.png){kind=icon}
.png){kind=icon}
Return
Isoorientin attenuates aging-induced bone deterioration by suppressing M1-mediated TLR4–MAPK–NF-κB inflammatory signaling
.png){kind=icon}
PRE
AI
J
J
A
W
Z
K
S
DOI：10.1007/s10522-026-10488-z.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Background: Aging disrupts bone remodeling by increasing osteoclast activity, reducing osteogenic capacity, and elevating inflammation. Toll-like receptor 4 (TLR4)–mediated inflammatory signaling has been implicated in bone degeneration, yet its role in age-related skeletal decline remains incompletely understood. Isoorientin, a plant-derived flavonoid with reported anti-inflammatory properties, has not been evaluated in the context of skeletal aging. Methods: Bone aging was first assessed in C57BL/6 J mice using micro-computed tomography (μCT), histology, TRAP staining, and immunofluorescence. The effects of isoorientin on osteogenesis were examined in senescent hBMSCs by alkaline phosphatase (ALP) activity, mineralization assays, and expression of osteogenesis-related genes. LPS-stimulated RAW264.7 cells were used to evaluate inflammatory responses and M1/M2 polarization. To assess TLR4/ mitogen-activated protein kinase (MAPK)/ nuclear factor-κB (NF-κB) regulation, RAW264.7 cells were treated with TAK-242 or TAK-242 plus isoorientin. Finally, aged mice were treated with isoorientin, TAK-242, or both to evaluate in vivo pathway modulation and bone protection. Results: Aged mice exhibited reduced trabecular mass, elevated osteoclast activity, and increased osteoclast-associated markers. Isoorientin treatment improved trabecular structure, decreased osteoclast numbers, and lowered osteoclast-associated proteins. In senescent hBMSCs, isoorientin restored ALP activity, enhanced mineral deposition, and increased osteogenic marker expression. Isoorientin also reduced pro-inflammatory cytokines, suppressed M1 polarization, and inhibited TLR4/MAPK/NF-κB activation. The combination of isoorientin and TAK-242 exhibited the most potent suppression of inflammatory signaling and the most significant enhancement in bone microarchitecture. Conclusion: Isoorientin alleviates age-related bone loss by suppressing TLR4-mediated inflammation, reducing osteoclast activation, and restoring impaired osteogenesis. These findings identify isoorientin as a promising therapeutic candidate for age-associated osteoporosis.
Keywords:
Isoorientin
Skeletal aging
TLR4 signaling
MAPK
NF-κB pathway
Journal
IF:
4.1
Papers:
1.7K
Citations:
3.5K
Organization
Cited Papers