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Published on: December 10, 2010
Protamine stimulates bone sialoprotein gene expression.
Liming Zhou1, Hiroyoshi Matsumura, Masaru Mezawa
1Department of Periodontology, Nihon University School of Dentistry at Matsudo, Chiba, 271-8587, Japan.
Gene
|December 26, 2012
Summary
Protamine, a sperm protein, stimulates bone sialoprotein (BSP) gene transcription in osteoblasts. It targets specific DNA elements (CRE, FRE, HOX) and involves key transcription factors for bone metabolism regulation.
Area of Science:
- Molecular Biology
- Biochemistry
- Bone Biology
Background:
- Protamine is an arginine-rich nuclear protein crucial for sperm DNA stabilization.
- Protamine exhibits diverse biological activities, including roles in bone metabolism.
- Bone sialoprotein (BSP) is vital for bone mineralization, expressed by osteoblasts.
Purpose of the Study:
- To investigate the effect of protamine on bone sialoprotein (BSP) gene expression.
- To elucidate the molecular mechanisms underlying protamine-induced BSP transcription in osteoblasts.
Main Methods:
- Osteoblast-like cells (ROS 17/2.8) and rat bone marrow stromal cells were used.
- BSP mRNA levels and luciferase reporter gene activity were measured following protamine treatment.
- Inhibition studies using kinase inhibitors and transcription factor-specific antibodies were performed.
- Gel shift assays were conducted to assess protein-DNA interactions.
Main Results:
- Protamine significantly increased BSP mRNA levels and luciferase activity in reporter constructs.
- Protamine's effects were mediated through cAMP response element (CRE), fibroblast growth factor 2 response element (FRE), and homeodomain protein-binding site (HOX) in the BSP promoter.
- Protamine enhanced the binding of nuclear proteins, including CREB, c-Fos, c-Jun, JunD, Fra2, Dlx5, Msx2, Runx2, and Smad1, to these regulatory sites.
Conclusions:
- Protamine induces BSP transcription by directly targeting CRE, FRE, and HOX elements in the rat BSP gene promoter.
- Specific transcription factors (phospho-CREB, c-Fos, c-Jun, JunD, Fra2, Dlx5, Msx2, Runx2, Smad1) are critical regulators of protamine's action on BSP gene expression.
