To register click here
Topic: Osteoblasts and bone formation
Nieminen-Pihala, Vappu(1)*;Rummukainen, Petri(1);Wang, Fan(1);Tarkkonen, Kati(1);Ivaska, Kaisa(1);Kiviranta, Riku(1);
(1)University of Turku- Institute of Biomedicine, Medical Biochemistry and Genetics, Turku, Finland;
Abstract Text
Background/introduction: Early B-cell factors (Ebfs) are a family of transcription factors regulating the differentiation of multiple cell types of mesenchymal origin, including osteoblasts. Global deletion of Ebf1 results in increased bone formation, while global loss of Ebf2 leads to enhanced bone resorption. Targeted deletion of Ebf1 in early committed osteoblasts leads to increased bone formation, whereas deletion in mature osteoblasts has no effect.
Purpose: To study the effects of Ebf2 specifically on long bone development and to investigate whether Ebf1 and Ebf2 co-operate in bone formation.
Methods: To target the effect of Ebf2 deletion more specifically to bone, we created a limb bud mesenchymal cell-specific Ebf2 knockout mouse model using Prrx1-Cre (Ebf2Prrx1). To study the possible interplay, we deleted both Ebf1 and Ebf2 in the cells expressing Prrx1 (Ebf1xEbf2Prrx1).
Results: Ebf2Prrx1 mice had a very mild bone phenotype. Deletion of both Ebf1 and Ebf2 in mesenchymal lineage cells led to a significant decrease in long bone length and an increase in both trabecular and cortical bone in females, while in males increased cortical bone mass and a growth plate defect was observed. Length of tibia was significantly reduced in Ebf1xEbf2Prrx1-/- males and females at six weeks of age. At 12 weeks, the reduction was even more pronounced in Ebf1xEbf2Prrx1-/- males (p<0.001) and females (p<0.001) when compared to controls. At 12 weeks there was a nearly 50% increase in the femur trabecular bone volume and trabecular number of Ebf1xEbf2Prrx1-/- females compared to controls.
Conclusions: We found that the conditional deletion of Ebf1 and Ebf2 in mesenchymal lineage cells leads to a significant, age-progressive bone phenotype. This phenotype is to some extent gender-dependent. Our data further verify that Ebfs modulate bone homeostasis and they are likely able to compensate for the lack of each other.
Topic: Osteoblasts and bone formation
Nieminen-Pihala, Vappu(1)*;Rummukainen, Petri(1);Wang, Fan(1);Tarkkonen, Kati(1);Ivaska, Kaisa(1);Kiviranta, Riku(1);
(1)University of Turku- Institute of Biomedicine, Medical Biochemistry and Genetics, Turku, Finland;
Abstract Text
Background/introduction: Early B-cell factors (Ebfs) are a family of transcription factors regulating the differentiation of multiple cell types of mesenchymal origin, including osteoblasts. Global deletion of Ebf1 results in increased bone formation, while global loss of Ebf2 leads to enhanced bone resorption. Targeted deletion of Ebf1 in early committed osteoblasts leads to increased bone formation, whereas deletion in mature osteoblasts has no effect.
Purpose: To study the effects of Ebf2 specifically on long bone development and to investigate whether Ebf1 and Ebf2 co-operate in bone formation.
Methods: To target the effect of Ebf2 deletion more specifically to bone, we created a limb bud mesenchymal cell-specific Ebf2 knockout mouse model using Prrx1-Cre (Ebf2Prrx1). To study the possible interplay, we deleted both Ebf1 and Ebf2 in the cells expressing Prrx1 (Ebf1xEbf2Prrx1).
Results: Ebf2Prrx1 mice had a very mild bone phenotype. Deletion of both Ebf1 and Ebf2 in mesenchymal lineage cells led to a significant decrease in long bone length and an increase in both trabecular and cortical bone in females, while in males increased cortical bone mass and a growth plate defect was observed. Length of tibia was significantly reduced in Ebf1xEbf2Prrx1-/- males and females at six weeks of age. At 12 weeks, the reduction was even more pronounced in Ebf1xEbf2Prrx1-/- males (p<0.001) and females (p<0.001) when compared to controls. At 12 weeks there was a nearly 50% increase in the femur trabecular bone volume and trabecular number of Ebf1xEbf2Prrx1-/- females compared to controls.
Conclusions: We found that the conditional deletion of Ebf1 and Ebf2 in mesenchymal lineage cells leads to a significant, age-progressive bone phenotype. This phenotype is to some extent gender-dependent. Our data further verify that Ebfs modulate bone homeostasis and they are likely able to compensate for the lack of each other.