Withdrawal of parathyroid hormone after prolonged administration leads to adipogenic differentiation of mesenchymal precursors in vivo.
Lineage tracing
Osteoblast precursor
Parathyroid hormone
Stem cell
Stromal cell
Journal
Bone
ISSN: 1873-2763
Titre abrégé: Bone
Pays: United States
ID NLM: 8504048
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
29
03
2018
revised:
19
05
2018
accepted:
21
05
2018
pubmed:
26
5
2018
medline:
24
1
2020
entrez:
26
5
2018
Statut:
ppublish
Résumé
Intermittent PTH-like drugs are the only approved so-called anabolic agent that increases bone mass in both mice and humans. It is well documented that PTH targets mature cells of the osteoblast lineage, with only indirect evidence of its actions on early cells of the osteoblast lineage. Using a triple transgenic mouse model that allowed labeling of very early cells of the osteoblast lineage, we traced the progeny of these into osteoblast lineage in adult mice. These early cells expressed PTH1R and multiplied when PTH (1-34) was administered daily. We also showed that the early mesenchymal cells showed accelerated differentiation into mature osteocalcin-positive osteoblasts and osteocytes. Rather surprisingly, when teriparatide administration was stopped, these early mesenchymal precursors differentiated into adipocytes. We showed that the adipogenic differentiation is accompanied by a decrease in wnt signaling in osteoblast precursors. In this review, we discuss the possible clinical relevance of this finding and the possible molecular mechanisms that contribute to this phenotype in vivo.
Identifiants
pubmed: 29800694
pii: S8756-3282(18)30214-X
doi: 10.1016/j.bone.2018.05.024
pmc: PMC6250592
mid: NIHMS971491
pii:
doi:
Substances chimiques
Parathyroid Hormone
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
16-19Subventions
Organisme : NIDDK NIH HHS
ID : P01 DK011794
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR066261
Pays : United States
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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