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 and apoptotic cells, and receptor activator of nuclear factor κB ligand expression. Furthermore, the conditioned medium from the loaded osteocytes induced alkaline phosphatase activity in bone marrow cell culture. In addition, we immunohistologically determined whether bone metabolism increased as a result of the occlusal force in the bone surrounding the titanium implants in a rat model. Increased Cx43 expression and apoptotic osteocytes were observed in the loading group as well as a significantly increased number of tartrate‐resistant acid phosphatase‐positive cells. These findings indicate that stress from the implant adversely affected the osteocytes, which may promote osteoclastic and osteoblastic cell formation around the implants. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 815–827, 2019.

Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption

“…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.…”

Destroy to Rebuild: The Connection Between Bone Tissue Remodeling and Matrix Metalloproteinases

“…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).…”

A 3D, Dynamically Loaded Hydrogel Model of the Osteochondral Unit to Study Osteocyte Mechanobiology

“…[27][28][29][30][31][32][33] For example, one study achieved mature osteocyte differentiation in a 3D collagen gel but this culture system lacked mechanical cues. [34] Other studies revealed new effects of direct matrix strains on osteocytes in 3D [27,29,35] such as strain-induced osteocyte regulation of osteoblast bone formation. [27] These prior studies applied matrix strains ranging from 0.4-10%, which exceed physiological levels of strain in bone.…”