Association of Genes Variants in RANKL/RANK/OPG Signaling Pathway with the Development of Osteonecrosis of the Femoral Head in Chinese Population

Song, Yang; Du, Zhenwu; Yang, Qiwei; Ren, Mingchun; Wang, Qingyu; Wang, Ao; Chen, Gaoyang; Zhao, Hongbo; Yu, Tao; Zhang, Guizhen

doi:10.7150/ijms.19124

Cited by 17 publications

(10 citation statements)

References 26 publications

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“…The cause of traumatic ONFH is clear, but that of non-traumatic ONFH is unknown. [1, 2] Main theories include the osteocyte apoptosis theory, abnormal lipid metabolism theory [3], and osteoporosis theory [4–6]. Even immunological factors play a role in ONFH development [7].…”

Section: Introductionmentioning

confidence: 99%

Correlational analysis between neutrophil granulocyte levels and osteonecrosis of the femoral head

Jiang

Liu

Lai

et al. 2019

BMC Musculoskelet Disord

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Background The correlation between peripheral blood neutrophil level and osteonecrosis of the femoral head (ONFH) has not been extensively studied. Thus, we aimed to investigate the correlation between neutrophil level in the peripheral blood (neutrophil granulocyte) and ONFH. Methods A total of 984 cases of ONFH and femoral neck fractures (non-ONFH) diagnosed at the Department of Orthopedics at our institution between January 1, 2011 and December 31, 2016 were retrospectively reviewed. The ONFH and non-ONFH groups comprised 488 and 496 cases, respectively. Basic information and peripheral blood cell levels of the two groups were compared. Results The patients’ mean age was 59.89 ± 17.06 years (range: 38–82 years). There were 457 male and 527 female patients, with a male-to-female ratio of 1:1.15. We found that neutrophil granulocyte levels and percentage of neutrophil granulocytes were significantly different between the ONFH and non-ONFH groups. Multimodal regression analysis showed that the percentage of neutrophil granulocytes was an independent protective factor against ONFH. Conclusions The factors influencing ONFH are neutrophil granulocyte levels and percentage of neutrophil granulocytes. Percentage of neutrophil granulocytes has a significant correlation with aseptic femoral head necrosis, providing a new perspective and direction for further study of femoral head necrosis.

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Section: Introductionmentioning

confidence: 99%

Correlational analysis between neutrophil granulocyte levels and osteonecrosis of the femoral head

Jiang

Liu

Lai

et al. 2019

BMC Musculoskelet Disord

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“…NFH is a destructive bone disease, mainly induced by disruption of the blood supply and the dysfunction of the coagulation and fibrinolysis systems, which lead to the collapse of the femoral head (26,27). Various molecular and genetic studies have investigated the causes of the disease (28,29); however, the exact pathogenic mechanisms remain unclear. A genome-wide approach was employed to investigate differential gene expression in cartilage samples from patients with NFH and healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Identiﬁcation of differentially expressed genes in hip cartilage with femoral head necrosis, based on genome‑wide expression proﬁles

Bai

et al. 2019

Mol Med Report

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Necrosis of the femoral head (NFH), a severe orthopedic disease in adults, involves the collapse of the femoral head. The pathophysiological mechanisms underlying NFH are yet to be fully investigated. The aim of the present study was to identify potentially important genes and signaling pathways involved in NFH and investigate their molecular mechanisms. Gene expression profiles of patients with NFH and healthy controls were compared using the Gene Expression Omnibus (GEO) database repository of the National Center of Biotechnology Information. GSE74089 from the GEO database included 4 patients with NFH and 4 healthy individuals. A total of 1,191 differentially expressed genes (DEGs) were identified between the patients with NFH and controls, including 743 upregulated and 448 downregulated DEGs. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that upregulated DEGs were mainly involved in the phosphoinositide 3-kinase/protein kinase B signaling pathway, focal adhesion and extracellular matrix-receptor interactions. Additionally, protein-protein interaction (PPI) analysis identified the most central DEGs as vascular endothelial growth factor A, Jun proto-oncogene, cyclin D1, fibroblast growth factor 2, HECT domain and ankyrin repeat-containing E3 ubiquitin protein ligase 1, protein kinase Cα, bone morphogenetic protein 2 and prostaglandin-endoperoxide synthase 2. PPI analysis also identified guanine nucleotide-binding protein, γ13 as the most commonly downregulated gene based on different centrality. The results of the present study may provide novel insight into the genes and associated pathways involved in NFH, and aid the identification of novel therapeutic targets and biomarkers in the treatment of NFH.

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“…Conversely, OPG can inhibit the binding of a RANKL to the RANK receptor [ 19 ]. Therefore, RANKL/RANK/OPG pathway has been an important treatment way for PMOP [ 20 , 21 ]. The balance between bone formation and resorption is maintained by regulating the ratio of OPG/RANKL [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Sirt1/Foxo Axis Plays a Crucial Role in the Mechanisms of Therapeutic Effects of Erzhi Pill in Ovariectomized Rats

Liang

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Background. Erzhi pill (EZP), a traditional Chinese herbal formula, has been widely used to treat postmenopausal osteoporosis (PMOP) in China. However, its molecular mechanisms remain unclear. The aim of the present study is to investigate the antiosteoporotic effect of EZP on an ovariectomized rat model of PMOP. We performed the biomarkers of bone metabolism disorder, bone morphology, bone mineral density (BMD), and bone biomechanics to confirm the successful establishment of the PMOP model. We then investigated the expression of biomarkers related to the Sirt1/Foxo axis. We also examined microRNA-132 (miR-132), a regulator in the Sirtuin1 (Sirt1) expression. The bone metabolism disorder, bone morphology, BMD, and bone biomechanics in ovariectomized rats were improved by EZP administration. The antiosteoporotic effect of EZP was confirmed. We also found that the expressions of Sirt1, Runx2, Foxo1, and Foxo3a were downregulated in ovariectomized rats, while being then upregulated by EZP administration. And the expression of PPAR-γ and miR-132 was upregulated in ovariectomized rats and then downregulated by EZP administration. These results provided evidence that Sirt1/Foxo axis related mechanism may play a crucial role in the therapeutic effects of EZP, indicating that Sirt1/Foxo axis can be considered as a potential therapeutic target for PMOP in the future.

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Association of Genes Variants in RANKL/RANK/OPG Signaling Pathway with the Development of Osteonecrosis of the Femoral Head in Chinese Population

Cited by 17 publications

References 26 publications

Correlational analysis between neutrophil granulocyte levels and osteonecrosis of the femoral head

Correlational analysis between neutrophil granulocyte levels and osteonecrosis of the femoral head

Identiﬁcation of differentially expressed genes in hip cartilage with femoral head necrosis, based on genome‑wide expression proﬁles

Sirt1/Foxo Axis Plays a Crucial Role in the Mechanisms of Therapeutic Effects of Erzhi Pill in Ovariectomized Rats

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