High-magnitude mechanical strain inhibits the differentiation of bone-forming rat calvarial progenitor cells

Fushiki, Rena; Mayahara, Kotoe; Ogawa, Motoyuki; Takahashi, Yasuyo; Kobayashi, Yôko; Tsurumachi, Niina; Tamura, Takahiko

doi:10.3109/03008207.2015.1040878

Cited by 13 publications

(19 citation statements)

References 30 publications

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“…(18% elongations at 6 cycles/min) significantly inhibited bone nodule formation and reduced BMP-2, Runx2, and muscle segment homeobox 2 (Msx2) expression in rat calvarial cells (5). These findings suggest that optimal force enhances, while excessive force inhibits, bone formation.…”

Section: Effect Of Mechanical Strain-induced Pge 2 Production On Bonementioning

confidence: 79%

“…The procedures used for osteogenic cell isolation and culture were previously described by Fushiki et al (5) and Bellows et al (11).…”

Section: Rat Calvarial Cell Culture Proceduresmentioning

confidence: 99%

“…Calvarial cells were exposed to mechanical strain with or without 10 -6 M NS-398 (Merck KGaA, Darmstadt, Germany), a selective inhibitor of COX-2, as described by Fushiki et al (5). Control cells (Control) and control cells supplemented with NS-398 (Control+NS) were loaded with 0% elongation and cultured on plates of the same type.…”

Section: Mechanical Strain Loadingmentioning

confidence: 99%

“…At 18 days after TF loading, bone nodule area was assayed using the von Kossa technique as previously described (5). The area of von Kossa-stained bone nodules in each well was measured with ImageJ software (ver.…”

Section: Measurement Of Bone Nodule Areamentioning

confidence: 99%

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Effect of mechanical strain-induced PGE<sub>2</sub> production on bone nodule formation by rat calvarial progenitor cells

et al. 2019

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High-magnitude mechanical strain inhibits bone nodule formation by reducing expression of bone morphogenetic protein-2 (BMP-2), Runt-related transcription factor 2 (Runx2), and muscle segment homeobox 2 (Msx2). Mechanical strain also induces production of proinflammatory factor prostaglandin E 2 (PGE 2) by osteoblasts. We measured the effect of mechanical strain-induced PGE 2 production on bone nodule formation and expression levels of bone formation-related factors. Osteoblast-like cells isolated from fetal rat calvariae were loaded with 18% cyclic tension force (TF) for 48 h in the presence or absence of NS-398, a selective inhibitor of cyclooxygenase-2. To investigate the effect of TF-induced PGE 2 on bone formation, bone nodule area on day 21 was measured by von Kossa staining. BMP-2, Runx2, and Msx2 expression levels were examined at 1 day after TF loading. Bone nodule formation was significantly inhibited by TF but was restored to control level by PGE 2 inhibition. Furthermore, TF loadinginduced reductions in expressions of these factors were restored to control level by PGE 2 suppression. These results indicate that PGE 2 production induced by high-magnitude mechanical strain inhibits bone nodule formation by reducing expression levels of bone formation-related factors.

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Section: Effect Of Mechanical Strain-induced Pge 2 Production On Bonementioning

confidence: 79%

“…The procedures used for osteogenic cell isolation and culture were previously described by Fushiki et al (5) and Bellows et al (11).…”

Section: Rat Calvarial Cell Culture Proceduresmentioning

confidence: 99%

Section: Mechanical Strain Loadingmentioning

confidence: 99%

Section: Measurement Of Bone Nodule Areamentioning

confidence: 99%

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Effect of mechanical strain-induced PGE<sub>2</sub> production on bone nodule formation by rat calvarial progenitor cells

et al. 2019

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“…1,2 Numerous studies have shown that mechanical stimulation increases bone formation in modelling the skeleton, whereas reduced mechanical loading, as observed in patients subjected to prolonged immobilization or bed rest and in astronauts in a microgravity environment, results in reduced bone mass. [3][4][5][6] Impaired osteoblast proliferation is believed to play an important role in microgravity-induced bone loss. 7,8 The mechanisms by which microgravity exerts these detrimental effects on osteoblast proliferation remain unclear and merit further research.…”

Section: Introductionmentioning

confidence: 99%

miR‐181c‐5p mediates simulated microgravity‐induced impaired osteoblast proliferation by promoting cell cycle arrested in the G₂ phase

Sun

Liu

Wang

et al. 2019

J Cellular Molecular Medi

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Impaired osteoblast proliferation plays fundamental roles in microgravity‐induced bone loss, and cell cycle imbalance may result in abnormal osteoblast proliferation. However, whether microgravity exerts an influence on the cell cycle in osteoblasts or what mechanisms may underlie such an effect remains to be fully elucidated. Herein, we confirmed that simulated microgravity inhibits osteoblast proliferation. Then, we investigated the effect of mechanical unloading on the osteoblast cell cycle and found that simulated microgravity arrested the osteoblast cell cycle in the G 2 phase. In addition, our data showed that cell cycle arrest in osteoblasts from simulated microgravity was mainly because of decreased cyclin B1 expression. Furthermore, miR‐181c‐5p directly inhibited cyclin B1 protein translation by binding to a target site in the 3′UTR. Lastly, we demonstrated that inhibition of miR‐181c‐5p partially counteracted cell cycle arrest and decreased the osteoblast proliferation induced by simulated microgravity. In conclusion, our study demonstrates that simulated microgravity inhibits cell proliferation and induces cell cycle arrest in the G 2 phase in primary mouse osteoblasts partially through the miR‐181c‐5p/cyclin B1 pathway. This work may provide a novel mechanism of microgravity‐induced detrimental effects on osteoblasts and offer a new avenue to further investigate bone loss induced by mechanical unloading.

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Simulated microgravity reduces intracellular‐free calcium concentration by inhibiting calcium channels in primary mouse osteoblasts

Sun

Liu

Zhou

et al. 2018

J of Cellular Biochemistry

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Calcium homeostasis in osteoblasts plays fundamental roles in the physiology and pathology of bone tissue. Various types of mechanical stimuli promote osteogenesis and increase bone formation elicit increases in intracellular-free calcium concentration in osteoblasts. However, whether microgravity, a condition of mechanical unloading, exerts an influence on intracellular-free calcium concentration in osteoblasts or what mechanisms may underlie such an effect are unclear. Herein, we show that simulated microgravity reduces intracellular-free calcium concentration in primary mouse osteoblasts. In addition, simulated microgravity substantially suppresses the activities of L-type voltage-sensitive calcium channels, which selectively allow calcium to cross the plasma membrane from the extracellular space. Moreover, the functional expression of ryanodine receptors and inositol 1,4,5-trisphosphate receptors, which mediate the release of calcium from intracellular storage, decreased under simulated microgravity conditions. These results suggest that simulated microgravity substantially reduces intracellular-free calcium concentration through inhibition of calcium channels in primary mouse osteoblasts. Our study may provide a novel mechanism for microgravity-induced detrimental effects in osteoblasts, offering a new avenue to further investigate bone loss induced by mechanical unloading.

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High-magnitude mechanical strain inhibits the differentiation of bone-forming rat calvarial progenitor cells

Abstract: The differentiation of bone forming progenitor cells into bone nodule forming cells was inhibited by TF due to the decreased expression of bone formation related factors such as BMP-2, Runx2 and Msx2.

Cited by 13 publications

References 30 publications

Effect of mechanical strain-induced PGE<sub>2</sub> production on bone nodule formation by rat calvarial progenitor cells

Effect of mechanical strain-induced PGE<sub>2</sub> production on bone nodule formation by rat calvarial progenitor cells

miR‐181c‐5p mediates simulated microgravity‐induced impaired osteoblast proliferation by promoting cell cycle arrested in the G₂ phase

Simulated microgravity reduces intracellular‐free calcium concentration by inhibiting calcium channels in primary mouse osteoblasts

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High-magnitude mechanical strain inhibits the differentiation of bone-forming rat calvarial progenitor cells

Abstract: The differentiation of bone forming progenitor cells into bone nodule forming cells was inhibited by TF due to the decreased expression of bone formation related factors such as BMP-2, Runx2 and Msx2.

Cited by 13 publications

References 30 publications

Effect of mechanical strain-induced PGE<sub>2</sub> production on bone nodule formation by rat calvarial progenitor cells

Effect of mechanical strain-induced PGE<sub>2</sub> production on bone nodule formation by rat calvarial progenitor cells

miR‐181c‐5p mediates simulated microgravity‐induced impaired osteoblast proliferation by promoting cell cycle arrested in the G2 phase

Simulated microgravity reduces intracellular‐free calcium concentration by inhibiting calcium channels in primary mouse osteoblasts

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miR‐181c‐5p mediates simulated microgravity‐induced impaired osteoblast proliferation by promoting cell cycle arrested in the G₂ phase