DMP1 and MEPE expression are elevated in osteocytes after mechanical loading in vivo: theoretical role in controlling mineral quality in the perilacunar matrix.
DMP1 and MEPE expression are elevated in osteocytes after mechanical loading in vivo: theoretical role in controlling mineral quality in the perilacunar matrix.
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发表时间：
2007-10
影响因子：
1.9
通讯作者：
Stephen E. Harris;J. Gluhak‐Heinrich;M. Harris;Wuchen Yang;L. F. Bonewald;D. Riha;Peter S.N. Rowe;A. Robling;C. Turner;Junsheng Feng;M. McKee;D. Nicollela
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作者：
Stephen E. Harris;J. Gluhak‐Heinrich;M. Harris;Wuchen Yang;L. F. Bonewald;D. Riha;Peter S.N. Rowe;A. Robling;C. Turner;Junsheng Feng;M. McKee;D. Nicollela
is more complex. We have identified 200 to 500 nucleotide CNS from -20kb of the transcription start site throughout the transcription unit and in the 20kb 3’ flanking region. Therefore, we are building a DMP1 BAC construct that will have all of these CNS and potential enhancer modules of the DMP1 gene driving a GFP reporter. In parallel, we have constructed a database of all transcription factors that bind within the DMP1 CNS and cross-indexed this set of binding sites with osteocyte selective transcription factors, identified in primary mouse osteocytes as well as other classes of transcription factors. We then constructed a small computational model for testing which regions of the DMP1 gene give the gene its osteocyte specificity and what regions are more likely responsible for the mechanical load responses. DMP1 expression, specifically in osteocytes of the mouse ulna, increases 2to 3-fold at 24 hours after a single 2.4N load for 30 seconds at 2 Hz. We constructed a finite element model (FEA) of the mouse ulna and demonstrated a direct statistically significant correlation between DMP1 expression and computed tissue strains. This correlation shows that DMP1 expression in osteocytes is highest in areas of maximal compressive and tensile strains in cortical bone, in both the longitudinal and cross-sectional axes. DMP1 is an early mechanical response gene as its expression is first elevated at 1hour after loading and continues to increase up to 24hours. Using a 3-D model relating the 3-dimensional strain field with DMP1 expression, the gene expression threshold (GEt) for DMP1 is approximately 1500 Istrain, as shown in Figure 1. Using information on the phenotype of the DMP1 knockout mice where DMP1 appears necessary for normal lacunar J Musculoskelet Neuronal Interact 2007; 7(4):313-315
