Histological Evaluation and Gene Expression Profiling of Autophagy-Related Genes for Cartilage of Young and Senescent Rats

Abstract

Autophagy is a cellular mechanism that protects cells from stress by digesting non-functional cellular components. In the cartilage, chondrocytes depend on autophagy as a principal mechanism to maintain cellular homeostasis. This protective role diminishes prior to the structural damage that normally occurs during aging. Considering that aging is the main risk factor for osteoarthritis, evaluating the expression of genes associated with autophagy in senescent cartilage might allow for the identification of potential therapeutic targets for treatment. Thus, we studied two groups of young and senescent rats. A histological analysis of cartilage and gene expression quantification for autophagy-related genes were performed. In aged cartilage, morphological changes were observed, such as an increase in cartilage degeneration as measured by the modified Mankin score, a decrease in the number of chondrocytes and collagen II (Col2a1), and an increase in matrix metalloproteinase 13 (Mmp13). Moreover, 84 genes associated with autophagy were evaluated by a PCR array analysis, and 15 of them were found to be significantly decreased with aging. Furthermore, an in silico analysis based on by two different bioinformatics software tools revealed that several processes including cellular homeostasis, autophagosome assembly, and aging—as well as several biological pathways such as autophagy, insulin-like growth factor 1 (IGF-1) signaling, PI3K (phosphoinositide 3-kinase)/AKT (serine/threonine kinase) signaling, and mammalian target of rapamycin (mTOR) signaling—were enriched. In conclusion, the analysis identified some potential targets for osteoarthritis treatment that would allow for the development of new therapeutic strategies for this chronic disease.

Geographic Area of Collection Determines the Chemical Composition and Antimicrobial Potential of Three Extracts of Chilean Propolis

“…Chilean propolis exhibited antibiofilm potential and antimicrobial activities when it was evaluated on Streptococcus mutans cultures [ 28 , 29 ]. The antimicrobial activities of propolis with aromatic acids (ferulic, cinnamic, caffeic and p-coumaric acids) was described as having strong antibacterial actions against Gram-positive and Gram-negative bacteria [ 30 ].In addition, polyphenols from propolis showed anti-inflammatory activity, could act in the synthesis of matrix metalloproteinases and were identified as a potential target for osteoarthritis treatment and for reducing nociceptive pain in animal models [ 31 , 32 , 33 ].…”

Ethanolic Extract of Propolis Modulates Autophagy-Related microRNAs in Osteoarthritic Chondrocytes

“…It had already been described that in cartilage, several proteins associated with the autophagy pathway are deregulated by aging [50]. Specifically, among the deregulated genes associated with aging in cartilage, three proteins-AKT1, ATG5, and LC3A-were selected due to their common use as markers for autophagy [17].…”

Autophagy targeting nanoparticles in rheumatoid arthritis and osteoarthritis

“…21 The intense effect of autophagy was found in the rat OA model in the superficial layer of bones and intermediate zones of articular cartilage. 22 During OA, the death of chondrocytes and associated extracellular matrix loss are the main causing factors behind articular degeneration; however, the mechanism of death is not known clearly so far. This series of findings suggested the possible role of both apoptotic and non-apoptotic signals.…”