Exosomes are 30–100 nm microvesicles which contain complex cellular signals of RNA, protein and lipids. Because of this, exosomes are implicated as having limitless therapeutic potential for the treatment of cancer, pregnancy complications, infections, and autoimmune diseases. To date we know a considerable amount about exosome biogenesis and secretion, but there is a paucity of data regarding the uptake of exosomes by immune and non-immune cell types (e.g., cancer cells) and the internal signalling pathways by which these exosomes elicit a cellular response. Answering these questions is of paramount importance.
Objective. To explore the involvement of proteaseactivated receptor 1 (PAR-1) and PAR-2 in the pathologic processes of osteoarthritis (OA) and to identify the cells/tissues primarily affected by ablation of PAR-1 or PAR-2 in mice.Methods. OA was induced in the joints of wildtype (WT), PAR-1 ؉/؉ , PAR-1 ؊/؊ , and PAR-2 ؊/؊ mice by destabilization of the medial meniscus (DMM), and scores of histologic features (cartilage aggrecan loss and erosion, subchondral bone sclerosis, osteophytes, and synovitis) were compared at 1, 4, and 8 weeks post-DMM. The effects of PAR ablation on cartilage degradation and chondrocyte metalloproteinase expression/ activity were studied in cultures of mouse femoral head tissue with or without interleukin-1␣ (IL-1␣). At 1 week post-DMM, synovial expression of cytokines and metalloproteinase genes was measured by reverse transcription-polymerase chain reaction, and populations of inflammatory cells were quantified by flow cytometry.Results. Deletion of PAR-2, but not that of PAR-1, in mice significantly delayed the progression of cartilage damage and inhibited subchondral bone sclerosis following DMM. There was no inhibitory effect of PAR-1 or PAR-2 ablation on IL-1␣-induced cartilage degradation or chondrocyte metalloproteinase expression/activation. A low but significant level of synovitis persisted in mice subjected to DMM compared to that in control mice subjected to sham surgery, but no differences between the genotypes were seen 4 or 8 weeks post-DMM. One week after DMM, increased synovial expression of proinflammatory cytokines and metalloproteinase genes, along with increased levels of CD4؉ T cells, inflammatory monocytes, and activated macrophages, were seen in all genotypes. However, there was a significant reduction in the percentage of activated macrophages in PAR-2 ؊/؊ mice compared to PAR-1 ؊/؊ and WT mice.Conclusion. Deletion of PAR-2, but not that of PAR-1, results in a significant decrease in DMMinduced cartilage damage. The chondroprotection in PAR-2 ؊/؊ mice appears to occur indirectly through modulation of extracartilaginous events such as subchondral bone remodeling and synovial macrophage activation, rather than through alteration of chondrocyte catabolic responses.The synovial joint is an "organ" with communication and interdependence between the component tissues and cells necessary for maintenance of normal articular function (1). Osteoarthritis (OA) is the most common arthropathy, and although progressive loss of articular cartilage is pathognomonic, there are varying
Successful pregnancy requires strict temporal regulation of maternal immune function to accommodate the growing fetus. Early implantation is facilitated by inflammatory processes that ensure adequate vascular remodeling and placental invasion. To prevent rejection of the fetus, this inflammation must be curtailed; reproductive immunologists are discovering that this process is orchestrated by the fetal unit and, in particular, the extravillous trophoblast. Soluble and particulate factors produced by the trophoblast regulate maternal immune cells within the decidua, as well as in the periphery. The aim of this review is to discuss the action of recently discovered immunomodulatory factors and mechanisms, and the potential effects of dysregulation of such mechanisms on the maternal immune response that may result in pregnancy loss or preeclampsia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.