Open Access

Bioinformatics analysis identification of AKT3 and RAC1 as key genes in postmenopausal osteoporosis

  • Authors:
    • Liyong Zhang
    • Xiaoming Li
    • Chunfei Wan
    • Weiwei Da
    • Jun Zhang
    • Lihong Fan
    • Qiang Fu
    • Shunmin Xing
    • Yongxiang Wang
  • View Affiliations

  • Published online on: September 7, 2022     https://doi.org/10.3892/etm.2022.11592
  • Article Number: 656
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Postmenopausal osteoporosis (PMO) is an aging‑associated disease that manifests as degradation of bone tissue microstructure leading to decreased bone mass and increased bone fragility. Differentiation of peripheral blood mononuclear cells into osteoclasts is an important process in the development of PMO and identification of key genes that drive differentiation is essential to reveal the mechanism of PMO. The present study combined bioinformatics analysis of a Gene Expression Omnibus dataset of PMO and drug (bisphosphonate) target prediction using the STITCH database to identify hub genes in patients with PMO. Next, the expression of candidate hub genes was assessed in osteoclasts differentiated from THP‑1 cells and small interfering RNA assays were performed to assess the function of selected hub genes. The present study identified 10 hub genes including WNT1, AKT3, disheveled segment polarity protein 1, cyclin D1, H2B clustered histone 17, JUN, EGFR, RAC1, actinin α1 (ACTN1) and ACTN2. Among these, AKT3 and RAC1 were highly upregulated during osteoclast differentiation, and knockdown of AKT3 and RAC1 using small interfering RNA enhanced the inhibitory effect of bisphosphonates on osteoclast differentiation and apoptosis of monocytes as assessed by tartrate‑resistant acid phosphatase staining and flow cytometry examining Annexin V‑FITC/PI staining, respectively. In conclusion, AKT3 and RAC1 were key for development of PMO and inhibiting AKT3 and RAC1 may improve the therapeutic efficacy of bisphosphonates.
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November-2022
Volume 24 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Zhang L, Li X, Wan C, Da W, Zhang J, Fan L, Fu Q, Xing S and Wang Y: Bioinformatics analysis identification of AKT3 and RAC1 as key genes in postmenopausal osteoporosis. Exp Ther Med 24: 656, 2022
APA
Zhang, L., Li, X., Wan, C., Da, W., Zhang, J., Fan, L. ... Wang, Y. (2022). Bioinformatics analysis identification of AKT3 and RAC1 as key genes in postmenopausal osteoporosis. Experimental and Therapeutic Medicine, 24, 656. https://doi.org/10.3892/etm.2022.11592
MLA
Zhang, L., Li, X., Wan, C., Da, W., Zhang, J., Fan, L., Fu, Q., Xing, S., Wang, Y."Bioinformatics analysis identification of AKT3 and RAC1 as key genes in postmenopausal osteoporosis". Experimental and Therapeutic Medicine 24.5 (2022): 656.
Chicago
Zhang, L., Li, X., Wan, C., Da, W., Zhang, J., Fan, L., Fu, Q., Xing, S., Wang, Y."Bioinformatics analysis identification of AKT3 and RAC1 as key genes in postmenopausal osteoporosis". Experimental and Therapeutic Medicine 24, no. 5 (2022): 656. https://doi.org/10.3892/etm.2022.11592