# CircCDK14 protects against Osteoarthritis by sponging miR-125a-5p and promoting the expression of Smad2

## TL;DR

This study shows that CircCDK14 helps protect cartilage in osteoarthritis by interacting with miR-125a-5p and Smad2, offering a new potential treatment approach.

## Contribution

The study identifies CircCDK14 as a novel circRNA that protects against osteoarthritis by sponging miR-125a-5p and modulating Smad2 expression.

## Key findings

- CircCDK14 is downregulated in osteoarthritis and protects cartilage by inhibiting apoptosis and promoting proliferation.
- CircCDK14 sponges miR-125a-5p, leading to reduced Smad2 expression and impaired TGF-β signaling.
- Intra-articular delivery of CircCDK14 in rabbits alleviated osteoarthritis symptoms.

## Abstract

Rationale: Osteoarthritis (OA) is the most common joint disease worldwide. Previous studies have identified the imbalance between extracellular matrix (ECM) catabolism and anabolism in cartilage tissue as the main cause. To date, there is no cure for OA despite a few symptomatic treatments. This study aimed to investigate the role of CircCDK14, a novel circRNA factor, in the progression of OA, and to elucidate its underlying molecular mechanisms.

Methods: The function of CircCDK14 in OA, as well as the interaction between CircCDK14 and its downstream target (miR-125a-5p) and mRNA target (Smad2), was evaluated by western blot (WB), immunofluorescence (IF), RNA immunoprecipitation (RIP), quantitative RT-PCR, luciferase assay and fluorescence in situ hybridization (FISH). Rabbit models were introduced to examine the function and mechanism of CircCDK14 in OA in vivo.

Results: In our present study, we found that CircCDK14, while being down-regulated in the joint wearing position, regulated metabolism, inhibited apoptosis and promoted proliferation in the cartilage. Mechanically, the protective effect of CircCDK14 was mediated by miR-125a-5p sponging, which downregulated the Smad2 expression and led to the dysfunction of TGF-β signaling pathway. Intra-articular injection of adeno-associated virus-CircCDK14 also alleviated OA in the rabbit model.

Conclusion: Our study revealed an important role of CircCDK14/miR-125a-5p/Smad2 axis in OA progression and provided a potential molecular therapeutic strategy for the treatment of OA.