Current Topics in Pharmacological Research on Bone Metabolism : Promyelotic Leukemia Zinc Finger (PLZF) and Tumor Necrosis Factor-α-Stimulated Gene 6 (TSG-6) Identified by Gene Expression Analysis Play Roles in the Pathogenesis of Ossification of the Post
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概要
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To understand the molecular pathogenesis of ossification of the posterior longitudinal ligament of the spine (OPLL), an ectopic bone formation disease, we performed cDNA microarray analysis on cultured ligament cells from OPLL patients to understand the molecular pathogenesis of OPLL. We identified promyelotic leukemia zinc finger (PLZF) as one of up-regulated genes and tumor necrosis factor-α-stimulated gene 6 (TSG-6) as one of down-regulated gene during osteoblastic differentiation. We investigated the roles of PLZF in the regulation of osteoblastic differentiation of human mesenchymal stem cells (hMSCs) and C2C12 cells. siRNA-mediated gene-silencing of PLZF resulted in a reduction of the expression of osteoblast-specific genes such as the alkaline phosphatase, collagen 1A1, Runx2/CBFA1, and osteocalcin genes in the presence of osteogenic differentiation medium (OS) in hMSCs. The overexpression of PLZF induced CBFA1 induction, suggesting that PLZF is an upstream regulator of CBFA1 and thereby participates in promoting the ossification of spinal ligament cells in OPLL patients. Adenoirus-mediated TSG-6 overexpression in hMSCs resulted in suppression of oseoblastic differentiation induced by either BMP-2 or OS. TSG-6 can bind to BMP-2 directly and thereby could inhibit BMP-2 signaling. Taken together, these findings indicate that PLZF and TSG-6 play important roles in early osteoblastic differentiation.
- 2006-03-20
著者
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INOUE Ituro
Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo
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Inoue Ituro
Division Of Genetic Diagnosis Institute Of Medical Science The University Of Tokyo
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Tsukahara So
Division Of Genetic Diagnosis Institute Of Medical Science University Of Tokyo
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Tsukahara So
Division Of Genetic Diagnosis The Institute Of Medical Science The University Of Tokyo
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Ikeda Ryuji
鹿児島大学 医歯学総合研究科薬物動態制御学
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IKEDA Ryuji
Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo
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Ikeda Ryuji
Division Of Genetic Diagnosis The Institute Of Medical Science The University Of Tokyo
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