Mitochondrial quality control and its role in osteoporosis

Cao, Yan; Shi, Yao; Yuan, Ling‐Qing; Lv, Donghui; Sun, Binyong; Wang, Jiayu; Liu, Xiyan; An, Fangyu

doi:10.3389/fendo.2023.1077058

Cited by 26 publications

(18 citation statements)

References 86 publications

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“…In an effort to further explore the cause in the aforementioned results, we evaluated key molecules of oxidative stress and energy metabolism, cellular processes that affect bone health and bone-related diseases such as osteoporosis [16,[49][50][51][52][53][54]. We first examined the gene and/or protein expression levels of Pgc1a and Tfam, as important factors of mitochondrial biogenesis in bone cells [24].…”

Section: Discussionmentioning

confidence: 99%

Defining the most potent osteoinductive culture conditions for MC3T3-E1 cells reveals no implication of oxidative stress or energy metabolism

Semicheva,

Ersoy,

Vasilaki

et al. 2024

Preprint

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MC3T3-E1 preosteoblastic cell line is widely utilised as a reliable in vitro system to assess bone formation. However, the experimental growth conditions for these cells hugely diverge and, particularly, the osteogenic medium (OSM) composition varies in research studies. Therefore, we aimed to define the ideal culture conditions for MC3T3-E1 subclone 4 cells with regards to mineralization capacity and explore if oxidative stress or cellular metabolism processes are implicated. Cells were treated with 9 different combinations of long-lasting ascorbate (Asc) and beta-glycerophosphate (betaGP) and osteogenesis/calcification were evaluated at 3 different time-points by qPCR, Western blotting and bone nodule staining. Key molecules of oxidative and metabolic pathways were also assessed. It was found that sufficient mineral deposition was achieved only in 150 ug.mL-1/2mM Asc/betaGP combination at 21d in OSM and this was supported by Runx2, Alpl, Bglap and Col1a1 expression levels increase. NOX2 and SOD2 as well as PGC1alpha and Tfam were also monitored as indicators of redox and metabolic processes, respectively, where no differences were observed. Elevation in OCN protein levels and ALP activity showed that mineralisation comes as a result of these differences. This work defines the most appropriate culture conditions for MC3T3-E1 cells and could be used by other research laboratories in this field.

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Section: Discussionmentioning

confidence: 99%

Defining the most potent osteoinductive culture conditions for MC3T3-E1 cells reveals no implication of oxidative stress or energy metabolism

Semicheva,

Ersoy,

Vasilaki

et al. 2024

Preprint

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“…The clinical data of all patients were obtained from the Gene Expression Omnibus (GEO) database ( https://www.ncbi.nlm.nih.gov/geo/ ). According to the following criteria: ( Yan et al, 2023 ) Disease name: Osteoporosis ( Langdahl, 2020 ); Organism type: Homo sapiens ( Guo et al, 2021 ). Sample source: blood sample ( Guo et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…Osteoporosis (OP) is a systemic bone disease and the most common metabolic bone disease ( Langdahl, 2020 ; Yan et al, 2023 ). They can be divided into two categories: primary and secondary.…”

Section: Introductionmentioning

confidence: 99%

“…However, it can also be induced under certain pathological or physiological conditions, thereby degrading healthy mitochondria and ultimately promoting the development of many diseases ( Fang et al, 2019 ; Xu et al, 2020 ; Zhang et al, 2021 ). In addition, mitophagy has shown excellent medical application value in many chronic diseases and is considered to be an important target for the treatment of chronic diseases ( Yan et al, 2023 ). Increasing evidence shows that abnormal mitochondrial autophagy can disrupt the balance of bone metabolism and plays a key role in bone metabolism disorders ( Wang et al, 2017 ; Naik et al, 2019 ; Wang S. et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Identification of mitophagy-related biomarkers in human osteoporosis based on a machine learning model

Su,

Yu,

et al. 2024

Front. Physiol.

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Background: Osteoporosis (OP) is a chronic bone metabolic disease and a serious global public health problem. Several studies have shown that mitophagy plays an important role in bone metabolism disorders; however, its role in osteoporosis remains unclear.Methods: The Gene Expression Omnibus (GEO) database was used to download GSE56815, a dataset containing low and high BMD, and differentially expressed genes (DEGs) were analyzed. Mitochondrial autophagy-related genes (MRG) were downloaded from the existing literature, and highly correlated MRG were screened by bioinformatics methods. The results from both were taken as differentially expressed (DE)-MRG, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. Protein-protein interaction network (PPI) analysis, support vector machine recursive feature elimination (SVM-RFE), and Boruta method were used to identify DE-MRG. A receiver operating characteristic curve (ROC) was drawn, a nomogram model was constructed to determine its diagnostic value, and a variety of bioinformatics methods were used to verify the relationship between these related genes and OP, including GO and KEGG analysis, IP pathway analysis, and single-sample Gene Set Enrichment Analysis (ssGSEA). In addition, a hub gene-related network was constructed and potential drugs for the treatment of OP were predicted. Finally, the specific genes were verified by real-time quantitative polymerase chain reaction (RT-qPCR).Results: In total, 548 DEGs were identified in the GSE56815 dataset. The weighted gene co-expression network analysis(WGCNA) identified 2291 key module genes, and 91 DE-MRG were obtained by combining the two. The PPI network revealed that the target gene for AKT1 interacted with most proteins. Three MRG (NELFB, SFSWAP, and MAP3K3) were identified as hub genes, with areas under the curve (AUC) 0.75, 0.71, and 0.70, respectively. The nomogram model has high diagnostic value. GO and KEGG analysis showed that ribosome pathway and cellular ribosome pathway may be the pathways regulating the progression of OP. IPA showed that MAP3K3 was associated with six pathways, including GNRH Signaling. The ssGSEA indicated that NELFB was highly correlated with iDCs (cor = −0.390, p < 0.001). The regulatory network showed a complex relationship between miRNA, transcription factor(TF) and hub genes. In addition, 4 drugs such as vinclozolin were predicted to be potential therapeutic drugs for OP. In RT-qPCR verification, the hub gene NELFB was consistent with the results of bioinformatics analysis.Conclusion: Mitophagy plays an important role in the development of osteoporosis. The identification of three mitophagy-related genes may contribute to the early diagnosis, mechanism research and treatment of OP.

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“…Osteoporosis is a chronic metabolic bone disease mainly caused by an imbalance in osteoblast and osteoclast activity [ 98 ]. The elderly population and postmenopausal women are at high risk of osteoporosis.…”

Section: Hypoxic Bone-on-a-chip Modelsmentioning

confidence: 99%

Construction of Bone Hypoxic Microenvironment Based on Bone-on-a-Chip Platforms

Zhao

Yang

et al. 2023

IJMS

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The normal physiological activities and functions of bone cells cannot be separated from the balance of the oxygenation level, and the physiological activities of bone cells are different under different oxygenation levels. At present, in vitro cell cultures are generally performed in a normoxic environment, and the partial pressure of oxygen of a conventional incubator is generally set at 141 mmHg (18.6%, close to the 20.1% oxygen in ambient air). This value is higher than the mean value of the oxygen partial pressure in human bone tissue. Additionally, the further away from the endosteal sinusoids, the lower the oxygen content. It follows that the construction of a hypoxic microenvironment is the key point of in vitro experimental investigation. However, current methods of cellular research cannot realize precise control of oxygenation levels at the microscale, and the development of microfluidic platforms can overcome the inherent limitations of these methods. In addition to discussing the characteristics of the hypoxic microenvironment in bone tissue, this review will discuss various methods of constructing oxygen gradients in vitro and measuring oxygen tension from the microscale based on microfluidic technology. This integration of advantages and disadvantages to perfect the experimental study will help us to study the physiological responses of cells under more physiological-relevant conditions and provide a new strategy for future research on various in vitro cell biomedicines.

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Mitochondrial quality control and its role in osteoporosis

Cited by 26 publications

References 86 publications

Defining the most potent osteoinductive culture conditions for MC3T3-E1 cells reveals no implication of oxidative stress or energy metabolism

Defining the most potent osteoinductive culture conditions for MC3T3-E1 cells reveals no implication of oxidative stress or energy metabolism

Identification of mitophagy-related biomarkers in human osteoporosis based on a machine learning model

Construction of Bone Hypoxic Microenvironment Based on Bone-on-a-Chip Platforms

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