# The miR‐6779/XIAP axis alleviates IL‐1β‐induced chondrocyte senescence and extracellular matrix loss in osteoarthritis

## TL;DR

This study shows that miR-6779 reduces chondrocyte aging and cartilage loss in osteoarthritis by targeting the XIAP protein.

## Contribution

The study identifies miR-6779 as a novel regulator of chondrocyte senescence and extracellular matrix degradation in osteoarthritis.

## Key findings

- miR-6779 is significantly down-regulated in osteoarthritis cartilage and IL-1β-treated chondrocytes.
- miR-6779 inhibits XIAP expression, reducing chondrocyte senescence and extracellular matrix loss.
- XIAP overexpression partially reverses the protective effects of miR-6779 on chondrocytes.

## Abstract

Osteoarthritis (OA) is a long‐term degenerative joint disease worsening over time. Aging and chondrocyte senescence contribute to OA progression. MicroRNAs have been confirmed to regulate different cellular processes. They contribute to OA pathology and may help to identify novel biomarkers and therapies for OA.

This study used bioinformatics and experimental investigations to analyze and validate differentially expressed miRNAs in OA that might affect chondrocyte apoptosis and senescence.

miR‐6779 was found to be significantly down‐regulated in OA. Seventy‐six of the predicted and miR‐6779 targeted genes and the OA‐associated disease genes overlapped, and these were enriched in cell proliferation, cell apoptosis, and cell cycle. miR‐6779 overexpression remarkably attenuated IL‐1β effects on chondrocytes by reducing MMP3 and MMP13 levels, promoting cell apoptosis, suppressing cell senescence, and increasing caspase‐3, caspase‐9 and reducing P16 and P21 levels. miR‐6779 targeted inhibition of X‐linked inhibitor of apoptosis protein (XIAP) expression. XIAP knockdown partially improved IL‐1β‐induced chondrocyte senescence and dysfunction. Lastly, when co‐transfected with a miR‐6779 agomir, the XIAP overexpression vector partially attenuated the effects of miR‐6779 overexpression on chondrocytes; miR‐6779 improved IL‐1β‐induced senescence and dysfunction in chondrocytes through targeting XIAP.

miR‐6779 is down‐regulated, and XIAP is up‐regulated in OA cartilage and IL‐1β‐treated chondrocytes. miR‐6779 inhibits XIAP expression, thereby promoting senescent chondrocyte cell apoptosis and reducing chondrocyte senescence and ECM loss through XIAP.

Bioinformatics analysis of the differentially expressed miRNA miR‐6779 in GSE105027 and GSE175961 samples predicted a potential downstream target gene XIAP. Human primary chondrocytes were collected and incubated with interleukin‐1 beta (IL‐1β) to simulate osteoarthritis (OA) in an in vitro environment to establish an OA chondrocyte model. By experimentation, it was found that miR‐6779 was expressed at a higher level in IL‐1β‐induced OA chondrocytes, and that miR‐6779 could target and inhibit XIAP, thereby promoting apoptosis in IL‐1β‐induced OA chondrocytes, inhibiting senescence and the degradation of extracellular matrix.