Work

Intrinsic amyloid deposition following proteostasis impairment in osteoarthritic chondrocytes: Insights and therapeutic approaches

Year: 2025

Type: article

Abstract: Osteoarthritis (OA) is the most common age-related and degenerative joint disease. Proteostasis and protein quality control (autophagy, unfolded protein response, and the ubiquitin-proteasome system) are pivotal for cellular homeostasis and their impairment leads to protein misfolding and amyloid deposition in aged tissues. We here investigated amyloid deposition in OA. Amyloid fibrils were observed in chondrocytes in ex vivo cartilage samples. The underlying mechanisms were assessed in vitro: chondrocytes and cartilage organ cultures were treated with chloroquine and/or lipopolysaccharide for assessment (Western Blotting, immunohistochemistry, histochemistry cytofluorimetry) of amyloid deposition after induction of ER stress with/without blockage of autophagy. Overall, our data show for the first time that proteostasis impairment leads to intrinsic amyloid deposition in OA chondrocytes. These effects were mitigated by selected polyphenols. In conclusion, amyloidosis could contribute to OA progression, and the failure of proteostasis, a hallmark of aging, represents a promising therapeutic target.

Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

DOI: 10.1016/j.bbadis.2025.167865