Mechanical microenvironments and protein expression associated with formation of different skeletal tissues during bone healing

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• 作者：Gregory J. Miller ; Louis C. Gerstenfeld…
• 关键词：Mechanical environment ; Tissue differentiation ; Pseudarthrosis ; FAK ; RhoA
• 刊名：Biomechanics and Modeling in Mechanobiology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：14
• 期：6
• 页码：1239-1253
• 全文大小：14,603 KB
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• 作者单位：Gregory J. Miller (1)
  Louis C. Gerstenfeld (2)
  Elise F. Morgan (1) (2)
  
  1. Department of Mechanical Engineering, Boston University, Boston, MA, USA
  2. Department of Orthopaedic Surgery, Boston University School of Medicine, Boston, MA, USA
  
• 刊物类别：Engineering
• 刊物主题：Theoretical and Applied Mechanics
  Biomedical Engineering
  Mechanics
  Biophysics and Biomedical Physics
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1617-7940

文摘

Uncovering the mechanisms of the sensitivity of bone healing to mechanical factors is critical for understanding the basic biology and mechanobiology of the skeleton, as well as for enhancing clinical treatment of bone injuries. This study refined an experimental method of measuring the strain microenvironment at the site of a bone injury during bone healing. This method used a rat model in which a well-controlled bending motion was applied to an osteotomy to induce the formation of pseudarthrosis that is composed of a range of skeletal tissues, including woven bone, cartilage, fibrocartilage, fibrous tissue, and clot tissue. The goal of this study was to identify both the features of the strain microenvironment associated with formation of these different tissues and the expression of proteins frequently implicated in sensing and transducing mechanical cues. By pairing the strain measurements with histological analyses that identified the regions in which each tissue type formed, we found that formation of the different tissue types occurs in distinct strain microenvironments and that the type of tissue formed is correlated most strongly to the local magnitudes of extensional and shear strains. Weaker correlations were found for dilatation. Immunohistochemical analyses of focal adhesion kinase and rho family proteins RhoA and CDC42 revealed differences within the cartilaginous tissues in the calluses from the pseudarthrosis model as compared to fracture calluses undergoing normal endochondral bone repair. These findings suggest the involvement of these proteins in the way by which mechanical stimuli modulate the process of cartilage formation during bone healing. Keywords Mechanical environment Tissue differentiation Pseudarthrosis FAK RhoA