Tension Force‐Induced ATP Promotes Osteogenesis Through P2X7 Receptor in Osteoblasts

Abstract

Orthodontic tooth movement induces alveolar bone resorption and formation by mechanical stimuli. Force exerted on the traction side promotes bone formation. Adenosine triphosphate (ATP) is one of the key mediators that respond to bone cells by mechanical stimuli. However, the effect of tension force (TF)-induced ATP on osteogenesis is inadequately understood. Accordingly, we investigated the effect of TF on ATP production and osteogenesis in MC3T3-E1 cells. Cells were incubated in the presence or absence of P2X7 receptor antagonist A438079, and then stimulated with or without cyclic TF (6% or 18%) for a maximum of 24 h using Flexercell Strain Unit 3000. TF significantly increased extracellular ATP release compared to control. Six percent TF had maximum effect on ATP release compared to 18% TF and control. Six percent TF induced the expression of Runx2 and Osterix. Six percent TF also increased the expression of extracellular matrix proteins (ECMPs), ALP activity, and the calcium content in ECM. A438079 blocked the stimulatory effect of 6% TF on the expression of Runx2, Osterix and ECMPs, ALP activity, and calcium content in ECM. This study indicated that TF-induced extracellular ATP is released in osteoblasts, suggesting that TF-induced ATP promotes osteogenesis by autocrine action through P2X7 receptor in osteoblasts. J. Cell. Biochem. 116: 12–21, 2015. © 2014 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals, Inc.

Low‐intensity pulsed ultrasound‐induced ATP increases bone formation via the P2X7 receptor in osteoblast‐like MC3T3‐E1 cells

“…ALPase hydrolyzes ester bonds in organic phosphate compounds under alkaline conditions and plays an important role in bone calcification [34]. Previous our study showed that a one of the mechanical stimuli tension force affects ALPase activity in mineralization of osteoblasts [35]. In this study, we observed that LIPUS enhanced ECM protein expression and increased phosphate concentration and calcium content in the ECM and that A438079 blocked these LIPUS effects.…”

Influence of the three‐dimensional culture of human bone marrow mesenchymal stromal cells within a macroporous polysaccharides scaffold on Pannexin 1 and Pannexin 3

“…Both are activated by ATP, which is involved in osteogenic differentiation, and promote mineralization. Indeed, the activation of P2X7, via ATP or by an agonist, has been shown to induce ALP and cbfa1/runx2 expression by HBMSCs (Kariya et al, ). Moreover, adenine nucleotides have been shown to stimulate bone formation by increasing the expression of osteoblast‐related genes, such as Cbfa1/Runx2 (Ciciarello et al, ).…”

In vitro loading models for tendon mechanobiology

“…The most popular commercially available units are Flexcell International Cooperation (Burlington, NC). Flexcell provides uniform radial and circumferential strain on cells cultured on flexible membranes . Although the loading of this platform might not fully represent the physiological situation, various studies were conducted based on this platform to investigate tendon cell behavior under 2D biaxial loading (Table S2).…”

“…Flexcell provides uniform radial and circumferential strain on cells cultured on flexible membranes. 63 Although the loading of this platform might not fully represent the physiological situation, various studies were conducted based on this platform to investigate tendon cell behavior under 2D biaxial loading (Table S2). Loading regimes used in these studies are within the range of 2-12% tension and 0.25-2 Hz.…”