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Biological Compatibility Profile on Biomaterials for Bone Regeneration
Published on: November 16, 2018
Differential effects of TGF-beta isoforms on murine fetal dural cells and calvarial osteoblasts
David S Cabiling1, Elizabeth Kim, David Yan
1Philadelphia, Pa. From the Department of Surgery and Division of Plastic Surgery, The Children's Hospital of Philadelphia.
Background:
Proteins within the transforming growth factor (TGF)-beta family play a central role in both normal and pathologic calvarial morphogenesis. Previous work has suggested differential functions of the TGF-beta isoforms in these processes. Little is known, however, about effects of TGF-betas on the underlying dura. Furthermore, studies on the effects of TGF-beta isoforms on osteoblasts have been conflicting. The purpose of this study was to determine the effect of TGF-beta isoforms, specifically TGF-beta1 and TGF-beta3, on fetal calvarial osteoblast and dural cell differentiation, proliferation, and apoptosis.
Methods:
Primary cultures of fetal calvarial osteoblasts and dural cells were established from embryonic day-18 CD-1 mice. Cells were treated for 48 hours with TGF-beta1 or TGF-beta3. Northern blot analysis, cell counts, and apoptosis assays were performed.
Results:
In dural cells, TGF-beta1 stimulated the expression of early osteodifferentiation genes and resulted in a slight decrease in cell number and no effect on apoptosis. Similar results were observed in osteoblasts. TGF-beta3 had little or no effect on the genes studied in both cell types but resulted in increased apoptosis and concomitant decreases in cell number in both cell types.
Conclusions:
This study demonstrates that dural cells respond to TGF-beta and that this response is isoform-specific. TGF-beta1 stimulates osteodifferentiation of previously uncommitted cells in the dura. It also stimulates early events in bone matrix deposition and has little effect on late markers of bone differentiation in osteoblasts and dural cells. Both isoforms result in decreases in cell number. TGF-beta3 results in greater decreases in cell number and isoform-specific stimulation of apoptosis in both dural cells and calvarial osteoblasts.
Insights
Transforming growth factor-beta1 (TGF-beta1) promotes osteodifferentiation in dura and osteoblast cells. TGF-beta3, however, increases apoptosis and reduces cell numbers in both cell types, indicating isoform-specific effects.
Area of Science:
- Cell biology
- Developmental biology
- Biochemistry
Background:
- Transforming growth factor-beta (TGF-beta) family proteins are crucial for calvarial bone development.
- Differential roles of TGF-beta isoforms in morphogenesis are suggested, but their effects on dura and osteoblasts are unclear.
- Conflicting findings exist regarding TGF-beta isoform effects on osteoblasts.
Purpose of the Study:
- To investigate the effects of TGF-beta1 and TGF-beta3 on fetal calvarial osteoblast and dural cell differentiation, proliferation, and apoptosis.
Main Methods:
- Primary cultures of mouse fetal calvarial osteoblasts and dural cells were established.
- Cells were treated with TGF-beta1 or TGF-beta3 for 48 hours.
- Analysis included Northern blots, cell counts, and apoptosis assays.
Main Results:
- TGF-beta1 stimulated osteodifferentiation gene expression in dural cells and had similar effects on osteoblasts, with minor impacts on cell number and apoptosis.
- TGF-beta3 showed minimal effects on differentiation genes but increased apoptosis and decreased cell number in both cell types.
Conclusions:
- Dural cells exhibit an isoform-specific response to TGF-beta.
- TGF-beta1 promotes osteodifferentiation in the dura and early bone matrix deposition.
- TGF-beta3 induces apoptosis and reduces cell proliferation in both dural cells and osteoblasts.
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