Effects of mechanical stress on cytokine production in mandible‐derived osteoblasts

Yamamoto, Kenta; Yamamoto, Toshiro; Ichioka, Hiroaki; Akamatsu, Yorihiro; Oseko, Fumishige; Mazda, Osam; Imanishi, Jirô; Kanamura, Narisato; Kita, Masakazu

doi:10.1111/j.1601-0825.2011.01832.x

Cited by 24 publications

(21 citation statements)

References 48 publications

(65 reference statements)

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“…A tensile strain upregulated OPG expression of mouse osteoblastic MC3T3-E1 cells and downregulated RANKL expression. Moreover, hydrostatic pressure changed the ratio of RANKL/OPG in favor of RANKL both at the mRNA and protein levels in a magnitude-and time-dependent manner (13). These studies all demonstrated that mechanical stress suppressed osteoclastogenesis and inhibited bone resorption.…”

Section: Discussionmentioning

confidence: 73%

Osteoclastogenesis accompanying early osteoblastic differentiation of BMSCs promoted by mechanical stretch

et al. 2013

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Abstract. Mechanical stress plays a crucial role in bone formation and absorption. In previous studies, we verified the osteoblastogenesis of bone mesenchymal stem cells (BMSCs) affected by intermittent traction stretch. However, little is known about the osteoclastogenesis process under mechanical stimulation and its underlying association with osteoblastogenesis. In the present study, we investigated the osteoclastogenesis of BMSCs under this special mechanical stress. BMSCs were subjected to 10% elongation for 1-7 days using a Flexcell Strain Unit and then the mRNA levels of osteoclastic genes were examined. The results indicated time-dependent varying of mRNA levels of the receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in BMSCs at different stretching time points. The ratio of RANKL/OPG increased at the early stage of mechanical stimulation (5 days) and decreased to a low level at a later stage (7 days). Findings of this study may help to understand the correlations between osteoblastogenesis and osteoclasteogenesis when mechanical stretch induces the osteoblastic differentiation of BMSCs.

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Section: Discussionmentioning

confidence: 73%

Osteoclastogenesis accompanying early osteoblastic differentiation of BMSCs promoted by mechanical stretch

et al. 2013

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“…These previous results suggest that mandible-derived osteoblasts play an important role in inflammatory cytokine production in response to mechanical stress and mechanical stress may regulate the homeostasis of mandible bone by activating bone remodelling through osteoclastogenesis in vivo [16]. Therefore, occlusal force may be a key regulator of regeneration of periodontal tissue, including the alveolar bone and PDL.…”

Section: Discussionmentioning

confidence: 84%

“…Our group has previously reported that mechanical stress increased the inflammatory cytokines production in a magnitude-and time-dependent manner and changed the ratio of receptor activator of nuclear factor kappa-B Odontology ligand/Osteoprotegerin (RANKL/OPG) in favour of RANKL in mandible-derived osteoblasts [16]. These previous results suggest that mandible-derived osteoblasts play an important role in inflammatory cytokine production in response to mechanical stress and mechanical stress may regulate the homeostasis of mandible bone by activating bone remodelling through osteoclastogenesis in vivo [16].…”

Section: Discussionmentioning

confidence: 99%

“…Isolation of RNA and synthesis of cDNA was performed as previously described [16]. Realtime RT-PCR was performed for analysing the mRNA expression levels of the growth factors.…”

Section: Cell Viability Analysismentioning

confidence: 99%

“…To analyse the role of the MAPK signalling pathway on biomechanical force-induced growth factor expression, hPDL cells were pre-treated with each of the following MAPK inhibitors: ERK1/2 pathway inhibitor, PD98059 (Cayman Chemical, Ann Arbor, MI, USA); p-38 pathway inhibitor, SB202190 (Cayman Chemical, Ann Arbor, MI, USA); and JNK pathway inhibitor, SP600125 (Enzo Life Science, Farmingdale, NY, USA) at a concentration of 10 lM, 1 h prior to the exposure to biomechanical force [16]. Thereafter, biomechanical force was applied and isolation of RNA and synthesis of cDNA was performed for real-time RT-PCR.…”

Section: Inhibition Of Mapksmentioning

confidence: 99%

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Biomechanical force induces the growth factor production in human periodontal ligament-derived cells

Ichioka

Yamamoto

et al. 2015

Odontology

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Although many reports have been published on the functional roles of periodontal ligament (PDL) cells, the mechanisms involved in the maintenance and homeostasis of PDL have not been determined. We investigated the effects of biomechanical force on growth factor production, phosphorylation of MAPKs, and intracellular transduction pathways for growth factor production in human periodontal ligament (hPDL) cells using MAPK inhibitors. hPDL cells were exposed to mechanical force (6 MPa) using a hydrostatic pressure apparatus. The levels of growth factor mRNA and protein were examined by real-time RT-PCR and ELISA. The phosphorylation of MAPKs was measured using BD™ CBA Flex Set. In addition, MAPKs inhibitors were used to identify specific signal transduction pathways. Application of biomechanical force (equivalent to occlusal force) increased the synthesis of VEGF-A, FGF-2, and NGF. The application of biomechanical force increased the expression levels of phosphorylated ERK and p38, but not of JNK. Furthermore, the levels of VEGF-A and NGF expression were suppressed by ERK or p38 inhibitor. The growth factors induced by biomechanical force may play a role in the mechanisms of homeostasis of PDL.

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VNUT/SLC17A9, a vesicular nucleotide transporter, regulates osteoblast differentiation

et al. 2020

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Osteoblasts release adenosine triphosphate (ATP) out of the cell following mechanical stress. Although it is well established that extracellular ATP affects bone metabolism via P2 receptors [such as purinergic receptor P2X7 (P2X7R) and purinergic receptor P2Y2 (P2Y2R)], the mechanism of ATP release from osteoblasts remains unknown. Recently, a vesicular nucleotide transporter [VNUT, solute carrier family 17 member 9 (SLC17A9)] that preserves ATP in vesicles has been identified. The purpose of this study was to elucidate the role of VNUT in osteoblast bone metabolism. mRNA and protein expression of VNUT were confirmed in mouse bone and in osteoblasts by quantitative real‐time PCR (qPCR) and immunohistochemistry. Next, when compressive force was applied to MC3T3‐E1 cells by centrifugation, the expression of Slc17a9 , P2x7r , and P2y2r was increased concomitant with an increase in extracellular ATP levels. Furthermore, compressive force decreased the osteoblast differentiation capacity of MC3T3‐E1 cells. shRNA knockdown of Slc17a9 in MC3T3‐E1 cells reduced levels of extracellular ATP and also led to increased osteoblast differentiation after the application of compressive force as assessed by qPCR analysis of osteoblast markers such as Runx2, Osterix, and alkaline phosphatase (ALP) as well as ALP activity. Consistent with these observations, knockdown of P2x7r or P2y2r by siRNA partially rescued the downregulation of osteoblast differentiation markers, caused by mechanical loading. In conclusion, our results demonstrate that VNUT is expressed in osteoblasts and that VNUT inhibits osteoblast differentiation in response to compressive force by mechanisms related to ATP release and P2X7R and/or P2Y2R activity.

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Effects of mechanical stress on cytokine production in mandible‐derived osteoblasts

Abstract: These results suggest that MDOB play a role in cytokine production in response to mechanical stress and that occlusal force may support the maintenance of mandible bone homeostasis by activating bone remodeling through osteoclastogenesis.

Cited by 24 publications

References 48 publications

Osteoclastogenesis accompanying early osteoblastic differentiation of BMSCs promoted by mechanical stretch

Osteoclastogenesis accompanying early osteoblastic differentiation of BMSCs promoted by mechanical stretch

Biomechanical force induces the growth factor production in human periodontal ligament-derived cells

VNUT/SLC17A9, a vesicular nucleotide transporter, regulates osteoblast differentiation

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