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Ghrelin protects against osteoarthritis through interplay with Akt and NF-κB signaling pathways
- Publication Year :
- 2018
- Publisher :
- US : Federation of American Societies for Experimental Biology, 2018.
-
Abstract
- Osteoarthritis (OA) is a common chronic degenerative disease characterized by degeneration in the joints and subsequent destruction of cartilage and bone, yet much remains to be elucidated regarding its molecular mechanism. Ghrelin is a recently discovered neuropeptide with anti-inflammatory actions, but it is unknown whether ghrelin is involved in OA. Human primary chondrocyte and cartilage samples were collected from patients with OA, and the expression pattern of ghrelin was assessed. Human chondrocyte and cartilage samples were stimulated with IL-1β and TNF-α, and exogenous ghrelin-alleviated disorganization of catabolism and anabolism were mediated by IL-1β and TNF-α. Destabilization of the medial meniscus and anterior cruciate ligament transection models were established in wild-type mice that were administered ghrelin or PBS. Severity of inflammation and degeneration in the joints were determined by measuring the levels of various inflammatory cytokines and degeneration-associated molecules. Ghrelin down-regulated the production of various inflammatory cytokines, inhibited apoptosis of chondrocytes, decreased the levels of metalloproteinases (including matrix metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motif-5), and maintained the expression of critical matrix components, such as aggrecan and collagen 2. Moreover, suppression of the Akt signaling pathway and activation of NF-κB signaling in chondrocytes during OA development was antagonized by ghrelin administration. This supports the assessment of ghrelin as a potential therapeutic approach to treat degenerative cartilage diseases, including OA.-Qu, R., Chen, X., Wang, W., Qiu, C., Ban, M., Guo, L., Vasilev, K., Chen, J., Li, W., Zhao, Y. Ghrelin protects against osteoarthritis through interplay with Akt and NF-κB signaling pathways.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
inflammatory cytokines
Interleukin-1beta
Biochemistry
Chondrocyte
Proinflammatory cytokine
Mice
03 medical and health sciences
Chondrocytes
Internal medicine
Matrix Metalloproteinase 13
Osteoarthritis
Genetics
medicine
Animals
cartilage
Molecular Biology
Protein kinase B
Aggrecan
Tumor Necrosis Factor-alpha
Akt/PKB signaling pathway
business.industry
Cartilage
digestive, oral, and skin physiology
NF-kappa B
Ghrelin
030104 developmental biology
medicine.anatomical_structure
Endocrinology
IL-1β
TNF-α
chondrocyte
Signal transduction
business
Proto-Oncogene Proteins c-akt
Signal Transduction
Biotechnology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....3558b890fa83298eccecf170380db60d