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Skeletal trauma generates systemic BMP2 activation that is temporally related to the mobilization of CD73+ cells.

Marsell R, Steen B, Bais MV, Mortlock DP, Einhorn TA, Gerstenfeld LC - J. Orthop. Res. (2013)

Bottom Line: Stem cell mobilization was analyzed by FACS analysis using CD73, a marker associated with bone marrow stromal stem cells.A ∼20% increase of CD73 positive cells was seen in the peripheral blood 2 days after reaming.These data showed that traumatic bone injury caused a systemic induction of BMP2 expression and that this increase is correlated with the mobilization of CD73 positive cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, Boston University Medical Center, 715 Albany Street, R-205, Boston, 02118, Massachusetts.

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Steady state mRNA expression of morphogens and markers associated with stem cell mobilization whole bone segments from the regions that had been reamed or comparable regions from contralateral and control bones as described in Materials and Methods Section, were used for these studies. qRT-PCR analysis was made for RNAs from (Reamed) bones compared to the (Contralateral) of the traumatized mice and from uninjured mice (Naïve Control) tibia. Data are displayed as fold change versus Naïve Control set as base line (=1). Time after surgery and the nature of each mRNA that was examined is denoted in the figure.
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fig02: Steady state mRNA expression of morphogens and markers associated with stem cell mobilization whole bone segments from the regions that had been reamed or comparable regions from contralateral and control bones as described in Materials and Methods Section, were used for these studies. qRT-PCR analysis was made for RNAs from (Reamed) bones compared to the (Contralateral) of the traumatized mice and from uninjured mice (Naïve Control) tibia. Data are displayed as fold change versus Naïve Control set as base line (=1). Time after surgery and the nature of each mRNA that was examined is denoted in the figure.

Mentions: The systemic nature of BMP2 expression after trauma led us to hypothesize that there would be increased hematopoietic and/or mesenchymal stem cell mobilization throughout the skeleton. In order to test this hypothesis, we chose to assay the temporal mRNA expression of BMP2 in relation to the CXCR4 chemokine receptor and its ligand, stromal derived factor 1 (SDF-1), since their expression has been shown to be associated with the systemic mobilization of mesenchymal and hemopoietic stem cells13,14 (Fig. 2). These results showed that BMP2 expression in the reamed bone had a bimodal pattern with peaks at 12 h (3.5-fold increase) and 7 days (2.6-fold increase; Fig. 2). The expression in the contralateral tibias showed a different bimodal temporal pattern of expression with peaks at 2 h (2.2-fold increase) and 14 days (2.2-fold increase). The analysis of the CXCR4 receptor in the reamed limb showed an almost identical profile both in its scale of induction and temporal profile to that of BMP2 while in the contralateral limb the early peak showed good correspondence at later times, CXCR4 expression peaked a week after BMP2 expression. Interestingly, CXCR4 showed divergent expression from BMP2 at 21 days after reaming and showed increased expression in both the contralateral and reamed bones. SDF-1 expression showed good correspondence to BMP2 expression in the injured limb only for its later peak of expression, while SDF-1 expression was similar to that of its receptor in the contralateral limb. It is also interesting to note that overall the expression of SDF-1 was greater in the uninjured limb than in the injured limb. As a control, TGF-β1 was examined in this analysis, since previous studies had shown that it was involved in the local recruitment of mesenchymal stem recruitment during the coupled remodeling of bone.15 It is interesting to note that unlike CXCR4 and SDF-1 expression which showed systemic induction after trauma, TGF-β1 was induced immediately after reaming (2 h) in the uninjured limb and then at the 7 days peak concurrent with the initiation of coupled remodeling.


Skeletal trauma generates systemic BMP2 activation that is temporally related to the mobilization of CD73+ cells.

Marsell R, Steen B, Bais MV, Mortlock DP, Einhorn TA, Gerstenfeld LC - J. Orthop. Res. (2013)

Steady state mRNA expression of morphogens and markers associated with stem cell mobilization whole bone segments from the regions that had been reamed or comparable regions from contralateral and control bones as described in Materials and Methods Section, were used for these studies. qRT-PCR analysis was made for RNAs from (Reamed) bones compared to the (Contralateral) of the traumatized mice and from uninjured mice (Naïve Control) tibia. Data are displayed as fold change versus Naïve Control set as base line (=1). Time after surgery and the nature of each mRNA that was examined is denoted in the figure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263190&req=5

fig02: Steady state mRNA expression of morphogens and markers associated with stem cell mobilization whole bone segments from the regions that had been reamed or comparable regions from contralateral and control bones as described in Materials and Methods Section, were used for these studies. qRT-PCR analysis was made for RNAs from (Reamed) bones compared to the (Contralateral) of the traumatized mice and from uninjured mice (Naïve Control) tibia. Data are displayed as fold change versus Naïve Control set as base line (=1). Time after surgery and the nature of each mRNA that was examined is denoted in the figure.
Mentions: The systemic nature of BMP2 expression after trauma led us to hypothesize that there would be increased hematopoietic and/or mesenchymal stem cell mobilization throughout the skeleton. In order to test this hypothesis, we chose to assay the temporal mRNA expression of BMP2 in relation to the CXCR4 chemokine receptor and its ligand, stromal derived factor 1 (SDF-1), since their expression has been shown to be associated with the systemic mobilization of mesenchymal and hemopoietic stem cells13,14 (Fig. 2). These results showed that BMP2 expression in the reamed bone had a bimodal pattern with peaks at 12 h (3.5-fold increase) and 7 days (2.6-fold increase; Fig. 2). The expression in the contralateral tibias showed a different bimodal temporal pattern of expression with peaks at 2 h (2.2-fold increase) and 14 days (2.2-fold increase). The analysis of the CXCR4 receptor in the reamed limb showed an almost identical profile both in its scale of induction and temporal profile to that of BMP2 while in the contralateral limb the early peak showed good correspondence at later times, CXCR4 expression peaked a week after BMP2 expression. Interestingly, CXCR4 showed divergent expression from BMP2 at 21 days after reaming and showed increased expression in both the contralateral and reamed bones. SDF-1 expression showed good correspondence to BMP2 expression in the injured limb only for its later peak of expression, while SDF-1 expression was similar to that of its receptor in the contralateral limb. It is also interesting to note that overall the expression of SDF-1 was greater in the uninjured limb than in the injured limb. As a control, TGF-β1 was examined in this analysis, since previous studies had shown that it was involved in the local recruitment of mesenchymal stem recruitment during the coupled remodeling of bone.15 It is interesting to note that unlike CXCR4 and SDF-1 expression which showed systemic induction after trauma, TGF-β1 was induced immediately after reaming (2 h) in the uninjured limb and then at the 7 days peak concurrent with the initiation of coupled remodeling.

Bottom Line: Stem cell mobilization was analyzed by FACS analysis using CD73, a marker associated with bone marrow stromal stem cells.A ∼20% increase of CD73 positive cells was seen in the peripheral blood 2 days after reaming.These data showed that traumatic bone injury caused a systemic induction of BMP2 expression and that this increase is correlated with the mobilization of CD73 positive cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, Boston University Medical Center, 715 Albany Street, R-205, Boston, 02118, Massachusetts.

Show MeSH
Related in: MedlinePlus