title: Impact of Gap Junctional Intercellular Communication on MLO-Y4 Sclerostin and Soluble Factor Expression.
abstract: Bone remodeling is a continual process in which old bone is resorbed by osteoclasts and new bone is formed by osteoblasts, providing a mechanism for bones' ability to adapt to changes in its mechanical environment. While the role of osteoblasts and osteoclasts in bone remodeling is well understood, the cellular regulation of bone remodeling is unclear. One theory is that osteocytes, found within bone, play an important role in controlling the bone remodeling response. Osteocytes possess gap junctions, narrow channels that extend between nearby cells and allow communication between cells via the transfer of small molecules and ions. This work investigated the potential role of gap junctional intercellular communication in bone remodeling by exposing osteocyte-like MLO-Y4 cells to mechanical strains and quantifying the expression of soluble factors, including sclerostin, a protein closely associated with bone remodeling. The soluble factors and sclerostin expression were further examined after inhibiting gap junctional intercellular communication to study the impact of the communication. At supraphysiologic strains, the inhibition of gap junctional intercellular communication led to increases in sclerostin expression relative to cells in which communication was present, indicating that the communication may play a significant role in regulating bone remodeling.
authors.affiliation: Department of Biomedical Engineering, The University of Akron, Auburn Science and Engineering Center 275, West Tower, Akron, OH, 44325-0302, USA. sly15@zips.uakron.edu.
authors.forename: S L
authors.initials: SL
authors.lastname: York
authors.affiliation: Department of Cardiovascular Disease, The University of Alabama at Birmingham, McCallum Basic Health Sciences Building 290 A, 1918 University Boulevard, Birmingham, AL, 35294, USA.
authors.forename: P
authors.initials: P
authors.lastname: Sethu
authors.affiliation: Department of Biomedical Engineering, The University of Akron, Auburn Science and Engineering Center 275, West Tower, Akron, OH, 44325-0302, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Saunders
mesh_terms: D028341:Activins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D016723:Bone Remodeling; D002450:Cell Communication / Q000502:physiology*; D002460:Cell Line; D004129:Dimethylpolysiloxanes; D005136:Eye Proteins / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism; D017629:Gap Junctions / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism; D010011:Osteocytes / Q000378:metabolism / Q000502:physiology*; D015843:Serpins / Q000378:metabolism; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D028341:Activins; D048868:Adaptor Proteins, Signal Transducing; D042683:Angiopoietin-1; D004129:Dimethylpolysiloxanes; D005136:Eye Proteins; D037502:Galectin 3; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D014841:von Willebrand Factor; D000099174:Pigment Epithelium-Derived Factor; C467628:Angpt1 protein, mouse; C486030:Sost protein, mouse; C422405:activin A; C013830:baysilon
keywords: Cell–cell communication; In vitro; Mechanotransduction; Osteocyte; Soluble factors