BONE HOMEOSTASIS IS SIGNIFICANTLY ALTERED IN A MYELODYSPLASTIC SYNDROME MOUSE MODEL
(Abstract release date: 05/19/16)
EHA Library. Weidner H. 06/09/16; 132744; E1195
Ms. Heike Weidner
Contributions
Contributions
Abstract
Abstract: E1195
Type: Eposter Presentation
Background
Myelodysplastic syndromes (MDS) are diseases of the elderly characterized by an ineffective hematopoiesis leading to cytopenias. Increasing evidence suggests a role of the bone microenvironment in influencing the development and progression of MDS. However, the underlying mechanisms are not fully understood. NUP98-HOXD13 (NHD13) mice develop MDS-like symptoms at an age of 6 months, including anemia and an increased number of blasts in the bone marrow. Thus, it is a suitable model to study bone homeostasis in the setting of MDS.
Aims
Here, we assessed bone homeostasis in NHD13 mice before (2 months of age) and after (6 months of age) the onset of MDS.
Methods
Micro-computed tomography was performed using the femurs of 2- and 6-month-old male NHD13 and wild-type mice. Bone samples were then histologically stained for the osteoclast marker tartrate-resistant acid phosphatase (TRAP). The bone formation rate was assessed using dual calcein labeling. In addition, serum was analyzed by ELISAs to assess the bone turnover markers C-terminal telopeptide of type I collagen (CTX-I) and procollagen type I propeptide (P1NP).
Results
At 2 months of age NHD13 mice had not yet developed any cytopenia. Nevertheless, there was already an apparent alteration of bone homeostasis. The trabecular bone volume (BV/TV) [-26%; P<.05] and trabecular number (Tb.N) [-20%; P<.01] were reduced in the femurs of NHD13 compared to wild-type mice. Serum markers indicated an increased bone turnover in NHD13 mice [P1NP 4-fold, P<.01; +17% CTX). At the age of 6 months the NHD13 mice had developed anemia indicated by a reduced hematocrit, -17%, P<.001. BV/TV in these mice was unchanged when compared with those of wild-type mice. Of interest, the number of trabeculae was reduced in the 6-month-old NHD13 mice [-15%; P<.001] whereas their thickness was increased [+18%; P<.01], suggesting increased osteoblast activity. In fact, histology indicated an increase in the osteoblast surface in the femurs from NHD13 by 10% [P<.01] and also the bone formation marker P1NP was elevated in the serum by 54% [P<.05] compared to wild-type mice. Although NHD13 mice had a lower osteoclast-covered surface on the bone [-78%; P<.01], the bone resorption marker CTX-I was increased by 32% [P<.05].
Conclusion
NHD13 mice show an altered bone homeostasis, which is characterized by a high bone turnover. This is in line with an abnormal interaction of dysplastic hematopoietic cells with the bone compartment.
Session topic: E-poster
Keyword(s): Bone microenvironment, Mouse model, Myelodysplasia, NUP98
Type: Eposter Presentation
Background
Myelodysplastic syndromes (MDS) are diseases of the elderly characterized by an ineffective hematopoiesis leading to cytopenias. Increasing evidence suggests a role of the bone microenvironment in influencing the development and progression of MDS. However, the underlying mechanisms are not fully understood. NUP98-HOXD13 (NHD13) mice develop MDS-like symptoms at an age of 6 months, including anemia and an increased number of blasts in the bone marrow. Thus, it is a suitable model to study bone homeostasis in the setting of MDS.
Aims
Here, we assessed bone homeostasis in NHD13 mice before (2 months of age) and after (6 months of age) the onset of MDS.
Methods
Micro-computed tomography was performed using the femurs of 2- and 6-month-old male NHD13 and wild-type mice. Bone samples were then histologically stained for the osteoclast marker tartrate-resistant acid phosphatase (TRAP). The bone formation rate was assessed using dual calcein labeling. In addition, serum was analyzed by ELISAs to assess the bone turnover markers C-terminal telopeptide of type I collagen (CTX-I) and procollagen type I propeptide (P1NP).
Results
At 2 months of age NHD13 mice had not yet developed any cytopenia. Nevertheless, there was already an apparent alteration of bone homeostasis. The trabecular bone volume (BV/TV) [-26%; P<.05] and trabecular number (Tb.N) [-20%; P<.01] were reduced in the femurs of NHD13 compared to wild-type mice. Serum markers indicated an increased bone turnover in NHD13 mice [P1NP 4-fold, P<.01; +17% CTX). At the age of 6 months the NHD13 mice had developed anemia indicated by a reduced hematocrit, -17%, P<.001. BV/TV in these mice was unchanged when compared with those of wild-type mice. Of interest, the number of trabeculae was reduced in the 6-month-old NHD13 mice [-15%; P<.001] whereas their thickness was increased [+18%; P<.01], suggesting increased osteoblast activity. In fact, histology indicated an increase in the osteoblast surface in the femurs from NHD13 by 10% [P<.01] and also the bone formation marker P1NP was elevated in the serum by 54% [P<.05] compared to wild-type mice. Although NHD13 mice had a lower osteoclast-covered surface on the bone [-78%; P<.01], the bone resorption marker CTX-I was increased by 32% [P<.05].
Conclusion
NHD13 mice show an altered bone homeostasis, which is characterized by a high bone turnover. This is in line with an abnormal interaction of dysplastic hematopoietic cells with the bone compartment.
Session topic: E-poster
Keyword(s): Bone microenvironment, Mouse model, Myelodysplasia, NUP98
Abstract: E1195
Type: Eposter Presentation
Background
Myelodysplastic syndromes (MDS) are diseases of the elderly characterized by an ineffective hematopoiesis leading to cytopenias. Increasing evidence suggests a role of the bone microenvironment in influencing the development and progression of MDS. However, the underlying mechanisms are not fully understood. NUP98-HOXD13 (NHD13) mice develop MDS-like symptoms at an age of 6 months, including anemia and an increased number of blasts in the bone marrow. Thus, it is a suitable model to study bone homeostasis in the setting of MDS.
Aims
Here, we assessed bone homeostasis in NHD13 mice before (2 months of age) and after (6 months of age) the onset of MDS.
Methods
Micro-computed tomography was performed using the femurs of 2- and 6-month-old male NHD13 and wild-type mice. Bone samples were then histologically stained for the osteoclast marker tartrate-resistant acid phosphatase (TRAP). The bone formation rate was assessed using dual calcein labeling. In addition, serum was analyzed by ELISAs to assess the bone turnover markers C-terminal telopeptide of type I collagen (CTX-I) and procollagen type I propeptide (P1NP).
Results
At 2 months of age NHD13 mice had not yet developed any cytopenia. Nevertheless, there was already an apparent alteration of bone homeostasis. The trabecular bone volume (BV/TV) [-26%; P<.05] and trabecular number (Tb.N) [-20%; P<.01] were reduced in the femurs of NHD13 compared to wild-type mice. Serum markers indicated an increased bone turnover in NHD13 mice [P1NP 4-fold, P<.01; +17% CTX). At the age of 6 months the NHD13 mice had developed anemia indicated by a reduced hematocrit, -17%, P<.001. BV/TV in these mice was unchanged when compared with those of wild-type mice. Of interest, the number of trabeculae was reduced in the 6-month-old NHD13 mice [-15%; P<.001] whereas their thickness was increased [+18%; P<.01], suggesting increased osteoblast activity. In fact, histology indicated an increase in the osteoblast surface in the femurs from NHD13 by 10% [P<.01] and also the bone formation marker P1NP was elevated in the serum by 54% [P<.05] compared to wild-type mice. Although NHD13 mice had a lower osteoclast-covered surface on the bone [-78%; P<.01], the bone resorption marker CTX-I was increased by 32% [P<.05].
Conclusion
NHD13 mice show an altered bone homeostasis, which is characterized by a high bone turnover. This is in line with an abnormal interaction of dysplastic hematopoietic cells with the bone compartment.
Session topic: E-poster
Keyword(s): Bone microenvironment, Mouse model, Myelodysplasia, NUP98
Type: Eposter Presentation
Background
Myelodysplastic syndromes (MDS) are diseases of the elderly characterized by an ineffective hematopoiesis leading to cytopenias. Increasing evidence suggests a role of the bone microenvironment in influencing the development and progression of MDS. However, the underlying mechanisms are not fully understood. NUP98-HOXD13 (NHD13) mice develop MDS-like symptoms at an age of 6 months, including anemia and an increased number of blasts in the bone marrow. Thus, it is a suitable model to study bone homeostasis in the setting of MDS.
Aims
Here, we assessed bone homeostasis in NHD13 mice before (2 months of age) and after (6 months of age) the onset of MDS.
Methods
Micro-computed tomography was performed using the femurs of 2- and 6-month-old male NHD13 and wild-type mice. Bone samples were then histologically stained for the osteoclast marker tartrate-resistant acid phosphatase (TRAP). The bone formation rate was assessed using dual calcein labeling. In addition, serum was analyzed by ELISAs to assess the bone turnover markers C-terminal telopeptide of type I collagen (CTX-I) and procollagen type I propeptide (P1NP).
Results
At 2 months of age NHD13 mice had not yet developed any cytopenia. Nevertheless, there was already an apparent alteration of bone homeostasis. The trabecular bone volume (BV/TV) [-26%; P<.05] and trabecular number (Tb.N) [-20%; P<.01] were reduced in the femurs of NHD13 compared to wild-type mice. Serum markers indicated an increased bone turnover in NHD13 mice [P1NP 4-fold, P<.01; +17% CTX). At the age of 6 months the NHD13 mice had developed anemia indicated by a reduced hematocrit, -17%, P<.001. BV/TV in these mice was unchanged when compared with those of wild-type mice. Of interest, the number of trabeculae was reduced in the 6-month-old NHD13 mice [-15%; P<.001] whereas their thickness was increased [+18%; P<.01], suggesting increased osteoblast activity. In fact, histology indicated an increase in the osteoblast surface in the femurs from NHD13 by 10% [P<.01] and also the bone formation marker P1NP was elevated in the serum by 54% [P<.05] compared to wild-type mice. Although NHD13 mice had a lower osteoclast-covered surface on the bone [-78%; P<.01], the bone resorption marker CTX-I was increased by 32% [P<.05].
Conclusion
NHD13 mice show an altered bone homeostasis, which is characterized by a high bone turnover. This is in line with an abnormal interaction of dysplastic hematopoietic cells with the bone compartment.
Session topic: E-poster
Keyword(s): Bone microenvironment, Mouse model, Myelodysplasia, NUP98
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