title: Thermally induced osteocyte damage initiates pro-osteoclastogenic gene expression in vivo.
abstract: Bone is often subject to harsh temperatures during orthopaedic procedures resulting in thermally induced bone damage, which may affect the healing response. Postsurgical healing of bone is essential to the success of surgery, therefore, an understanding of the thermally induced responses of bone cells to clinically relevant temperatures in vivo is required. Osteocytes have been shown to be integrally involved in the bone remodelling cascade, via apoptosis, in micro-damage systems. However, it is unknown whether this relationship is similar following thermal damage. Sprague-Dawley rat tibia were exposed to clinically relevant temperatures (47°C or 60°C) to investigate the role of osteocytes in modulating remodelling related factors. Immunohistochemistry was used to quantify osteocyte thermal damage (activated caspase-3). Thermally induced pro-osteoclastogenic genes (Rankl, Opg and M-csf), in addition to genes known to mediate osteoblast and osteoclast differentiation via prostaglandin production (Cox2), vascularization (Vegf) and inflammatory (Il1a) responses, were investigated using gene expression analysis. The results demonstrate that heat-treatment induced significant bone tissue and cellular damage. Pro-osteoclastogenic genes were upregulated depending on the amount of temperature elevation compared with the control. Taken together, the results of this study demonstrate the in vivo effect of thermally induced osteocyte damage on the gene expression profile.
authors.affiliation: Biomechanics Research Centre (BMEC), Biomedical Engineering, College of Engineering and Informatics, National University of Ireland, Galway, Republic of Ireland.
authors.forename: Eimear B
authors.initials: EB
authors.lastname: Dolan
authors.affiliation: Stryker Instruments, Cork, Republic of Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Tallon
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
authors.forename: Wing-Yee
authors.initials: WY
authors.lastname: Cheung
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Schaffler
authors.affiliation: Department of Orthopaedics, New York University School of Medicine, New York, NY, USA.
authors.forename: Oran D
authors.initials: OD
authors.lastname: Kennedy
authors.affiliation: Biomechanics Research Centre (BMEC), Biomedical Engineering, College of Engineering and Informatics, National University of Ireland, Galway, Republic of Ireland laoise.mcnamara@nuigalway.ie.
authors.forename: Laoise M
authors.initials: LM
authors.lastname: McNamara
mesh_terms: D000818:Animals; D016723:Bone Remodeling; D053148:Caspase 3 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006358:Hot Temperature; D053582:Interleukin-1alpha / Q000096:biosynthesis; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D010011:Osteocytes / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin / Q000096:biosynthesis; D053245:RANK Ligand / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D053582:Interleukin-1alpha; D053244:Osteoprotegerin; D053245:RANK Ligand; C506032:Tnfrsf11b protein, rat; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D016173:Macrophage Colony-Stimulating Factor; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: apoptosis; osteocyte; remodelling; thermal damage