Adipose-Derived Stem Cells Suppress Inflammation Induced by IL-1β through Down-Regulation of P2X7R Mediated by miR-373 in Chondrocytes of Osteoarthritis

Abstract

Adipose-derived stem cells (ADSCs) were previously considered to have an anti-inflammatory effect, and Interleukin-1β (IL-1β) was found to be a pro-inflammatory factor in chondrocytes, but the mechanism underlying ADSCs and IL-1β is unclear. In this study, we investigate whether P2X7 receptor (P2X7R) signalling, regulated by microRNA 373 (miR-373), was involved in the ADSCs and IL-1β mediated inflammation in osteoarthritis (OA). Chondrocytes were collected from 20 OA patients and 20 control participants, and ADSCs were collected from patients who had undergone abdominal surgery. The typical surface molecules of ASDCs were detected by flow cytometry. The level of nitric oxide (NO) was determined by Griess reagent. Concentrations of prostaglandin E2 (PGE2), interleukin 6 (IL-6), matrix metallopeptidase 3 (MMP-3) were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of IL-6, MMP-3, miR-373 and P2X7R were determined by real-time polymerase chain reaction (PCR), and Western blot was used to detect the protein expression of P2X7R. The typical potential characters of ADSCs were verified. In chondrocytes or OA tissues, the miR-373 expression level was decreased, but the P2X7R expression was increased. IL-1β stimulation increased the level of inflammatory factors in OA chondrocytes, and ADSCs co-cultured with IL-1β-stimulated chondrocytes decreased the inflammation. OA chondrocytes transfected with the miR-373 inhibitor increased the inflammation level. The miR-373 mimic suppressed the inflammation by targeting P2X7R and regulated its expression, while its effect was reversed by overexpression of P2X7R. IL-1β induced inflammation in OA chondrocytes, while ADSCs seemed to inhibit the expression of P2X7R that was regulated by miR-373 and involved in the anti-inflammatory process in OA.

Adipose-derived mesenchymal stem cells protect against CMS-induced depression-like behaviors in mice via regulating the Nrf2/HO-1 and TLR4/NF-κB signaling pathways

“…ADSCs were isolated as previously described [ 24 ]. Briefly, adipose tissue from mouse abdominal fat pads was isolated and washed with phosphate-buffered saline (PBS) and minced before digestion with 0.2% collagenase I (Sigma-Aldrich, St. Louis, MO, USA) for 1 h at 37 °C with intermittent shaking.…”

“…After transplantation, ADSCs can engraft in brain tissue and differentiate in situ into neurons and glial cells, and as a result, ADSCs are usually used in peripheral nerve regeneration [ 20 – 22 ]. Recently, studies have found that ADSC transplantation therapy has anti-inflammatory effects [ 23 , 24 ]. In the present study, we studied the therapeutic mechanism of ADSCs in depression and sought to elucidate the relationship between Nrf2 and microglial phenotype by using a chronic mild stress (CMS)-induced depressive mouse model and lipopolysaccharide (LPS)-induced inflammatory cell model.…”

<p>Epigallocatechin-3-gallate enhances the osteoblastogenic differentiation of human adipose-derived stem cells</p>

“…In all experiments, hASCs at passage 4 were used. The phenotype profile of hASCs (passage 4) was evaluated through flow cytometry analysis using PE-labeled cluster designation CD29, CD31, CD44, CD45, CD73, CD90, and CD105 antibodies (data not shown) 31,32…”

Can mesenchymal stem cells and their conditioned medium assist inflammatory chondrocytes recovery?

“…They found all three different kinds of AD-MSC (from infrapatellar Hoffa fat, subcutaneous hip fat and subcutaneous abdominal fat) could reduce the expression of IL-1β, IL-6, and CXCL8/IL-8 level on chondrocyte. Rilong Jin’s group also found human AD-MSC could down-regulate the amount of NO, PGE-2 and MMP-3, and decrease IL-6 gene expression of chondrocyte pre-treated with IL-1β [ 29 ]. Li et al found AD-MSCs could down-upregulation of MMP-3, MMP-13, TNF-α and IL-6 in chondrocytes [ 30 ].…”