ESPE2021 ePoster Category 2 Bone, growth plate and mineral metabolism (41 abstracts)
PTEN downregulation in mouse osteoprogenitor cells impacts on bone stability and turnover
Judith Lorenz 1 , Anna Kirstein 1 , Michѐle Nebe 1 , Sandy Richter 1 , Diana Le Duc 2 , Wieland Kiess 1 , Nora Klöting-Blüher 3 , Ulrike Baschant 4 & Antje Garten 1
1Hospital for Children and Adolescents, Leipzig University, Leipzig, Germany; 2Institute of Human Genetics, Leipzig University, Leipzig, Germany; 3Helmholtz Institute for Metabolic, Obesity and Vascular Research, Leipzig University, Leipzig, Germany; 4Bone Lab, University Hospital Carl Gustav Carus, Dresden, Germany
Background: Signaling through the phosphoinositid-3-kinase (PI3K) pathway modulates bone development and remodeling. We aimed to dissect the role of phosphatase and tensin homolog (Pten), a negative regulator of PI3K signaling, in osteoprogenitor cells.
Methods: Femura, tibiae and bone marrow stromal cells (BMSCs) from mice with Cre-inducible Pten knockdown in cells expressing the transcription factor Osterix (Pten cKO) and Cre negative control mice were compared. Bone phenotyping was performed by µCT and 3-point bending test. Number of osteoclasts and osteoblasts was determined by tartrate resistant acid phosphatase (TRAP) immunohistochemistry, bone marrow fat was quantified by osmium staining. Proliferation of BMSCs was measured by counting Hoechst and Ki-67 stained cells, adipogenic and osteogenic differentiation was determined by Oil Red O lipid and alkaline phosphatase staining, respectively.
Results: We detected a higher trabecular bone volume/total volume (BV/TV) and higher bone mineral density (BMD) in Pten cKO of both sexes, while BV/TV and BMD was lower in cortical bone. Biomechanical analysis revealed a significantly higher maximum force (3.7fold, P = 0.0003 for males) and elasticity of Pten cKO femura. There were less osteoclasts (0.7 fold) and more osteoblasts (2.0fold, P = 0.0006) per bone surface in bones from male Pten cKO mice compared to controls. Serum markers for bone turnover (P1NP and CTX) were significantly increased both in Pten cKO male and female mice. The percentage of bone marrow fat was higher in male (1.4fold, p = 0.007), but not female Pten cKO mice compared to controls. An increase in proliferation for male (1.8fold), but not female BMSCs from Pten cKO compared to controls was detected. While there was no significant difference in adipogenic differentiation in vitro, osteogenic differentiation capacity was significantly enhanced in BMSCs from both male and female Pten cKO mice.
Conclusion: Pten downregulation in Osterix-expressing osteoprogenitor cells increases bone stability and elasticity and leads to increased proliferation and osteogenic differentiation.
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