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Geraniol-mediated osteoarthritis improvement by down-regulating PI3K/Akt/NF-κB and MAPK signals: In vivo and in vitro
Yifan Wu1, Zhanghong Wang2, Xin Fu1
1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Second School of Medicine, Wenzhou Medical University, 109, Xueyuanxi Road, Wenzhou, Zhejiang 325027, China; Bone Research Institute, The Key Orthopaedic Laboratory of Zhejiang Province, 109, Xueyuanxi Road, Wenzhou, Zhejiang 325027, China.
Abstract:
Osteoarthritis (OA) is a degenerative disease that has received increasing attention among the elderly. Its clinical manifestation is primarily long-term joint pain. Evidence for the pharmacological effects of geraniol in various diseases is accumulating. However, whether geraniol has a therapeutic effect against OA remains to be determined. In this study, we discussed the anti-inflammatory effects of geraniol in IL-1β-induced chondrocytes and the anti-cartilage degradation effects in a mouse model of destabilization of the medial meniscus (DMM). In cell experiments, we found that the treatment of geraniol inhibited the expression of IL-1β-induced PGE2, NO, COX-2, iNOS, TNF-α and IL-6 by western blot, qRT-PCR and immunofluorescence staining. Besides, geraniol inhibited the expression of MMP-9 and ADAMTS-5, and reversed the degradation of aggrecan and type II collagen. Mechanistically, we revealed that geraniol suppressed IL-1β-stimulated PI3K/Akt/NF-κB and MAPK activation. Importantly, we have found in animal experiments that oral treatment of geraniol was beneficial in protecting articular cartilage from degradation. Overall, these data indicated that geraniol may have the potential to be developed as an effective treatment for OA.
Insights
Geraniol shows potential for treating osteoarthritis (OA). This study found geraniol reduced inflammation and cartilage degradation in cell and animal models, suggesting it could be an effective OA therapy.
Area of Science:
- Biochemistry
- Pharmacology
- Orthopedics
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease causing significant pain in the elderly.
- Geraniol's therapeutic potential is increasingly recognized, but its efficacy against OA is unestablished.
- Understanding geraniol's effects on cartilage health is crucial for developing new OA treatments.
Purpose of the Study:
- To investigate the anti-inflammatory and anti-cartilage degradation effects of geraniol in osteoarthritis.
- To elucidate the molecular mechanisms underlying geraniol's action in chondrocytes and in vivo OA models.
Main Methods:
- Utilized IL-1β-induced chondrocytes and a destabilization of the medial meniscus (DMM) mouse model.
- Assessed inflammatory markers (PGE2, NO, COX-2, iNOS, TNF-α, IL-6) via Western blot, qRT-PCR, and immunofluorescence.
- Evaluated cartilage degradation markers (MMP-9, ADAMTS-5, aggrecan, type II collagen) and signaling pathways (PI3K/Akt/NF-κB, MAPK).
Main Results:
- Geraniol significantly inhibited IL-1β-induced inflammatory mediators in chondrocytes.
- Geraniol treatment reduced MMP-9 and ADAMTS-5 expression and prevented aggrecan and type II collagen degradation.
- Geraniol suppressed IL-1β-stimulated PI3K/Akt/NF-κB and MAPK signaling pathways.
- Oral administration of geraniol protected articular cartilage from degradation in the DMM mouse model.
Conclusions:
- Geraniol exhibits significant anti-inflammatory and anti-cartilage degradation properties relevant to osteoarthritis.
- The findings suggest geraniol modulates key inflammatory and degradation pathways in OA pathogenesis.
- Geraniol holds promise as a potential therapeutic agent for osteoarthritis treatment.
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