Targeted inhibition of ATP5B gene prevents bone erosion in collagen-induced arthritis by inhibiting osteoclastogenesis

Xu, Yanting; Tan, Huijing; Liu, Kaifei; Wen, Cailing; Pang, Caixia; Liu, Haiqian; Xu, Rui; Li, Qixing; He, Chonghua; Nandakumar, Kutty Selva; Zhou, Chun

doi:10.1016/j.phrs.2021.105458

Cited by 12 publications

(4 citation statements)

References 33 publications

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“…The lipo2000 was mixed with the siRNAs and incubated for 20 min at RT. The serum-containing medium in the six-well plate was removed, before 1.5 ml of serum-free medium containing siRNAs was added and cultured in a 5% CO 2 incubator at 37 • C. The solution was changed after 6 h to a normal medium (Xu et al, 2021).…”

Section: Sirna Knockdownmentioning

confidence: 99%

The Regulatory Role of GBF1 on Osteoclast Activation Through EIF2a Mediated ER Stress and Novel Marker FAM129A Induction

Wen

Zhou

et al. 2021

Front. Cell Dev. Biol.

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Bone-resorbing activities of osteoclasts (OCs) are highly dependent on actin cytoskeleton remodeling, plasma membrane reorganization, and vesicle trafficking pathways, which are partially regulated by ARF-GTPases. In the present study, the functional roles of Golgi brefeldin A resistance factor 1 (GBF1) are proposed. GBF1 is responsible for the activation of the ARFs family and vesicular transport at the endoplasmic reticulum–Golgi interface in different stages of OCs differentiation. In the early stage, GBF1 deficiency impaired OCs differentiation and was accompanied with OCs swelling and reduced formation of mature OCs, indicating that GBF1 participates in osteoclastogenesis. Using siRNA and the specific inhibitor GCA for GBF1 knockdown upregulated endoplasmic reticulum stress-associated signaling molecules, including BiP, p-PERK, p-EIF2α, and FAM129A, and promoted autophagic Beclin1, Atg7, p62, and LC3 axis, leading to apoptosis of OCs. The present data suggest that, by blocking COPI-mediated vesicular trafficking, GBF1 inhibition caused intense stress to the endoplasmic reticulum and excessive autophagy, eventually resulting in the apoptosis of mature OCs and impaired bone resorption function.

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Section: Sirna Knockdownmentioning

confidence: 99%

The Regulatory Role of GBF1 on Osteoclast Activation Through EIF2a Mediated ER Stress and Novel Marker FAM129A Induction

Wen

Zhou

et al. 2021

Front. Cell Dev. Biol.

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“…However, studies with greater sample sizes are needed to confirm this finding. In a recent study [ 42 ], researchers inhibited the secretion of MMP9, thus suppressing bone resorption by targeting ATP5B, providing new insight into protecting bones in rheumatoid arthritis (RA). Since osteoclastogenesis is one of the features of TGCT, targeting MMP9 might be a potential therapy.…”

Section: Discussionmentioning

confidence: 99%

Identification of potential diagnostic biomarkers for tenosynovial giant cell tumour by integrating microarray and single-cell RNA sequencing data

Chen,

Zheng,

Zeng

et al. 2023

J Orthop Surg Res

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Purpose Tenosynovial giant cell tumour (TGCT) is a benign hyperplastic and inflammatory disease of the joint synovium or tendon sheaths, which may be misdiagnosed due to its atypical symptoms and imaging features. We aimed to identify biomarkers with high sensitivity and specificity to aid in diagnosing TGCT. Methods Two scRNA-seq datasets (GSE210750 and GSE152805) and two microarray datasets (GSE3698 and GSE175626) were downloaded from the Gene Expression Omnibus (GEO) database. By integrating the scRNA-seq datasets, we discovered that the osteoclasts are abundant in TGCT in contrast to the control. The single-sample gene set enrichment analysis (ssGSEA) further validated this discovery. Differentially expressed genes (DEGs) of the GSE3698 dataset were screened and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were conducted. Osteoclast-specific up-regulated genes (OCSURGs) were identified by intersecting the osteoclast marker genes in the scRNA-seq and the up-regulated DEGs in the microarray and by the least absolute shrinkage and selection operator (LASSO) regression algorithm. The expression levels of OCSURGs were validated by an external dataset GSE175626. Then, single gene GSEA, protein–protein interaction (PPI) network, and gene-drug network of OCSURGs were performed. Result 22 seurat clusters were acquired and annotated into 10 cell types based on the scRNA-seq data. TGCT had a larger population of osteoclasts compared to the control. A total of 159 osteoclast marker genes and 104 DEGs (including 61 up-regulated genes and 43 down-regulated genes) were screened from the scRNA-seq analysis and the microarray analysis. Three OCSURGs (MMP9, SPP1, and TYROBP) were finally identified. The AUC of the ROC curve in the training and testing datasets suggested a favourable diagnostic capability. The PPI network results illustrated the protein–protein interaction of each OCSURG. Drugs that potentially target the OCSURGs were predicted by the DGIdb database. Conclusion MMP9, SPP1, and TYROBP were identified as osteoclast-specific up-regulated genes of the tenosynovial giant cell tumour via bioinformatic analysis, which had a reasonable diagnostic efficiency and served as potential drug targets.

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“…Except for growth factors and cytokines, genetic tools like short hairpin RNAs (shRNAs) and small interfering RNAs (siRNAs) hold promise for controlling osteoclast-mediated bone resorption. For instance, shRNA targeting Ac45, ATP5B, IGSF23, and Sema3A effectively reduced the number of osteoclasts and bone resorption in infected periapical tissues, arthritis mice, and osteoporotic rats, respectively [ [99] , [100] , [101] , [102] ] ( Table 3 ). These factors demonstrate effectiveness against specific signaling pathways and have relatively minor side effects, and therefore have more potential to be adopted in future clinical trials.…”

Section: Engineering Approaches To Manipulate Osteoclast Behaviormentioning

confidence: 99%

Engineering approaches to manipulate osteoclast behavior for bone regeneration

Cheng,

Tian,

Yang

et al. 2024

Materials Today Bio

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Targeted inhibition of ATP5B gene prevents bone erosion in collagen-induced arthritis by inhibiting osteoclastogenesis

Cited by 12 publications

References 33 publications

The Regulatory Role of GBF1 on Osteoclast Activation Through EIF2a Mediated ER Stress and Novel Marker FAM129A Induction

The Regulatory Role of GBF1 on Osteoclast Activation Through EIF2a Mediated ER Stress and Novel Marker FAM129A Induction

Identification of potential diagnostic biomarkers for tenosynovial giant cell tumour by integrating microarray and single-cell RNA sequencing data

Engineering approaches to manipulate osteoclast behavior for bone regeneration

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