Pten knockout in mouse preosteoblasts leads to changes in bone turnover and strength.
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Pten knockout in mouse preosteoblasts leads to changes in bone turnover and strength. / Lorenz, Judith; Richter, Sandy; Kirstein, Anna S; Kolbig, Florentien; Nebe, Michele; Schulze, Marco; Kiess, Wieland; Spitzbarth, Ingo; Kloting, Nora; Le Duc, Diana; Baschant, Ulrike; Garten, Antje.
In: JBMR Plus, Vol. 8, No. 3, ziad016, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Pten knockout in mouse preosteoblasts leads to changes in bone turnover and strength.
AU - Lorenz, Judith
AU - Richter, Sandy
AU - Kirstein, Anna S
AU - Kolbig, Florentien
AU - Nebe, Michele
AU - Schulze, Marco
AU - Kiess, Wieland
AU - Spitzbarth, Ingo
AU - Kloting, Nora
AU - Le Duc, Diana
AU - Baschant, Ulrike
AU - Garten, Antje
PY - 2024
Y1 - 2024
N2 - Bone development and remodeling are controlled by the phosphoinositide-3-kinase (Pi3k) signaling pathway. We investigated the effects of downregulation of phosphatase and tensin homolog (Pten), a negative regulator of Pi3k signaling, in a mouse model of Pten deficiency in preosteoblasts. We aimed to identify mechanisms that are involved in the regulation of bone turnover and are linked to bone disorders. Femora, tibiae, and bone marrow stromal cells (BMSCs) isolated from mice with a conditional deletion of Pten (Pten cKO) in Osterix/Sp7-expressing osteoprogenitor cells were compared to Cre-negative controls. Bone phenotyping was performed by muCT measurements, bone histomorphometry, quantification of bone turnover markers CTX and procollagen type 1N propeptide (P1NP), and three-point bending test. Proliferation of BMSCs was measured by counting nuclei and Ki-67-stained cells. In vitro, osteogenic differentiation capacity was determined by ALP staining, as well as by detecting gene expression of osteogenic markers. BMSCs from Pten cKO mice were functionally different from control BMSCs. Osteogenic markers were increased in BMSCs derived from Pten cKO mice, while Pten protein expression was lower and Akt phosphorylation was increased. We detected a higher trabecular bone volume and an altered cortical bone morphology in Pten cKO bones with a progressive decrease in bone and tissue mineral density. Pten cKO bones displayed fewer osteoclasts and more osteoblasts (P=.00095) per trabecular bone surface and a higher trabecular bone formation rate. Biomechanical analysis revealed a significantly higher bone strength (P=.00012 for males) and elasticity of Pten cKO femora. On the cellular level, both proliferation and osteogenic differentiation capacity of Pten cKO BMSCs were significantly increased compared to controls. Our findings suggest that Pten knockout in osteoprogenitor cells increases bone stability and elasticity by increasing trabecular bone mass and leads to increased proliferation and osteogenic differentiation of BMSCs.
AB - Bone development and remodeling are controlled by the phosphoinositide-3-kinase (Pi3k) signaling pathway. We investigated the effects of downregulation of phosphatase and tensin homolog (Pten), a negative regulator of Pi3k signaling, in a mouse model of Pten deficiency in preosteoblasts. We aimed to identify mechanisms that are involved in the regulation of bone turnover and are linked to bone disorders. Femora, tibiae, and bone marrow stromal cells (BMSCs) isolated from mice with a conditional deletion of Pten (Pten cKO) in Osterix/Sp7-expressing osteoprogenitor cells were compared to Cre-negative controls. Bone phenotyping was performed by muCT measurements, bone histomorphometry, quantification of bone turnover markers CTX and procollagen type 1N propeptide (P1NP), and three-point bending test. Proliferation of BMSCs was measured by counting nuclei and Ki-67-stained cells. In vitro, osteogenic differentiation capacity was determined by ALP staining, as well as by detecting gene expression of osteogenic markers. BMSCs from Pten cKO mice were functionally different from control BMSCs. Osteogenic markers were increased in BMSCs derived from Pten cKO mice, while Pten protein expression was lower and Akt phosphorylation was increased. We detected a higher trabecular bone volume and an altered cortical bone morphology in Pten cKO bones with a progressive decrease in bone and tissue mineral density. Pten cKO bones displayed fewer osteoclasts and more osteoblasts (P=.00095) per trabecular bone surface and a higher trabecular bone formation rate. Biomechanical analysis revealed a significantly higher bone strength (P=.00012 for males) and elasticity of Pten cKO femora. On the cellular level, both proliferation and osteogenic differentiation capacity of Pten cKO BMSCs were significantly increased compared to controls. Our findings suggest that Pten knockout in osteoprogenitor cells increases bone stability and elasticity by increasing trabecular bone mass and leads to increased proliferation and osteogenic differentiation of BMSCs.
U2 - 10.1093/jbmrpl/ziad016
DO - 10.1093/jbmrpl/ziad016
M3 - Journal article
C2 - 38505222
VL - 8
JO - JBMR Plus
JF - JBMR Plus
SN - 2473-4039
IS - 3
M1 - ziad016
ER -
ID: 386303347