2019
DOI: 10.1002/jbm.a.36597
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Mechanical loading induced osteocyte apoptosis and connexin 43 expression in three‐dimensional cell culture and dental implant model

Abstract: Osteocytes are thought to act as stress sensors, and are known to display a gap junction‐mediated stress‐transfer mechanism. To demonstrate the stress‐related function of osteocytes, cells of an osteocyte‐like cell line derived from murine long bone osteocyte Y4 (MLO‐Y4) were cultivated in a three‐dimensional culture and subjected to cyclic loading from a titanium plate. This application of physiological loading using a titanium plate significantly increased connexin 43 (Cx43) expression, the number of dead an… Show more

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Cited by 18 publications
(14 citation statements)
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“…Optimal mechanical loading induces osteocyte functions and survival. However, excessive force on bone induces osteocyte apoptosis and expression of RANKL in osteocytes, which induces osteoclast formation and bone resorption [89]. It is apparent that osteocyte RANKL expression is induced via local and systemic routes, which in turn also functions locally, affecting nearby cells or systemically in models of systemic inflammatory diseases.…”
Section: Rankl and Opgmentioning
confidence: 99%
“…Optimal mechanical loading induces osteocyte functions and survival. However, excessive force on bone induces osteocyte apoptosis and expression of RANKL in osteocytes, which induces osteoclast formation and bone resorption [89]. It is apparent that osteocyte RANKL expression is induced via local and systemic routes, which in turn also functions locally, affecting nearby cells or systemically in models of systemic inflammatory diseases.…”
Section: Rankl and Opgmentioning
confidence: 99%
“…Osteocytes are good mechanosensors (i.e., they detect changes of mechanical stimuli) in bone tissue which serve to sense and respond to alterations produced when a bone is mechanically loaded. Such alterations may be physical deformation of the bone matrix, fluid flow shear stress generated by variations in canalicular fluid flow and electrical streaming potentials (Bonewald and Mundy, 1990;Mundy, 1993;Manolagas, 2000;Miyauchi et al, 2000;Bonewald and Johnson, 2008;Datta et al, 2008;Parra-Torres et al, 2013;Takemura et al, 2019). Mechanical strain signal is converted into a cellular response (i.e., biochemical signals) with the participation of membrane proteins (such as CD44, connexins, integrins, and ion channels) and downstream mediators of intracellular signaling (such as guanine regulatory proteins, mitogen activated protein kinase, cyclic adenosine monophosphate, inositol triphosphate, and intracellular calcium) (Rawlinson et al, 1996;Burger and Klein-Nulend, 1999;Mikuni-Takagaki, 1999;Miyauchi et al, 2000;Gu et al, 2001;Alford et al, 2003;Kapur et al, 2003;Plotkin et al, 2005;Rubin et al, 2006;Miyauchi et al, 2006).…”
Section: Origin Of Osteocytesmentioning
confidence: 99%
“…Sixty-seven articles were reviewed in full text, of which 32 articles met the inclusion criteria for the current review. After reading these articles, another three articles were found to be eligible for inclusion, resulting in a total number of 35 articles included in this study describing 3D-culture models (Table 1) [15••, 24••, 25••].
Fig. 1Study flow of the selection process of the articles used in this review
…”
Section: Resultsmentioning
confidence: 99%
“…Recently, several materials and techniques have been developed to mimic the environment of osteocytes in vivo in 3D models. One such model comprises MLO-Y4 cells suspended in a gel that is mixed with neutralized collagen solution and Matrigel™ [24••, 49]. To mimic the physiological loading sensed by osteocytes around an implant, a titanium plate embedded in the gel was subjected to cyclic stress for 24 h. In this model, MLO-Y4 cells connected by their processes in the collagen/Matrigel mixture like in the lacuno-canalicular network in vivo display increased Cx43 expression and cell apoptosis after cyclic stress treatment, similar to results observed in a mouse model [24••].…”
Section: Resultsmentioning
confidence: 99%