RRC ID 58388
Author Yin Y, Corry KA, Loughran JP, Li J.
Title Moderate Nrf2 Activation by Genetic Disruption of Keap1 Has Sex-Specific Effects on Bone Mass in Mice.
Journal Sci Rep
Abstract Keap1 is a negative controller of the transcription factor Nrf2 for its activity. The Keap1/Nrf2 signaling pathway has been considered as a master regulator of cytoprotective genes, and exists in many cell types including osteoblasts and osteoclasts. Our previous study shows Nrf2 deletion decreases bone formation. Recent studies show hyperactivation of Nrf2 causes osteopenia in Keap1-/- mice, and Keap1-/- osteoblasts have significantly less proliferative potential than Keap1+/- osteoblasts. We aimed to examine if moderate Nrf2 activation by disruption of Keap1 impacts bone metabolism. We examined bone phenotype of Keap1 heterozygotic mice (Ht) in comparison with Keap1 wild type (WT) mice. Deletion or knockdown of Keap1 enhanced the gene expression of Nrf2, ALP and wnt5a in cultured primary osteoblasts compared to WT control. In male mice, compared with their age-matched littermate WT controls, Keap1 Ht mice showed significant increase in bone formation rate (+30.7%, P = 0.0029), but did not change the ultimate force (P < 0.01). The osteoclast cell numbers (-32.45%, P = 0.01) and surface (-32.58%, P = 0.03) were significantly reduced by Keap1 deficiency in male mice. Compared to male WT mice, serum bone resorption marker in male Keap1 Ht mice was significantly decreased. Our data suggest that moderate Nrf2 activation by disruption of Keap1 improved bone mass by regulating bone remodeling in male mice.
Volume 10(1)
Pages 348
Published 2020-1-15
DOI 10.1038/s41598-019-57185-1
PII 10.1038/s41598-019-57185-1
PMID 31941926
PMC PMC6962200
MeSH Animals Bone Density / physiology Bone Remodeling / genetics Bone Remodeling / physiology Bone and Bones / metabolism* Cells, Cultured Female Gene Knockdown Techniques Kelch-Like ECH-Associated Protein 1 / genetics Kelch-Like ECH-Associated Protein 1 / physiology* Male Mice Mice, Inbred C57BL NF-E2-Related Factor 2 / physiology* Osteoblasts / physiology Osteogenesis / genetics Osteogenesis / physiology* Sex Characteristics
IF 3.998
Times Cited 0
Mice RBRC01388