Anti‐inflammatory effects of hydrophilic and lipophilic statins with hyaluronic acid against LPS‐induced inflammation in porcine articular chondrocytes

Abstract

The objective of the study is to understand the therapeutic effects of lipophilic (simvastatin) and hydrophilic statins (pravastatin) combined with/without hyaluronic acid for osteoarthritis by an in vitro LPS-induced inflammatory model of articular chondrocytes. HA in combination with different doses of simvastatin or pravastatin were used. Beside cytotoxicity, the influence of statins on NO production, pro-inflammatory cytokine, inflammatory mediators, and NF-kB p50 protein were analyzed. Finally, TUNEL assay was performed to detect DNA strand breakage. Two statins were less able to lower NF-kB activity when they were administrated along without HA. The gene expression demonstrates that simvastatin and pravastatin had the ability to decrease pro-inflammatory and inflammatory mediator levels. High dose simvastatin with or without HA down regulated inflammatory cytokines, but resulted in higher cytotoxicity. TUNEL assay confirms the regulatory effect of statins with or without HA over the apoptosis of chondrocytes, especially in hydrophilic statins. The significant down-regulation of inflammatory mediators suggests that intra-articular injection of HA in combination with statins might feasibly slow the progress of osteoarthritis. Administration of simvastatin or pravastatin with hyaluronic acid may produce beneficial effects for OA treatment, but with better results when hydrophilic statin was used. ß

Guiding synovial inflammation by macrophage phenotype modulation: an in vitro study towards a therapy for osteoarthritis

“…Although statins are known for their pleiotropic effects, pravastatin did not have a clear modulatory effect on OA synovial tissue in our study. On polarized macrophages however, pravastatin increased sCD163 production in both anti-inflammatory phenotypes, which is in line with other studies that have shown antiinflammatory effects of statins on macrophage polarization 42,43 , chondrocytes 44,45 , and progression of OA and arthritis in vivo 46,47 . Additionally, systemic statin use has also been shown to be associated with reduced progression of knee OA 48 and seemed to reduce the activity of rheumatoid arthritis in humans 49 .…”

Retracted: Long noncoding RNA MALAT1 alleviates lipopolysaccharide‐induced inflammatory injury by upregulating microRNA‐19b in murine chondrogenic ATDC5 cells

“…25 LPS could activate inflammatory response in vitro and in vivo by enhancing the expressions of proinflammatory cytokines, F I G U R E 5 MALAT1 alleviated LPS-induced ATDC5 cell inflammatory injury by upregulating miR-19b. 27,28 In this study, LPS treatment dramatically inhibited murine chondrogenic ATDC5 cell viability, induced ATDC5 cell apoptosis, and enhanced proinflammatory cytokines expression. B-D, After 5 μg/mL LPS treatment and/or pEX-MALAT1 (miR-19b inhibitor) transfection, the viability of ATDC5 cells, apoptosis of ATDC5 cells, and expression levels of Bcl-2, Bax, pro-caspase 3, cleaved-caspase 3, pro-caspase 9, and cleaved-caspase 9 in ATDC5 cells were measured using CCK-8 assay, annexin V-PE staining, and Western blot analysis, respectively.…”

Effects of tetrahedral framework nucleic acid/wogonin complexes on osteoarthritis

“…Due to the high levels of pro-inflammatory cytokines and the many dead chondrocytes in OA joints, recent research of OA treatment has focused on exploring agents that can inhibit chondrocyte apoptosis, promote chondrocyte proliferation, and reduce the levels of catabolic factors involved in OA to slow or reverse OA progression. [17][18][19][20] In terms of chondroprotective effect, we found that tetrahedral framework nucleic acid (TFNA), a specific, novel, and very promising DNA nanomaterial, can maintain the morphology of chondrocytes and enhance chondrocyte proliferation by activating the Notch signaling pathway and promote the migration of chondrocytes by activating the RhoA/ROCK signaling pathway at an optimum concentration of 250 nmol·L −1 . [21][22][23] TFNA can also be easily synthesized using several unique methods and specifically designed single-stranded DNA (ssDNA) by utilizing unique and sophisticated Watson-Crick base pairing.…”