Autophagy is a Protective Mechanism in Normal Cartilage and its Aging-related Loss is Linked with Cell Death and Osteoarthritis

By B. Caramés, N. Taniguchi, S. Otsuki, F. Blanco, M. Lotz. Arthritis & Rheumatism, 2010

627 citations recorded by the source corpus.

Objective Autophagy is a process for turnover of intracellular organelles and molecules that protects cells during stress responses. This study evaluated the potential role of ULK1, an inducer of autophagy, Beclin1, a regulator of autophagy and LC3, which executes autophagy, in the development of osteoarthritis (OA) and in cartilage cell death. Methods Expression of ULK1, Beclin1 and LC3 were analyzed in normal and OA human articular cartilage and in knee joints of mice with aging-related and surgically induced OA by using immunohistochemistry (IHC) and western blotting. Poly-ADP(ribose) polymerase (Parp p85) was used to determine the correlation between cell death and autophagy. Results In normal human articular cartilage ULK1, Beclin1 and LC3 were constitutively expressed. ULK1, Beclin1 and LC3 protein expression were reduced in OA chondrocytes and cartilage but these three proteins were strongly expressed in the OA cell clusters. In mouse knee joints loss of glycosaminoglycans (GAGs) was observed at 9 and 12 months of age and in the surgical OA model 8 weeks after knee destabilization. Expression of ULK1, Beclin1 and LC3 decreased together with GAG loss while Parp p85 was increased. Conclusion Autophagy may be a protective or homeostatic mechanism in normal cartilage. By contrast, human OA, aging-related and surgically-induced OA in mice are associated with a reduction and loss of ULK1, Beclin1 and LC3 expression and a related increase in apoptosis. These results suggest that compromised autophagy represents a novel mechanism in the development of OA.

Subfields: Cancer Research, Epidemiology, Rheumatology

View Paper: https://www.semanticscholar.org/paper/d610d2ce355aeb7f55b1be4420bd97d3195ba9d5

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In Cancer Research

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Citations in the corpus

• Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis (2015, background): “In addition, pro-inflammatory cytokines provoke inflammatory responses and inhibit autophagy, leading to an increase in chondrocyte apoptosis [88].”
• Inflammation in osteoarthritis (2011, background): “The agingrelated loss of autophagy, a protective mechanism for normal chondrocytes that protects cells during stress responses, is associated with cell death and osteoarthritis development [47].”
• Osteoarthritis: a disease of the joint as an organ. (2012, background): “Increased production of ROS mediated by mechanical injury or in response to cytokines and matrix fragments may also contribute to cell death (37) as well as a decline in autophagy which serves as a protective mechanism used by cells under stress (38).”