Kaempferol attenuates particle-induced osteogenic impairment by regulating ER stress via the IRE1α-XBP1s pathway.
J Biol Chem
; 300(6): 107394, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38768813
ABSTRACT
Periprosthetic osteolysis and subsequent aseptic loosening are the primary causes of failure following total joint arthroplasty. Wear particle-induced osteogenic impairment is recognized as an important contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress emerging as a pivotal underlying mechanism. Hence, searching for potential therapeutic targets and agents capable of modulating ER stress in osteoblasts is crucial for preventing aseptic loosening. Kaempferol (KAE), a natural flavonol compound, has shown promising osteoprotective effects and anti-ER stress properties in diverse diseases. However, the influence of KAE on ER stress-mediated osteogenic impairment induced by wear particles remains unclear. In this study, we observed that KAE effectively relieved TiAl6V4 particles-induced osteolysis by improving osteogenesis in a mouse calvarial model. Furthermore, we demonstrated that KAE could attenuate ER stress-mediated apoptosis in osteoblasts exposed to TiAl6V4 particles, both in vitro and in vivo. Mechanistically, our results revealed that KAE mitigated ER stress-mediated apoptosis by upregulating the IRE1α-XBP1s pathway while concurrently partially inhibiting the IRE1α-regulated RIDD and JNK activation. Collectively, our findings suggest that KAE is a prospective therapeutic agent for treating wear particle-induced osteolysis and highlight the IRE1α-XBP1s pathway as a potential therapeutic target for preventing aseptic loosening.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoblasts
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Osteogenesis
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Osteolysis
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Protein Serine-Threonine Kinases
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Kaempferols
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Endoribonucleases
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Endoplasmic Reticulum Stress
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X-Box Binding Protein 1
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
J Biol Chem
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: