Absence of p21(WAF1/CIP1/SDI1) protects against osteopenia and minimizes bone loss after ovariectomy in a mouse model.
Animals
Bone Diseases, Metabolic
/ diagnostic imaging
Bone Remodeling
/ genetics
Cyclin-Dependent Kinase Inhibitor p21
/ deficiency
Disease Models, Animal
Female
Humans
Mesenchymal Stem Cells
/ metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Osteoblasts
/ metabolism
Osteoclasts
/ metabolism
Osteoporosis, Postmenopausal
/ prevention & control
Ovariectomy
/ adverse effects
X-Ray Microtomography
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
13
11
2018
accepted:
25
03
2019
entrez:
11
4
2019
pubmed:
11
4
2019
medline:
3
1
2020
Statut:
epublish
Résumé
p21(WAF1/CIP1/SDI1) is a critical sentinel of the cell cycle that plays an important role in determining cell fate with respect to proliferation, differentiation and apoptosis. Recent studies have demonstrated that inhibition/loss of p21 promotes osteo-chondro differentiation in progenitor/stem cells, and that p21 knockout (p21-/-) mice demonstrate enhanced bone regeneration compared to wild-type controls after a non-critical size defect. It was therefore hypothesized that the absence of p21 may also protect against bone loss through enhancing bone formation, tilting the balance away from bone resorption, in an ovariectomy-induced osteopenia mouse model, investigated via microCT imaging. While p21-/- mice demonstrated significantly less bone loss after ovariectomy compared to wild-type controls, no increase in the number osteoclasts or osteoblasts in the bone or bone marrow was observed, nor was there an increase in osteoclast activity. Therefore, while the absence of p21 protected mice against estrogen mediated bone loss, the mechanisms/pathways responsible remained elusive. This study demonstrates that p21 may play a significant role in bone remodeling, and a better understanding of how the p21 pathway regulates bone anabolism and catabolism could lead to novel therapies for osteoporosis in the future.
Identifiants
pubmed: 30970032
doi: 10.1371/journal.pone.0215018
pii: PONE-D-18-32144
pmc: PMC6457871
doi:
Substances chimiques
Cdkn1a protein, mouse
0
Cyclin-Dependent Kinase Inhibitor p21
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0215018Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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