Molecular and Cellular Effects of Chemical Chaperone-TUDCA on ER-Stressed NHAC-kn Human Articular Chondrocytes Cultured in Normoxic and Hypoxic Conditions.

Magdalena Kusaczuk,Marzanna Cechowska-Pasko,Monika Naumowicz,Rafał Krętowski,Bartosz Cukierman

doi:10.3390/molecules26040878

Magdalena Kusaczuk, Marzanna Cechowska-Pasko + Show 3 more

Open Access

https://doi.org/10.3390/molecules26040878

Copy DOI

Abstract

Osteoarthritis (OA) is considered one of the most common arthritic diseases characterized by progressive degradation and abnormal remodeling of articular cartilage. Potential therapeutics for OA aim at restoring proper chondrocyte functioning and inhibiting apoptosis. Previous studies have demonstrated that tauroursodeoxycholic acid (TUDCA) showed anti-inflammatory and anti-apoptotic activity in many models of various diseases, acting mainly via alleviation of endoplasmic reticulum (ER) stress. However, little is known about cytoprotective effects of TUDCA on chondrocyte cells. The present study was designed to evaluate potential effects of TUDCA on interleukin-1β (IL-1β) and tunicamycin (TNC)-stimulated NHAC-kn chondrocytes cultured in normoxic and hypoxic conditions. Our results showed that TUDCA alleviated ER stress in TNC-treated chondrocytes, as demonstrated by reduced CHOP expression; however, it was not effective enough to prevent apoptosis of NHAC-kn cells in either normoxia nor hypoxia. However, co-treatment with TUDCA alleviated inflammatory response induced by IL-1β, as shown by down regulation of Il-1β, Il-6, Il-8 and Cox2, and increased the expression of antioxidant enzyme Sod2. Additionally, TUDCA enhanced Col IIα expression in IL-1β- and TNC-stimulated cells, but only in normoxic conditions. Altogether, these results suggest that although TUDCA may display chondoprotective potential in ER-stressed cells, further analyses are still necessary to fully confirm its possible recommendation as potential candidate in OA therapy.

Highlights

Osteoarthritis (OA) is a chronic disease that affects diarthrodial joints
In order to mimic inflammation in cultured chondrocytes, the cells were further treated with 10 ng/mL of IL-1β, which represents an experimental model for inflammation inflammation in vitro [22,40,41,42,43]
Only in normoxic conditions, Tauroursodeoxycholic acid (TUDCA) and hyaluronic acid (HA) were able to signifishowed that in either hypoxia and normoxia, mRNA expression of Il-1β was markedly cantly reduce the expression of Il-1β in comparison to IL-1β only-treated chondrocytes

Summary

Introduction

Osteoarthritis (OA) is a chronic disease that affects diarthrodial joints. This degenerative disorder involves pathology of all joint districts, including synovium, meniscus, bone, ligaments/tendons, and articular cartilage [1]. Multiple risk factors, including obesity, age, prior joint injuries, and genetic factors, contribute to osteoarthritis development, which places OA as a disease with increasing incidence of occurrence in modern societies, but still with limited treatment options [4,5]. One of the joint structures heavily affected by progressing OA is articular cartilage. It is composed of chondrocyte cells, which are the only resident cell type in this structure

Methods

Results

Discussion

Conclusion