Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- Osteolysis

Wu, Chuanlong; Liu, Xuqiang; Sun, Ruixin; Qin, Yunhao; Liu, Zhiqing; Yang, Shengbing; Tang, Tingting; Zhu, Zhenan; Yu, Degang; Li, Fengxiang

doi:10.3389/fphar.2018.01291

Cited by 6 publications

(5 citation statements)

References 42 publications

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“…ZYX can repair the vascular endothelial injury by regulating endothelial cell exocytosis to reorganize the local actin network ( 65 ). Previous studies have shown that SLC4A2-mediated osteoclast anion exchange affects bone resorption by regulating pHi ( 66 , 67 ). PPP1R15A promotes apoptosis, alleviating stress-induced osteoblast damage ( 68 , 69 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic analysis and validation of diagnostic marker genes in patients with osteoporosis

Wang¹,

Pei²,

Hao³

et al. 2022

Front. Immunol.

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BackgroundsAs a systemic skeletal dysfunction, osteoporosis (OP) is characterized by low bone mass and bone microarchitectural damage. The global incidences of OP are high.MethodsData were retrieved from databases like Gene Expression Omnibus (GEO), GeneCards, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Gene Expression Profiling Interactive Analysis (GEPIA2), and other databases. R software (version 4.1.1) was used to identify differentially expressed genes (DEGs) and perform functional analysis. The Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression and random forest algorithm were combined and used for screening diagnostic markers for OP. The diagnostic value was assessed by the receiver operating characteristic (ROC) curve. Molecular signature subtypes were identified using a consensus clustering approach, and prognostic analysis was performed. The level of immune cell infiltration was assessed by the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm. The hub gene was identified using the CytoHubba algorithm. Real-time fluorescence quantitative PCR (RT-qPCR) was performed on the plasma of osteoporosis patients and control samples. The interaction network was constructed between the hub genes and miRNAs, transcription factors, RNA binding proteins, and drugs.ResultsA total of 40 DEGs, eight OP-related differential genes, six OP diagnostic marker genes, four OP key diagnostic marker genes, and ten hub genes (TNF, RARRES2, FLNA, STXBP2, EGR2, MAP4K2, NFKBIA, JUNB, SPI1, CTSD) were identified. RT-qPCR results revealed a total of eight genes had significant differential expression between osteoporosis patients and control samples. Enrichment analysis showed these genes were mainly related to MAPK signaling pathways, TNF signaling pathway, apoptosis, and Salmonella infection. RT-qPCR also revealed that the MAPK signaling pathway (p38, TRAF6) and NF-kappa B signaling pathway (c-FLIP, MIP1β) were significantly different between osteoporosis patients and control samples. The analysis of immune cell infiltration revealed that monocytes, activated CD4 memory T cells, and memory and naïve B cells may be related to the occurrence and development of OP.ConclusionsWe identified six novel OP diagnostic marker genes and ten OP-hub genes. These genes can be used to improve the prognostic of OP and to identify potential relationships between the immune microenvironment and OP. Our research will provide insights into the potential therapeutic targets and pathogenesis of osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Prognostic analysis and validation of diagnostic marker genes in patients with osteoporosis

Wang¹,

Pei²,

Hao³

et al. 2022

Front. Immunol.

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“…As SLC4A2 plays a role in forming the actin rings of osteoclasts, it is considered a pathogenic gene to treat periprosthesis osteolysis. DIDS, which blocks SLC4A2 expression, has a positive effect on the reduction of the region that resorbs the bone, providing plausible evidence for its role in the therapeutic strategy of osteoclastic-associated osteolytic diseases [122].…”

Section: Slc4a2mentioning

confidence: 98%

Potential Theranostic Roles of SLC4 Molecules in Human Diseases

Zhong,

Dong,

Ruan

et al. 2023

IJMS

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The solute carrier family 4 (SLC4) is an important protein responsible for the transport of various ions across the cell membrane and mediating diverse physiological functions, such as the ion transporting function, protein-to-protein interactions, and molecular transduction. The deficiencies in SLC4 molecules may cause multisystem disease involving, particularly, the respiratory system, digestive, urinary, endocrine, hematopoietic, and central nervous systems. Currently, there are no effective strategies to treat these diseases. SLC4 proteins are also found to contribute to tumorigenesis and development, and some of them are regarded as therapeutic targets in quite a few clinical trials. This indicates that SLC4 proteins have potential clinical prospects. In view of their functional characteristics, there is a critical need to review the specific functions of bicarbonate transporters, their related diseases, and the involved pathological mechanisms. We summarize the diseases caused by the mutations in SLC4 family genes and briefly introduce the clinical manifestations of these diseases as well as the current treatment strategies. Additionally, we illustrate their roles in terms of the physiology and pathogenesis that has been currently researched, which might be the future therapeutic and diagnostic targets of diseases and a new direction for drug research and development.

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“…A future challenge will be deciphering the exact contribution of each SLC4A2 variant in OCs as well as exploiting this transporter family for therapeutic targeting. A recent study demonstrating that the anion exchange inhibitor 4, 4 -diisothiocyano-2,2 -stilbenedisulfonic acid (DIDS) is capable of suppressing OC activity in a mouse model of wear-particle-induced osteolysis (Wu et al, 2018) lends 'proof of principal' toward this.…”

Section: Slc4a2mentioning

confidence: 99%

Membrane Transport Proteins in Osteoclasts: The Ins and Outs

Ribet

Pavlos

2021

Front. Cell Dev. Biol.

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During bone resorption, the osteoclast must sustain an extraordinarily low pH environment, withstand immense ionic pressures, and coordinate nutrient and waste exchange across its membrane to sustain its unique structural and functional polarity. To achieve this, osteoclasts are equipped with an elaborate set of membrane transport proteins (pumps, transporters and channels) that serve as molecular ‘gatekeepers’ to regulate the bilateral exchange of ions, amino acids, metabolites and macromolecules across the ruffled border and basolateral domains. Whereas the importance of the vacuolar-ATPase proton pump and chloride voltage-gated channel 7 in osteoclasts has long been established, comparatively little is known about the contributions of other membrane transport proteins, including those categorized as secondary active transporters. In this Special Issue review, we provide a contemporary update on the ‘ins and outs’ of membrane transport proteins implicated in osteoclast differentiation, function and bone homeostasis and discuss their therapeutic potential for the treatment of metabolic bone diseases.

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Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- Osteolysis

Cited by 6 publications

References 42 publications

Prognostic analysis and validation of diagnostic marker genes in patients with osteoporosis

Prognostic analysis and validation of diagnostic marker genes in patients with osteoporosis

Potential Theranostic Roles of SLC4 Molecules in Human Diseases

Membrane Transport Proteins in Osteoclasts: The Ins and Outs

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