Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 449, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2022.116135
Keywords
Osteoarthritis; Polychlorinated biphenyl 153; microRNA-155; RICTOR; Chondrocyte; PI3K/Akt/mTOR signaling
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Funding
- Educational Department of Liaoning Province [LJKZ0747]
- Key R&D Program of Liaoning Province [2020JH2/10300144]
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This study found that PCB153 is associated with the occurrence and development of osteoarthritis (OA) by activating the PI3K/Akt/mTOR and RICTOR/Akt/mTOR signaling pathways, suppressing autophagy, and promoting the degradation of the extracellular matrix of chondrocytes.
Polychlorinated biphenyls (PCBs) are a typical type of persistent organic pollutant. PCB exposure is associated to the occurrence and development of osteoarthritis (OA); however, the involved mechanisms have yet to be elucidated. Here, we investigated the pro-osteoarthritic effect of 2, 2 ', 4, 4 ', 5, 5 '-hexachlorobiphenyl (PCB153), and the involvement of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) and the RICTOR/Akt/mTOR signaling pathways. PCB153 of 20 and 30 mu M increased the expression of MMP13 and decreased the expression of type II collagen, in a concentration-dependent manner. PCB153 treatment reduced the expression of Beclin 1 and LC3B, but increased the expression of p62 by upregulating miR-155 levels. PCB153 treatment activated the PI3K/Akt/mTOR signaling pathway by upregulating miR-155 levels. RICTOR was involved in activating the Akt/mTOR signaling pathway, and was also regulated by miR-155. In conclusion, PCB153 could promote the degradation of the extracellular matrix of chondrocytes by upregulating miR-155 via a mechanism related to the activation of the PI3K/Akt/mTOR and RICTOR/Akt/mTOR signaling pathway, which suppressed autophagy and facilitated the development of OA. MiR-155 may represent potential therapeutic targets to alleviate the development of OA.
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