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Inactivation of the Progesterone Receptor in Mx1+ Cells Potentiates Osteogenesis in Calvaria but Not in Long Bone.
- Source :
-
PloS one [PLoS One] 2015 Oct 02; Vol. 10 (10), pp. e0139490. Date of Electronic Publication: 2015 Oct 02 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- The effect of progesterone on bone remains elusive. We previously reported that global progesterone receptor (PR) knockout mice displayed high bone mass phenotype, suggesting that PR influences bone growth and modeling. Recently, Mx1+ cells were characterized to be mesenchymal stem cell-like pluripotent Cells. The aim of this study was to evaluate whether the PR in Mx1+ cells regulates osteogenesis. Using the Mx1-Cre;mT/mG reporter mouse model, we found that the calvarial cells exhibited minimal background Mx1-Cre activity prior to Cre activation by IFNα treatment as compared to the bone marrow stromal cells. IFNα treatment significantly activated Mx1-Cre in the calvarial cells. When the PR gene was deleted in the Mx1-Cre;PR-flox calvarial cells in vitro, significantly higher levels of expression of osteoblast maturation marker genes (RUNX2, Osteocalcin, and Dmp1) and osteogenic potential were detected. The PR-deficient calvariae exhibited greater bone volume, especially in the males. Although Mx1-Cre activity could be induced on the bone surface in vivo, the Mx1+ cells did not differentiate into osteocytes in long bones. Bone volumes at the distal femurs and the bone turnover marker serum Osteocalcin were similar between the Mx1-Cre;PR-flox mutant mice and the corresponding wild types in both sexes. In conclusion, our data demonstrates that blocking progesterone signaling via PRs in calvarial Mx1+ cells promoted osteoblast differentiation in the calvaria. Mx1+ was expressed by heterogeneous cells in bone marrow and did not differentiate into osteocyte during long bone development in vivo. Selectively inactivating the PR gene in Mx1+ cells affected the membrane bone formation but did not affect peripheral skeletal homeostasis.
- Subjects :
- Animals
Biomarkers
Bone Marrow pathology
Cells, Cultured
Chondrocytes pathology
Crosses, Genetic
Female
Gene Expression Regulation, Developmental
Genes, Reporter
Green Fluorescent Proteins analysis
Green Fluorescent Proteins biosynthesis
Green Fluorescent Proteins genetics
Growth Plate pathology
Integrases
Luminescent Proteins analysis
Luminescent Proteins biosynthesis
Luminescent Proteins genetics
Male
Mesenchymal Stem Cells metabolism
Mice
Mice, Transgenic
Organ Specificity
Osteogenesis drug effects
Pluripotent Stem Cells metabolism
Progesterone physiology
Receptors, Progesterone genetics
Receptors, Progesterone physiology
Recombinant Fusion Proteins metabolism
Sex Characteristics
Red Fluorescent Protein
Femur pathology
Gene Knockout Techniques
Interferon-alpha pharmacology
Mesenchymal Stem Cells cytology
Myxovirus Resistance Proteins genetics
Osteoblasts pathology
Osteogenesis physiology
Pluripotent Stem Cells cytology
Promoter Regions, Genetic drug effects
Receptors, Progesterone deficiency
Skull pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26431032
- Full Text :
- https://doi.org/10.1371/journal.pone.0139490