The role of nitric oxide in the mechanical repression of RANKL in bone stromal cells

Rahnert, Jill A.; Fan, Xian; Case, Natasha; Murphy, Tamara C.; Grassi, Francesco; Sen, Buer; Rubin, Janet

doi:10.1016/j.bone.2008.03.006

Cited by 33 publications

(23 citation statements)

References 46 publications

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“…Furthermore, in addition to an in vivo experimental system including transgenic mice, many studies have indicated the effect of mechanical stress on the bone's adaptive remodeling behavior in osteocytes (22), osteoblasts (23) and in a co-culture between osteoblasts and osteoclasts (24). Several studies have shown that nitric oxide (NO) acts as a mediator of mechanically induced bone remodeling (10,25,26). However, the direct effect of mechanical stress on the behavior of osteoclasts (27) has only been investigated in a few studies and there is limited information on the effects of the release from mechanical stress, which thus became the focus of the present study.…”

Section: Introductionmentioning

confidence: 99%

Effect of the release from mechanical stress on osteoclastogenesis in RAW264.7 cells

Yoshimura¹

2011

Int J Mol Med

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Abstract. The effects of mechanical stress release on osteoclastogenesis may be as important as those of mechanical stress application. However, the direct effects of mechanical stress on the behavior of osteoclasts has not been thoroughly investigated and there is limited information on the results of the release from mechanical stress. In this study, the effects of mechanical stress application and its release on osteoclast differentiation were examined. The number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts derived from RAW264.7 cells were measured and the expression of osteoclast differentiation genes, which was altered in response to the release from mechanical stress according to the Flexercell tension system was evaluated by real-time PcR. Osteoclast differentiation and fusion were suppressed by mechanical stress application and were rapidly induced after mechanical stress release. The mRNA expression of the osteoclast specific genes, TRAP, matrix metalloproteinase-9 (MMP-9), cathepsin-K (cath-k), calcitonin receptor (cTR), ATPase H + transporting vacuolar proton pump member I (ATP6i), chloride channel-7 (clc7) and dendritic cell-specific transmembrane protein (dc-STAMP) was decreased with mechanical stress application, and increased up to 48 h after the release from it. These alterations in gene mRNA expression were associated with the number of osteoclasts and large osteoclasts. Inducible nitric oxide synthetase (iNOS) mRNA was increased with mechanical stress and decreased after its release. Nitric oxide (NO) production was increased with mechanical stress. Nuclear factor of activated T cells cytoplasmic (NFATc) family mRNAs were not altered with mechanical stress, but were up-regulated up to 48 h after the release from it. These findings indicate that the suppression of osteoclast differentiation and fusion induced by mechanical stress is the result of NO increase via iNOS, and that the promotion of osteoclast differentiation and fusion after the release from mechanical stress is related to the NFATc family genes, whose expression remained constant during mechanical stress but was up-regulated after the release from mechanical stress.

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Section: Introductionmentioning

confidence: 99%

Effect of the release from mechanical stress on osteoclastogenesis in RAW264.7 cells

Yoshimura¹

2011

Int J Mol Med

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“…The direct effect of mechanical stimulation on the behavior of osteoclast-like cells has only been investigated in a few studies [Rubin et al, 1997[Rubin et al, , 1999Kurata et al, 2001;Burger et al, 2003;MacQuarrie et al, 2004;Rahnert et al, 2008;Stadelmann et al, 2008].…”

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confidence: 99%

Effect of Mechanical Stimulation on Osteoblast- and Osteoclast-Like Cells in vitro

Kadow-Romacker

Hoffmann

Duda

et al. 2008

Cells Tissues Organs

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Bone-forming osteoblasts and bone-resorbing osteoclasts play an important role during maintenance, adaptation and healing of bone, and both cell types are influenced by physical activity. The aim of the present study was to investigate the effect of a narrow mechanical stimulation window on osteoblast- and osteoclast-like cells. Primary human cells were cultured on a bone-like structure (dentine) and three-point bending with approximately 1,100 microstrain was applied to the dentine at varying frequencies (0.1 and 0.3 Hz) and duration (1, 3 and 5 min daily over 5 days) resulting in different patterns of mechanical stimulation of osteoblast- and osteoclast-like cells. The longest stimulation (5 min at 0.1 Hz) induced a significant increase in osteoblast alkaline phosphatase activity and a significant decrease in osteoprotegerin (OPG) production, and resulted in a significant increase in the soluble receptor activator of NF-κB ligand (sRANKL)/OPG ratio towards sRANKL in comparison to the unstimulated osteoblast-like cells. All stimulations caused a significant decrease in collagen type 1 synthesis. Stimulation for 1 min at 0.3 Hz decreased the fusion and resorption activity of the osteoclast-like cells. These results demonstrate a direct effect of mechanical stimuli on osteoblast-like cells as well as on osteoclast formation and activity in vitro. The change in the sRANKL/OPG ratio towards the stimulation of osteoclastogenesis stresses the necessity to investigate the effect of the same stimulation parameter on the co-culture of both cell types.

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“…It has been shown to be a mitogen for MSC and, furthermore, the simultaneous treatment of OGP and basic fibroblast growth factor (bFGF) results in a three-fold stimulatory effect as compared to OGP alone on MSC (Guido et al, 2002). It has been well documented that the stimulation of MSC to differentiate into osteoblasts is characterized mainly by increased expression of ALP and BGP (Rahnert et al, 2008). Chen et al have found that OGP promotes osteogenesis and inhibits adipogenesis as evidenced by a decrease in adipocyte numbers and an increase in ALP activity and mineralized nodule numbers.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic actions of the osteogenic growth peptide on bovine marrow mesenchymal stromal cells in culture

Zhu¹,

Guo²,

Yang³

et al. 2008

Vet. Med. - Czech

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S:The osteogenic growth peptide (OGP) regulates the differentiation of marrow mesenchymal stem cells derived from human and rodent cell lines into osteoblasts. Whether OGP directly regulates the bovine marrow mesenchymal stem cells differentiating into osteoblasts remains unknown. In this study, we evaluated the effects of OGP on the growth and differentiation of bovine marrow mesenchymal stem cells in culture. Our results showed that OGP promoted osteogenic differentiation of the bovine stem cells. OGP increased alkaline phosphatase (ALP) activity and mineralized nodule formation, and stimulated osteoblast-specific mRNA expression of Osteocalcin (BGP). On the other hand, OGP dose-dependently stimulated the expression of endothelial nitric oxide synthases. These results show for the first time a direct osteogenic effect of OGP on bovine marrow stromal cells in culture, which could be mediated by induction of endothelial nitric oxide synthases.

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The role of nitric oxide in the mechanical repression of RANKL in bone stromal cells

Cited by 33 publications

References 46 publications

Effect of the release from mechanical stress on osteoclastogenesis in RAW264.7 cells

Effect of the release from mechanical stress on osteoclastogenesis in RAW264.7 cells

Effect of Mechanical Stimulation on Osteoblast- and Osteoclast-Like Cells in vitro

Osteogenic actions of the osteogenic growth peptide on bovine marrow mesenchymal stromal cells in culture

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