Show simple item record

dc.contributor.authorVelletri, Tania
dc.contributor.authorHuang, Yin
dc.contributor.authorWang, Yu
dc.contributor.authorLi, Qing
dc.contributor.authorHu, Mingyuan
dc.contributor.authorXie, Ningxia
dc.contributor.authorYang, Qian
dc.contributor.authorChen, Xiaodong
dc.contributor.authorChen, Qing
dc.contributor.authorShou, Peishun
dc.contributor.authorGan, Yurun
dc.contributor.authorCandi, Eleonora
dc.contributor.authorMargherita, Annicchiarico-Petruzzelli
dc.contributor.authorAgostini, Massimiliano
dc.contributor.authorYang, Huilin
dc.contributor.authorMelino, Gerry
dc.contributor.authorShi, Yufang
dc.contributor.authorWang, Ying
dc.date.accessioned2021-01-07T16:23:44Z
dc.date.available2021-01-07T16:23:44Z
dc.date.issued2020-07-21
dc.date.submitted2019-12-19
dc.identifier.issn1350-9047
dc.identifier.others41418-020-0590-4
dc.identifier.other590
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/315840
dc.description.abstractAbstract: p53 plays a pivotal role in controlling the differentiation of mesenchymal stem cells (MSCs) by regulating genes involved in cell cycle and early steps of differentiation process. In the context of osteogenic differentiation of MSCs and bone homeostasis, the osteoprotegerin/receptor activator of NF-κB ligand/receptor activator of NF-κB (OPG/RANKL/RANK) axis is a critical signaling pathway. The absence or loss of function of p53 has been implicated in aberrant osteogenic differentiation of MSCs that results in higher bone formation versus erosion, leading to an unbalanced bone remodeling. Here, we show by microCT that mice with p53 deletion systemically or specifically in mesenchymal cells possess significantly higher bone density than their respective littermate controls. There is a negative correlation between p53 and OPG both in vivo by analysis of serum from p53+/+, p53+/−, and p53−/− mice and in vitro by p53 knockdown and ChIP assay in MSCs. Notably, high expression of Opg or its combination with low level of p53 are prominent features in clinical cancer lesion of osteosarcoma and prostate cancer respectively, which correlate with poor survival. Intra-bone marrow injection of prostate cancer cells, together with androgen can suppress p53 expression and enhance local Opg expression, leading to an enhancement of bone density. Our results support the notion that MSCs, as osteoblast progenitor cells and one major component of bone microenvironment, represent a cellular source of OPG, whose amount is regulated by the p53 status. It also highlights a key role for the p53-OPG axis in regulating the cancer associated bone remodeling.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/80
dc.subject/692/420
dc.subject/13/1
dc.subject/64/60
dc.subject/13/31
dc.subject/96/100
dc.subjectarticle
dc.titleLoss of p53 in mesenchymal stem cells promotes alteration of bone remodeling through negative regulation of osteoprotegerin
dc.typeArticle
dc.date.updated2021-01-07T16:23:43Z
prism.endingPage169
prism.issueIdentifier1
prism.publicationNameCell Death & Differentiation
prism.startingPage156
prism.volume28
dc.identifier.doi10.17863/CAM.62951
dcterms.dateAccepted2020-07-09
rioxxterms.versionofrecord10.1038/s41418-020-0590-4
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidHuang, Yin [0000-0001-5602-9871]
dc.contributor.orcidWang, Yu [0000-0002-7309-7304]
dc.contributor.orcidMelino, Gerry [0000-0001-9428-5972]
dc.contributor.orcidShi, Yufang [0000-0001-9716-2126]
dc.identifier.eissn1476-5403
pubs.funder-project-idMinistry of Science and Technology of the People’s Republic of China (Chinese Ministry of Science and Technology) (2018YFA0107500, 2018YFC1704300)
pubs.funder-project-idNational Natural Science Foundation of China (National Science Foundation of China) (81861138015, 31961133024, 31771641, 31601106, 81930085 and 81571612, 31601106)


Files in this item

Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)