Tension force causes cell cycle arrest at G2/M phase in osteocyte-like cell line MLO-Y4
Bone remodelling is the process of bone resorption and formation, necessary to maintain bone structure or for adaptation to new conditions. Mechanical loadings, such as exercise, weight bearing and orthodontic force, play important roles in bone remodelling. During the remodelling process, osteocyte...
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Elsevier
2023-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023004437 |
| _version_ | 1811161815675043840 |
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| author | Natsuo Shimizu Kyoko Fujiwara Kotoe Mayahara Mitsuru Motoyoshi Tomihisa Takahashi |
| author_facet | Natsuo Shimizu Kyoko Fujiwara Kotoe Mayahara Mitsuru Motoyoshi Tomihisa Takahashi |
| author_sort | Natsuo Shimizu |
| collection | DOAJ |
| description | Bone remodelling is the process of bone resorption and formation, necessary to maintain bone structure or for adaptation to new conditions. Mechanical loadings, such as exercise, weight bearing and orthodontic force, play important roles in bone remodelling. During the remodelling process, osteocytes play crucial roles as mechanosensors to regulate osteoblasts and osteoclasts. However, the precise molecular mechanisms by which the mechanical stimuli affect the function of osteocytes remain unclear. In the present study, we analysed viability, cell cycle distribution and gene expression pattern of murine osteocyte-like MLO-Y4 cells exposed to tension force (TF). Cells were subjected to TF with 18% elongation at 6 cycles/min for 24 h using Flexcer Strain Unit (FX-3000). We found that TF stimulation induced cell cycle arrest at G2/M phase but not cell death in MLO-Y4 cells. Differentially expressed genes (DEGs) between TF-stimulated and unstimulated cells were identified by microarray analysis, and a marked increase in glutathione-S-transferase α (GSTA) family gene expression was observed in TF-stimulated cells. Enrichment analysis for the DEGs revealed that Gene Ontology (GO) terms and Kyoto Encyclopedia Genes and Genomes (KEGG) pathways related to the stress response were significantly enriched among the upregulated genes following TF. Consistent with these results, the production of reactive oxygen species (ROS) was elevated in TF-stimulated cells. Activation of the tumour suppressor p53, and upregulation of its downstream target GADD45A, were also observed in the stimulated cells. As GADD45A has been implicated in the promotion of G2/M cell cycle arrest, these observations may suggest that TF stress leads to G2/M arrest at least in part in a p53-dependent manner. |
| first_indexed | 2024-04-10T06:20:15Z |
| format | Article |
| id | doaj.art-1cac30653af146bf8982091dde0d5dda |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-10T06:20:15Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
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| series | Heliyon |
| spelling | doaj.art-1cac30653af146bf8982091dde0d5dda2023-03-02T05:00:36ZengElsevierHeliyon2405-84402023-02-0192e13236Tension force causes cell cycle arrest at G2/M phase in osteocyte-like cell line MLO-Y4Natsuo Shimizu0Kyoko Fujiwara1Kotoe Mayahara2Mitsuru Motoyoshi3Tomihisa Takahashi4Department of Orthodontics, Nihon University School of Dentistry, 1-8-3 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan; Division of Applied Oral Science, Nihon University Graduate School of Dentistry, 1-8-3 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, JapanDepartment of Anatomy, Nihon University School of Dentistry, 1-8-3 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan; Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, 1-8-3 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan; Corresponding author. Department of Anatomy, Nihon University School of Dentistry, 1-8-3 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.Department of Orthodontics, Nihon University School of Dentistry, 1-8-3 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan; Division of Clinical Research, Dental Research Centre, Nihon University School of Dentistry, 1-8-3 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, JapanDepartment of Orthodontics, Nihon University School of Dentistry, 1-8-3 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan; Division of Clinical Research, Dental Research Centre, Nihon University School of Dentistry, 1-8-3 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, JapanDepartment of Anatomy, Nihon University School of Dentistry, 1-8-3 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, Japan; Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, 1-8-3 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8310, JapanBone remodelling is the process of bone resorption and formation, necessary to maintain bone structure or for adaptation to new conditions. Mechanical loadings, such as exercise, weight bearing and orthodontic force, play important roles in bone remodelling. During the remodelling process, osteocytes play crucial roles as mechanosensors to regulate osteoblasts and osteoclasts. However, the precise molecular mechanisms by which the mechanical stimuli affect the function of osteocytes remain unclear. In the present study, we analysed viability, cell cycle distribution and gene expression pattern of murine osteocyte-like MLO-Y4 cells exposed to tension force (TF). Cells were subjected to TF with 18% elongation at 6 cycles/min for 24 h using Flexcer Strain Unit (FX-3000). We found that TF stimulation induced cell cycle arrest at G2/M phase but not cell death in MLO-Y4 cells. Differentially expressed genes (DEGs) between TF-stimulated and unstimulated cells were identified by microarray analysis, and a marked increase in glutathione-S-transferase α (GSTA) family gene expression was observed in TF-stimulated cells. Enrichment analysis for the DEGs revealed that Gene Ontology (GO) terms and Kyoto Encyclopedia Genes and Genomes (KEGG) pathways related to the stress response were significantly enriched among the upregulated genes following TF. Consistent with these results, the production of reactive oxygen species (ROS) was elevated in TF-stimulated cells. Activation of the tumour suppressor p53, and upregulation of its downstream target GADD45A, were also observed in the stimulated cells. As GADD45A has been implicated in the promotion of G2/M cell cycle arrest, these observations may suggest that TF stress leads to G2/M arrest at least in part in a p53-dependent manner.http://www.sciencedirect.com/science/article/pii/S2405844023004437OsteocyteMechanical stressTension forceCell cycle arrestOxidative stress |
| spellingShingle | Natsuo Shimizu Kyoko Fujiwara Kotoe Mayahara Mitsuru Motoyoshi Tomihisa Takahashi Tension force causes cell cycle arrest at G2/M phase in osteocyte-like cell line MLO-Y4 Heliyon Osteocyte Mechanical stress Tension force Cell cycle arrest Oxidative stress |
| title | Tension force causes cell cycle arrest at G2/M phase in osteocyte-like cell line MLO-Y4 |
| title_full | Tension force causes cell cycle arrest at G2/M phase in osteocyte-like cell line MLO-Y4 |
| title_fullStr | Tension force causes cell cycle arrest at G2/M phase in osteocyte-like cell line MLO-Y4 |
| title_full_unstemmed | Tension force causes cell cycle arrest at G2/M phase in osteocyte-like cell line MLO-Y4 |
| title_short | Tension force causes cell cycle arrest at G2/M phase in osteocyte-like cell line MLO-Y4 |
| title_sort | tension force causes cell cycle arrest at g2 m phase in osteocyte like cell line mlo y4 |
| topic | Osteocyte Mechanical stress Tension force Cell cycle arrest Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023004437 |
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