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Laser Capture Microdissection of Mouse Embryonic Cartilage and Bone for Gene Expression Analysis
Published on: December 18, 2019
Nuclear factor-E2-related factor-1 mediates ascorbic acid induction of osterix expression via interaction with
Weirong Xing1, Anny Singgih, Anil Kapoor
1Musculoskeletal Disease Center, Jerry L Pettis Memorial Veterans Affairs Medical Center, Loma Linda, CA 92357, USA.
The Journal of Biological Chemistry
|May 19, 2007
Summary
Ascorbic acid (AA) regulates bone formation by increasing osterix expression through Nrf1 activation. This mechanism is crucial for osteoblast differentiation and may offer new therapeutic targets for bone fractures.
Area of Science:
- Molecular Biology
- Bone Biology
- Nutritional Biochemistry
Background:
- Spontaneous fractures are linked to the gulonolactone oxidase gene deletion, impacting ascorbic acid (AA) synthesis.
- Understanding how AA influences osteoblast differentiation is critical for bone health research.
Purpose of the Study:
- To elucidate the molecular mechanisms by which ascorbic acid (AA) regulates osteoblast differentiation.
- To investigate the role of Nrf1 and antioxidant-responsive element (ARE) in AA-mediated osterix expression.
Main Methods:
- Utilized bone marrow stromal (BMS) cells from spontaneous fracture mice.
- Performed gene expression analysis, gel mobility shift assays, chromatin immunoprecipitation, and reporter assays.
- Investigated the effect of AA treatment and Nrf1 knockdown on osterix expression and BMS cell differentiation.
Main Results:
- AA treatment significantly increased osterix expression and Nrf1 nuclear accumulation in BMS cells.
- Nrf1 was confirmed to bind to the antioxidant-responsive element (ARE) in the osterix promoter.
- Nrf1 knockdown blocked AA-induced osterix expression and impaired osteoblast differentiation.
Conclusions:
- Ascorbic acid (AA) modulates osterix expression via a novel mechanism involving Nrf1 nuclear translocation and binding to the ARE.
- This pathway is critical for activating genes essential for osteoblast differentiation and bone formation.
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