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. 2021 Oct 14:2021:2909454.
doi: 10.1155/2021/2909454. eCollection 2021.

Overexpression of PIK3R1 Promotes Bone Formation by Regulating Osteoblast Differentiation and Osteoclast Formation

Haitao Zhu  1 , Hua Chen  1 , Degang Ding  1 , Shui Wang  1 , Xiaofeng Dai  1 , Yulong Zhu  1
Affiliations

Overexpression of PIK3R1 Promotes Bone Formation by Regulating Osteoblast Differentiation and Osteoclast Formation

Haitao Zhu et al. Comput Math Methods Med. .

Retraction in

Abstract

In an effort to bolster our understanding of regulation of bone formation in the context of osteoporosis, we screened out differentially expressed genes in osteoporosis patients with high and low bone mineral density by bioinformatics analysis. PIK3R1 is increasingly being nominated as a pivotal mediator in the differentiation of osteoblasts and osteoclasts that is closely related to bone formation. However, the specific mechanisms underlying the way that PIK3R1 affects bone metabolism are not fully elucidated. We intended to examine the potential mechanism by which PIK3R1 regulates osteoblast differentiation. Enrichment analysis was therefore carried out for differentially expressed genes. We noted that the estrogen signaling pathway, TNF signaling pathway, and osteoclast differentiation were markedly associated with ossification, and they displayed enrichment in PIK3R1. Based on western blot, qRT-PCR, and differentiation analysis in vitro, we found that upregulation of PIK3R1 enhanced osteoblastic differentiation, as evidenced by increased levels of investigated osteoblast-related genes as well as activities of ALP and ARS, while it notably decreased levels of investigated osteoclast-related genes. On the contrary, downregulation of PIK3R1 decreased levels of osteoblast-related genes and increased levels of osteoclast-related genes. Besides, in vitro experiments revealed that PIK3R1 facilitated proliferation and repressed apoptosis of osteoblasts but had an opposite impact on osteoclasts. In summary, PIK3R1 exhibits an osteoprotective effect via regulating osteoblast differentiation, which can be represented as a promising therapeutic target for osteoporosis.

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Conflict of interest statement

All authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1
Figure 1
Volcano plot of DEGs. Red (logFC > 0 and p < 0.05) indicates upregulated DEGs. Green (logFC < 0 and p < 0.05) indicates downregulated DEGs.
Figure 2
Figure 2
Enrichment analysis on DEGs and selection of target genes: (a) cellular components; (b) biological processes; (c) molecular functions; (d) KEGG pathway analysis; (e) intersection of genes corresponding to enriched pathways (hsa04915: estrogen signaling pathway; hsa04668: TNF signaling pathway; hsa04380: osteoclast differentiation).
Figure 3
Figure 3
The impact of PIK3R1 on osteoblast differentiation: (a, b) the transfection efficacy of sh-PIK3R1 determined by qRT-PCR and western blotting; (c) the impact of PIK3R1 downregulation on osteoblast differentiation assessed by ALP and ARS staining; (d) the mRNA levels of osteoblast-related genes assayed via qRT-PCR; (e) the protein levels of osteoblast-related genes measured by western blotting; (f, g) the impact of PIK3R1 downregulation on osteoblast proliferation tested through CCK-8 and EdU; (h) the impact of PIK3R1 downregulation on osteoblast apoptosis measured by flow cytometry; ∗p < 0.05.
Figure 4
Figure 4
The impact of PIK3R1 on osteoblast differentiation: (a, b) the transfection efficacy of oe-PIK3R1 determined by qRT-PCR and western blotting; (c) the impact of PIK3R1 upregulation on osteoblast differentiation assessed by ALP and ARS staining; (d) the mRNA levels of osteoblast-related genes assayed via qRT-PCR; (e) the protein levels of osteoblast-related genes measured by western blotting; (f, g) the impact of PIK3R1 upregulation on osteoblast proliferation tested through CCK-8 and EdU; (h) the impact of PIK3R1 upregulation on osteoblast apoptosis measured by flow cytometry; ∗p < 0.05.
Figure 5
Figure 5
The impact of PIK3R1 on osteoclast differentiation: (a, b) the transfection efficacy of sh-PIK3R1 determined by qRT-PCR and western blotting; (c) the mRNA levels of osteoclast-related genes assayed via qRT-PCR; (d) the protein levels of osteoclast-related genes measured by western blotting; (e, f) the impact of PIK3R1 downregulation on osteoclast proliferation tested through CCK-8 and EdU; (g) the impact of PIK3R1 downregulation on osteoclast apoptosis measured by flow cytometry; ∗p < 0.05.
Figure 6
Figure 6
The impact of PIK3R1 on osteoclast differentiation: (a, b) the transfection efficacy of sh-PIK3R1 determined by qRT-PCR and western blotting; (c) the mRNA levels of osteoclast-related genes assayed via qRT-PCR; (d) the protein levels of osteoclast-related genes measured by western blotting; (e, f) the impact of PIK3R1 upregulation on osteoclast proliferation tested through CCK-8 and EdU; (g) the impact of PIK3R1 upregulation on osteoclast apoptosis measured by flow cytometry; ∗p < 0.05.
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