Affiliation:
1. Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology Southern Medical University Guangzhou China
Abstract
AbstractRecent studies have shed light on the important role of aging in the pathogenesis of joint degenerative diseases and the anti‐aging effect of alpha‐ketoglutarate (αKG). However, whether αKG has any effect on temporomandibular joint osteoarthritis (TMJOA) is unknown. Here, we demonstrate that αKG administration improves condylar cartilage health of middle‐aged/aged mice, and ameliorates pathological changes in a rat model of partial discectomy (PDE) induced TMJOA. In vitro, αKG reverses IL‐1β‐induced/H2O2‐induced decrease of chondrogenic markers (Col2, Acan and Sox9), and inhibited IL‐1β‐induced/ H2O2‐induced elevation of cartilage catabolic markers (ADAMTS5 and MMP13) in condylar chondrocytes. In addition, αKG downregulates senescence‐associated (SA) hallmarks of aged chondrocytes, including the mRNA/protein level of SA genes (p16 and p53), markers of nuclear disorders (Lamin A/C) and SA‐β‐gal activities. Mechanically, αKG decreases the expressions of p‐IKK and p‐NF‐κB, protecting TMJ from inflammation and senescence‐related damage by regulating the NF‐κB signaling. Collectively, our findings illuminate that αKG can ameliorate age‐related TMJOA and PDE‐induced TMJOA, maintain the homeostasis of cartilage matrix, and exert anti‐aging effects in chondrocytes, with a promising therapeutic potential in TMJOA, especially age‐related TMJOA.
Funder
Basic and Applied Basic Research Foundation of Guangdong Province
Cited by
1 articles.
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