Lovastatin impairs cellular proliferation and enhances hyaluronic acid production in fibroblast-like synoviocytes.

INTRODUCTION: Statins have demonstrated chondroprotective effects by reducing inflammation and mitigating extracellular matrix degradation. However, statins are also reported to be cytotoxic to several types of cells. Early-onset osteoarthritis (OA) is characterized by synovial inflammation, which adversely affects hyaluronan (HA) production in fibroblast-like synoviocytes (FLSs). Nevertheless, the precise effects of statins on the synovium remain unclear. METHODS: This study investigated the impact of lovastatin on human FLSs, and HA secretion-related genes, signaling pathways, and production were evaluated. RESULTS: The findings revealed that high doses of lovastatin (20 or 40 µM) decreased FLS viability and increased cell death. FLS proliferation ceased when cultured in a medium containing 5 or 10 µM lovastatin. mRNA expression analysis demonstrated that lovastatin (5 and 10 µM) upregulated the gene level of hyaluronan synthase 1 (HAS1), HAS2, and proteoglycan 4 (PRG4), but not HAS3. While the expression of multidrug resistance-associated protein 5 transporter gene remained unaffected, both inward-rectifying potassium channel and acid-sensing ion channel 3 were upregulated. Western blot further confirmed that lovastatin increased the production of HAS1 and PRG4, and activated the PKC-α, ERK1/2, and p38-MAPK signaling pathways. Additionally, lovastatin elevated intracellular cAMP levels and HA production in FLSs. CONCLUSION: Lovastatin impairs cellular proliferation but enhances HA production in human FLSs.

Conjunctive Analysis of BSA-Seq and SSR Markers Unveil the Candidate Genes for Resistance to Rice False Smut.

Rice false smut (RFS) caused by the fungus Ustilaginoidea virens (Cook) leads to serious yield losses in rice. Identification of the gene or quantitative trait loci (QTLs) is crucial to resistance breeding and mitigation of RFS damage. In this study, we crossed a resistant variety, IR77298-14-1-2::IRGC117374-1, with a susceptible indica cultivar, 9311, and evaluated recombinant inbred lines in a greenhouse. The genetic analysis showed that the RFS resistance of IR77298-14-1-2::IRGC117374-1 was controlled by multiple recessive loci. We identified a novel QTL, qRFS12.01, for RFS resistance in IR77298-14-1-2::IRGC117374-1 by combining bulked segregant analysis with whole genome resequencing (BSA-seq) and simple sequence repeat (SSR) marker mapping approaches. The phenotypic effect of qRFS12.01 on RFS resistance reached 28.74%, suggesting that SSR markers linked to qRFS12.01 are valuable for marker-assisted breeding of RFS resistance in rice. The prediction of putative candidate genes within qRFS12.01 revealed five disease resistance proteins containing NB-ARC domains. In conclusion, our findings provide a new rice chromosome region carrying genes/QTLs for resistance to RFS.