The role of Rho GTPases’ substrates Rac and Cdc42 in osteoclastogenesis and relevant natural medicinal products study

Liu, Yuan; Dou, Yu-sheng; Yan, Liang; Yang, Xiaobin; He, Baorong; Kong, Lingbo; Smith, Wanli W.

doi:10.1042/bsr20200407

Cited by 6 publications

(9 citation statements)

References 78 publications

(88 reference statements)

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“…(2) CDC42 regulates the differentiation of the osteoclasts and osteoblasts, further maintain the function of bone modeling and remodeling. Thus, the downregulation of CDC42 might be correlated with the initiation of the AS 30‐33 …”

Section: Discussionmentioning

confidence: 99%

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PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis

Zhang¹,

Du²,

Mou³

et al. 2022

Clinical Laboratory Analysis

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Objective Cell division cycle 42 (CDC42) regulates the polarization of M2 macrophage and maintains the T cell homeostasis, to participate in multiple autoimmune diseases, while its clinical involvement in ankylosing spondylitis (AS) remains unclear. Hence, the current study aimed to investigate the correlation of CDC42 with clinical characteristics and treatment outcome in AS patients receiving tumor necrosis factor (TNF) inhibitor therapy. Methods Peripheral blood mononuclear cell (PBMC) CDC42 expression was detected at baseline, week (W) 4, W8, and W12 after TNF inhibitor treatment in 91 AS patients and in 50 HCs after enrollment. Furthermore, serum TNF‐α, interferon‐γ (IFN‐γ), interleukin‐10 (IL‐10), and interleukin‐17A (IL‐17A) from AS patients were detected at baseline. Results Blood CDC42 was lower in AS patients compared with HCs (p < 0.001). Additionally, blood CDC42 was negatively linked with CRP (r = −0.349, p = 0.001), BASDAI score (r = −0.243, p = 0.020), and ASDASCRP score (r = −0.238, p = 0.023) in AS patients; however, blood CDC42 was not correlated with other clinical characteristics. Besides, CDC42 was negatively correlated with TNF‐α (r = −0.237, p = 0.024) and IL‐17A (r = −0.339, p = 0.001) but not with IFN‐γ (p = 0.083) or IL‐10 (p = 0.280). Moreover, blood CDC42 was elevated after TNF inhibitor treatment (p < 0.001). Meanwhile, blood CDC42 was not varied at baseline and W4 between response patients and non‐response patients, while it was higher at W8 (p = 0.019) and W12 (p = 0.002) in response patients than in non‐response patients after treatment. Conclusion Blood CDC42 deficiency links with elevated pro‐inflammatory cytokines, disease activity and unsatisfying response to TNF inhibitor in AS patients.

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Section: Discussionmentioning

confidence: 99%

“…Thus, the downregulation of CDC42 might be correlated with the initiation of the AS. 30 , 31 , 32 , 33 …”

Section: Discussionmentioning

confidence: 99%

PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis

Zhang¹,

Du²,

Mou³

et al. 2022

Clinical Laboratory Analysis

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“…Rac1 regulates cytoskeleton recombination, actin polymerization, and leading-edge extension by promoting actin assembly (17), which is necessary for the formation of lamellar lipid membranes and membrane folding (13). Without Rac1 and Rac2, the ability of osteoclasts to form actin cytoskeleton is insufficient (18).…”

Section: Rac1 Regulates Cell Adhesion Morphology and Movementmentioning

confidence: 99%

Rac1, A Potential Target for Tumor Therapy

et al. 2021

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RAS-related C3 botulinum toxin substrate 1 (Rac.1) is one of the important members of Rho GTPases. It is well known that Rac1 is a cytoskeleton regulation protein that regulates cell adhesion, morphology, and movement. Rac1 is highly expressed in different types of tumors, which is related to poor prognosis. Studies have shown that Rac1 not only participates in the tumor cell cycle, apoptosis, proliferation, invasion, migration and angiogenesis, but also participates in the regulation of tumor stem cell, thus promoting the occurrence of tumors. Rac1 also plays a key role in anti-tumor therapy and participates in immune escape mediated by the tumor microenvironment. In addition, the good prospects of Rac1 inhibitors in cancer prevention and treatment are exciting. Therefore, Rac1 is considered as a potential target for the prevention and treatment of cancer. The necessity and importance of Rac1 are obvious, but it still needs further study.

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“…Cell division cycle 42 (CDC42), a member of the Rho GTPase family regulates cytoskeletal reorganization in various ways [32]. Although CDC42SE2 could not be validated in the current study, a previous study confirmed the importance of CDC42 in bone metabolism and bone deterioration [33,34]. In addition, CDC42 is closely correlated with immunity and inflammation [35].…”

Section: Proteasome Associated With Ho In Asmentioning

confidence: 63%

Low expression of TCP1 (T-Complex 1) and PSMC1 (Proteasome 26S subunit, ATPase 1) in heterotopic ossification during ankylosing spondylitis

et al. 2021

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Heterotopic ossification (HO) is frequently seen in patients with spinal injuries. Therefore, this study aimed to characterize the association of HO with ankylosing spondylitis (AS) through gene expression profiling. The human transcriptomic datasets (GSE73754 and GSE94683) were obtained from the Gene Expression Omnibus database for analysis. Overlapping differentially expressed genes (DEGs) were identified between AS and HO disease states. Subsequently, weighted gene co-expression network analysis (WGCNA) was performed for constructing and identifying hub genes for each condition. Finally, a consensus of the overlapping DEGs and the hub genes in AS and HO was taken for determining the key genes involved in AS-induced HO. Quantitative realtime polymerase chain reaction and western blotting were used to detect the mRNA and protein expression levels in mesenchymal stem cells of AS patients and controls. Additionally, immunohistochemistry was performed on interspinous ligament samples for experimental validation of genes. DEG analysis identified 355 overlapping genes between HO and AS. WGCNA indicated that the salmon module of the 22 modules constructed, was most significantly correlated with ASinduced HO. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the salmon module indicated the presence of genes enriched in proteasome regulatory particle and proteasome pathways. mRNA expression analysis identified TCP1 and PSMC1 as the key genes in AS-induced HO. Further validation of these genes could help elucidate their role in the complex association of AS and HO.

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The role of Rho GTPases’ substrates Rac and Cdc42 in osteoclastogenesis and relevant natural medicinal products study

Cited by 6 publications

References 78 publications

PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis

PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis

Rac1, A Potential Target for Tumor Therapy

Low expression of TCP1 (T-Complex 1) and PSMC1 (Proteasome 26S subunit, ATPase 1) in heterotopic ossification during ankylosing spondylitis

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