株化骨細胞MLO-Y4-A2におけるPTH受容体遺伝子のメカニカルストレスによる発現

概要

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Osteocytes are generally accepted to function as sensors for mechanical stress, which are deeply involved in bone homeostasis. However, the signal transduction mechanism of mechanical stresses in osteocytes is still mostly unclear. Here the effect of fluid shear stress on gene expressions of MLO-Y4-A2 cells, a murine osteocyte-like cell line, was investigated. When shear stress was loaded on the MLO-Y4-A2 cells, PTH receptor mRNA increased to 5 to 8 times over the control level. The PTH receptor protein and CAMP levels were also increased by the shear stress. The increase in the PTH receptor mRNA was not inhibited by U-0126 (ERK kinase inhibitor) or indomethacin (COX-2 inhibitor). Luciferase reporter analysis indicated that the P1 promoter region of the PTH receptor gene includes cis-elements for transcription control by shear stress. These results suggest that in osteocytes the mechanical stress induces PTH receptor increases, which in turn amplify the effect of PTH and/or PTHrP on bone remodeling.
北海道医療大学の論文