NMP4, an Arbiter of Bone Cell Secretory Capacity and Regulator of Skeletal Response to PTH Therapy.
Induced bone anabolism
Osteoanabolics
Osteoporosis
Scaling factor
Secretory cells
The unfolded protein response (UPR)
Journal
Calcified tissue international
ISSN: 1432-0827
Titre abrégé: Calcif Tissue Int
Pays: United States
ID NLM: 7905481
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
31
01
2023
accepted:
21
04
2023
pmc-release:
01
07
2024
medline:
10
7
2023
pubmed:
6
5
2023
entrez:
5
5
2023
Statut:
ppublish
Résumé
The skeleton is a secretory organ, and the goal of some osteoporosis therapies is to maximize bone matrix output. Nmp4 encodes a novel transcription factor that regulates bone cell secretion as part of its functional repertoire. Loss of Nmp4 enhances bone response to osteoanabolic therapy, in part, by increasing the production and delivery of bone matrix. Nmp4 shares traits with scaling factors, which are transcription factors that influence the expression of hundreds of genes to govern proteome allocation for establishing secretory cell infrastructure and capacity. Nmp4 is expressed in all tissues and while global loss of this gene leads to no overt baseline phenotype, deletion of Nmp4 has broad tissue effects in mice challenged with certain stressors. In addition to an enhanced response to osteoporosis therapies, Nmp4-deficient mice are less sensitive to high fat diet-induced weight gain and insulin resistance, exhibit a reduced disease severity in response to influenza A virus (IAV) infection, and resist the development of some forms of rheumatoid arthritis. In this review, we present the current understanding of the mechanisms underlying Nmp4 regulation of the skeletal response to osteoanabolics, and we discuss how this unique gene contributes to the diverse phenotypes among different tissues and stresses. An emerging theme is that Nmp4 is important for the infrastructure and capacity of secretory cells that are critical for health and disease.
Identifiants
pubmed: 37147466
doi: 10.1007/s00223-023-01088-x
pii: 10.1007/s00223-023-01088-x
pmc: PMC10330242
mid: NIHMS1899979
doi:
Substances chimiques
Parathyroid Hormone
0
Transcription Factors
0
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
110-125Subventions
Organisme : BLRD VA
ID : I01 BX001733
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR073739
Pays : United States
Organisme : BLRD VA
ID : I01 BX005861
Pays : United States
Organisme : BLRD VA
ID : IK6 BX003783
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR053237
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR065971
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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