LSD1 increased cell viability, while decreased apoptosis rate and inflammatory cytokines secretion levels in IL-1β-induced chondrocytes. In addition, knockdown of LSD1 reduced the expression of catabolic proteins (MMP-13 and ADAMTS-5) and enhanced the expression of anabolic proteins (Collagen II and Aggrecan) in chondrocytes after IL-1β stimulation. Moreover, overexpression of TRIM32 repressed chondrocyte viability, while promoted IL-1β-induced chondrocyte apoptosis, inflammation and ECM degradation. The expression of LSD1 and TRIM32 in OA cartilage was positively correlated, and knockdown of LSD1 down-regulated TRIM32 expression of chondrocytes. Our data further indicated that LSD1 regulated autophagy of chondrocytes through modulating TRIM32. Overexpression of TRIM32 reduced the effect of LSD1 knockdown on IL-1β-induced chondrocytes, while activating autophagy by Rapamycin further reversed this reduction. Therefore, our study shows that knockdown of LSD1 inhibited IL-1β-induced chondrocyte apoptosis, inflammation and ECM degradation via TRIM32-mediated autophagy.

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“…Impaired ATP production, caused by a dysfunctional mitochondrial transcription factor A (Tfam) gene, led to increased bone resorption (Miyazaki et al, 2012). Mitophagy and the unfolded protein response (UPR mt ) are important for mitochondrial homeostasis (Fang et al, 2014; Mouchiroud et al, 2013b), whereas their disruption leads to severe bone loss, which is closely associated with impaired mitochondrial function (Wang et al, 2020; Zainabadi, Liu, Caldwell, et al, 2017). Furthermore, in vitro cellular and in vivo animal studies have demonstrated a link between mitochondria‐derived reactive oxygen species (ROS) and osteoporosis (Manolagas, 2010; Treiber et al, 2011; Yang et al, 2014).…”

Section: Molecular Mechanism Of Osteoporosismentioning

confidence: 99%

Role of sirtuins in bone biology: Potential implications for novel therapeutic strategies for osteoporosis

Cheng

Jiang

et al. 2021

Aging Cell

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The decline in bone mass and bone strength and musculoskeletal problems associated with aging constitute a major challenge for affected individuals and the healthcare system globally. Sirtuins 1‐7 (SIRT1‐SIRT7) are a family of nicotinamide adenine dinucleotide‐dependent deacetylases with remarkable abilities to promote longevity and counteract age‐related diseases. Sirtuin knockout and transgenic models have provided novel insights into the function and signaling of these proteins in bone homeostasis. Studies have revealed that sirtuins play a critical role in normal skeletal development and homeostasis through their direct action on bone cells and that their dysregulation might contribute to different bone diseases. Preclinical studies have demonstrated that mice treated with sirtuin agonists show protection against age‐related, postmenopausal, and immobilization‐induced osteoporosis. These findings suggest that sirtuins could be potential targets for the modulation of the imbalance in bone remodeling and treatment of osteoporosis and other bone disorders. The aim of this review was to provide a comprehensive updated review of the current knowledge on sirtuin biology, focusing specifically on their roles in bone homeostasis and osteoporosis, and potential pharmacological interventions targeting sirtuins for the treatment of osteoporosis.

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The Role of Autophagy and Mitophagy in Bone Metabolic Disorders

Cited by 152 publications

References 158 publications

Integrative Analysis of lncRNA-mRNA Profile Reveals Potential Predictors for SAPHO Syndrome

Integrative Analysis of lncRNA-mRNA Profile Reveals Potential Predictors for SAPHO Syndrome

Knockdown of LSD1 alleviates the IL-1β-induced chondrocyte apoptosis, inflammation and ECM degradation via TRIM32-mediated autophagy

Role of sirtuins in bone biology: Potential implications for novel therapeutic strategies for osteoporosis

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