Neuropeptide Y1 receptor antagonist promotes osteoporosis and microdamage repair and enhances osteogenic differentiation of bone marrow stem cells via cAMP/PKA/CREB pathway.
Aged
Animals
Arginine
/ analogs & derivatives
Bone Marrow Cells
/ metabolism
Cell Differentiation
Cyclic AMP
/ metabolism
Cyclic AMP Response Element-Binding Protein
/ metabolism
Down-Regulation
Female
Humans
Male
Osteogenesis
/ drug effects
Osteoporosis
/ diagnosis
Rats
Receptors, Neuropeptide Y
/ antagonists & inhibitors
X-Ray Microtomography
bone marrow stromal cells
bone mcirodamage
bone microstructure
neuropeptide Y
osteoporosis
Journal
Aging
ISSN: 1945-4589
Titre abrégé: Aging (Albany NY)
Pays: United States
ID NLM: 101508617
Informations de publication
Date de publication:
07 05 2020
07 05 2020
Historique:
received:
13
12
2019
accepted:
30
03
2020
pubmed:
10
5
2020
medline:
26
2
2021
entrez:
9
5
2020
Statut:
ppublish
Résumé
Osteoporosis is a common metabolic bone disorder in the elderly population. The accumulation of bone microdamage is a critical factor of osteoporotic fracture. Neuropeptide Y (NPY) has been reported to regulated bone metabolism through Y1 receptor (Y1R). In this study the effects and mechanisms of Y1R antagonist on prevention for osteoporosis were characterized. In the clinical experiment, compared with osteoarthritis (OA), osteoporosis (OP) showed significant osteoporotic bone microstructure and accumulation of bone microdamage. NPY and Y1R immunoreactivity in bone were stronger in OP group, and were both correlated with bone volume fraction (BV/TV). In vivo experiment, Y1R antagonist significantly improved osteoporotic microstructure in the ovariectomized (OVX) rats. And Y1R antagonist promoted RUNX2, OPG and inhibit RANKL, MMP9 in bone marrow. In vitro cell culture experiment, NPY inhibited osteogenesis, elevated RANKL/OPG ratio and downregulated the expression of cAMP, p-PKAs and p-CREB in BMSCs, treated with Y1R antagonist or 8-Bromo-cAMP could inhibit the effects of NPY. Together, Y1R antagonist improved the bone microstructure and reduced bone microdamage in OVX rats. NPY-Y1R could inhibit osteoblast differentiation of BMSCs via cAMP/PKA/CREB pathway. Our findings highlight the regulation of NPY-Y1R in bone metabolism as a potential therapy strategy for the prevention of osteoporosis and osteoporotic fracture.
Identifiants
pubmed: 32381754
pii: 103129
doi: 10.18632/aging.103129
pmc: PMC7244071
doi:
Substances chimiques
Cyclic AMP Response Element-Binding Protein
0
Receptors, Neuropeptide Y
0
neuropeptide Y-Y1 receptor
0
Arginine
94ZLA3W45F
Cyclic AMP
E0399OZS9N
BIBO 3304
O35HK034KO
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8120-8136Références
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