Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Autophagy Is a Protective Mechanism in Normal Cartilage and Its Aging-Related Loss Is Linked with Cell Death and Osteoarthritis

Carames1,  Beatriz, Taniguchi1,  Noboru, Otsuki1,  Shuhei, Blanco2,  Francisco J., Lotz1,  Martin K.

The Scripps Research Institute, La Jolla, CA
INIBIC–Complejo Hospitalario Universitario A Coruña, A Coruña, Spain

Purpose:

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.

Method:

DNA array studies were performed to analyze differences in the expression of ULK1 in normal and OA human knee cartilage. Protein expression of ULK1, Beclin1 and LC3 was analyzed in human normal and OA chondrocytes and cartilage by western blot and immunohistochemistry (IHC). Autophagy markers were also studied in mouse models of aging-associated and surgically-induced OA. The apoptosis marker poly-ADP(ribose) polymerase (Parp p85) was used to determine the relationship between cell death and autophagy.

Results:

In normal human articular cartilage ULK1, Beclin1 and LC3 were constitutively expressed. ULK1 gene expression and ULK1, Beclin1 and LC3 protein expression were reduced in OA chondrocytes and cartilage but these three proteins were expressed in the cell clusters in OA cartilage. In mouse knee joints loss of glycosaminoglycans (GAGs) was observed at 9 months of age and in the surgical OA model 8 weeks after knee destabilization. Expression of ULK1, Beclin1 and LC3 decreased together with loss of GAGs, suggesting decreased autophagy correlates with extracellular matrix changes in OA. The decrease in autophagy in the same human and mouse OA cartilage was associated with an increase in Parp p85.

Conclusion:

Autophagy may be a protective or homeostatic mechanism in normal cartilage. By contrast, human OA, spontaneous 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.

To cite this abstract, please use the following information:
Carames, Beatriz, Taniguchi, Noboru, Otsuki, Shuhei, Blanco, Francisco J., Lotz, Martin K.; Autophagy Is a Protective Mechanism in Normal Cartilage and Its Aging-Related Loss Is Linked with Cell Death and Osteoarthritis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1298
DOI: 10.1002/art.26372

Abstract Supplement

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