Soh, Li-Jen and Lee, Siam-Yee and Roebuck, Margaret M. and Wong, Pooi-Fong (2024) Unravelling the interplay between ER stress, UPR and the cGAS-STING pathway: Implications for osteoarthritis pathogenesis and treatment strategy. Life Sciences, 357. ISSN 0024-3205, DOI https://doi.org/10.1016/j.lfs.2024.123112.
Full text not available from this repository.Abstract
Osteoarthritis (OA) is a debilitating chronic degenerative disease affecting the whole joint organ leading to pain and disability. Cellular stress and injuries trigger inflammation and the onset of pathophysiological changes ensue after irreparable damage and inability to resolve inflammation, impeding the completion of the healing process. Extracellular matrix (ECM) degradation leads to dysregulated joint tissue metabolism. The reparative effort induces the proliferation of hypertrophic chondrocytes and matrix protein synthesis. Aberrant protein synthesis leads to endoplasmic reticulum (ER) stress and chondrocyte apoptosis with consequent cartilage matrix loss. These events in a vicious cycle perpetuate inflammation, hindering the restoration of normal tissue homeostasis. Recent evidence suggests that inflammatory responses and chondrocyte apoptosis could be caused by the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signalling axis in response to DNA damage. It has been reported that there is a crosstalk between ER stress and cGAS-STING signalling in cellular senescence and other diseases. Based on recent evidence, this review discusses the role of ER stress, Unfolded Protein Response (UPR) and cGAS-STING pathway in mediating inflammatory responses in OA.
| Item Type: | Article |
|---|---|
| Funders: | Fundamental Research Grant Scheme [Grant no. FRGS/1/2022/SKK06/UM/01/2], Ministry of Higher Education, Malaysia [Grant no. FP009-2022] |
| Uncontrolled Keywords: | Endoplasmic reticulum stress; Unfolded protein response; cGAS-STING signalling axis; Inflammation; Osteoarthritis; Treatment strategy |
| Subjects: | R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Medicine > Department of Pharmacology |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 28 Oct 2025 07:47 |
| Last Modified: | 28 Oct 2025 07:47 |
| URI: | http://eprints.um.edu.my/id/eprint/46376 |
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