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Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
Published on: May 4, 2018
Dioxin-sensitive proteins in differentiating osteoblasts: effects on bone formation in vitro
Donatella Carpi1, Merja Korkalainen, Luisa Airoldi
1Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Abstract:
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine-disrupting environmental pollutant which affects bone tissue, although the mechanistic basis of this action is far from clear. We adopted a proteome approach to investigate the disturbance of osteogenesis evoked by TCDD in an in vitro osteoblast differentiation model of rat mesenchymal stem cells. Eighteen individual proteins showed a significant change in abundance as results of ten days of TCDD exposure, at which time mRNA changes in osteoblast differentiation markers were also observed. These proteins were mostly involved in cytoskeleton organization and biogenesis, actin filament-based processes, protein transport, and folding. The alteration in cell architecture and increase in cell adhesion were confirmed by confocal microscopy. The TCDD-induced decrease in the expression of calcium-binding proteins may interfere with osteoblast calcium deposition, which was in fact reduced by TCDD. This is the first report investigating, at the protein expression level, the effect of TCDD during osteoblastic differentiation. Interestingly, MetaCore pathway analysis grouped the majority of these proteins around two principal nodes (c-fos and c-myc) suggesting that they may participate in the transcriptional activation of key pathways in TCDD-driven inhibition of osteoblast differentiation. Our findings provide evidence of new molecular players in the effects of TCDD on bone development.
Insights
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disruptor, alters bone development by affecting osteoblast differentiation. This study identifies key proteins and pathways involved in TCDD
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Bone Biology
Background:
- 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine-disrupting environmental pollutant with known effects on bone tissue.
- The precise molecular mechanisms by which TCDD impacts osteogenesis remain unclear.
Purpose of the Study:
- To investigate the effects of TCDD on osteoblast differentiation using a proteomic approach.
- To identify specific proteins and pathways affected by TCDD during osteogenesis in vitro.
Main Methods:
- Utilized an in vitro osteoblast differentiation model using rat mesenchymal stem cells.
- Employed a proteome approach to analyze protein abundance changes after TCDD exposure.
- Confirmed cellular alterations using confocal microscopy and analyzed pathway involvement with MetaCore.
Main Results:
- Significant changes in the abundance of 18 proteins were observed after 10 days of TCDD exposure.
- Affected proteins were primarily involved in cytoskeleton organization, actin-based processes, and protein transport.
- TCDD exposure led to altered cell architecture, increased cell adhesion, and reduced calcium deposition.
- A decrease in calcium-binding proteins was noted, potentially impacting osteoblast function.
Conclusions:
- This study provides the first proteomic insights into TCDD's effects on osteoblastic differentiation.
- Identified proteins and pathways, particularly those linked to c-fos and c-myc, suggest novel mechanisms for TCDD-induced inhibition of osteogenesis.
- Findings reveal new molecular players contributing to TCDD's impact on bone development.
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