Deletion of protein kinase D1 in osteoprogenitor cells results in decreased osteogenesis in vitro and reduced bone mineral density in vivo
| Autor: | Yun Su, Qing Zhong, Jianrui Xu, Vivek Choudhary, Meghan E. McGee-Lawrence, Mohammed Elsalanty, Ranya Elsayed, Xingming Shi, Wendy B. Bollag, Lakiea Bailey, Kanglun Yu, Kehong Ding, Maribeth H. Johnson, Carlos M. Isales |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Bone density Bone Marrow Cells Mice Transgenic Biochemistry Article Adenoviridae 03 medical and health sciences 0302 clinical medicine Endocrinology Calcification Physiologic In vivo Bone Density Osteogenesis Internal medicine Conditional gene knockout medicine Animals Amino Acids Molecular Biology Protein Kinase C Bone mineral Integrases Chemistry Stem Cells Mesenchymal stem cell Mesenchymal Stem Cells Alkaline Phosphatase In vitro 030104 developmental biology 030220 oncology & carcinogenesis Protein kinase D1 Stem cell Gene Deletion |
| Zdroj: | Molecular and cellular endocrinology. 461 |
| ISSN: | 1872-8057 |
| Popis: | Protein kinase D1 (PRKD1) is thought to play a role in a number of cellular functions, including proliferation and differentiation. We hypothesized that PRKD1 in bone marrow-derived mesenchymal stem cells (BMMSC) could modulate osteogenesis. In BMMSCs from floxed PRKD1 mice, PRKD1 ablation with adenovirus-mediated Cre-recombinase expression inhibited BMMSC differentiation in vitro. In 3- and 6-month-old conditional knockout mice (cKO), in which PRKD1 was ablated in osteoprogenitor cells by osterix promoter-driven Cre-recombinase, bone mineral density (BMD) was significantly reduced compared with floxed control littermates. Microcomputed tomography analysis also demonstrated a decrease in trabecular thickness and bone volume fraction in cKO mice at these ages. Dynamic bone histomorphometry suggested a mineralization defect in the cKO mice. However, by 9 months of age, the bone appeared to compensate for the lack of PRKD1, and BMD was not different. Taken together, these results suggest a potentially important role for PRKD1 in bone formation. |
| Databáze: | OpenAIRE |
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