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19-05-2016 | Osteoarthritis | Review | Article

Ageing and the pathogenesis of osteoarthritis

Journal: Nature Reviews Rheumatology

Authors: Richard F. Loeser, John A. Collins, Brian O. Diekman

Authors: Richard F. Loeser, John A. Collins, Brian O. Diekman

Publisher: Nature Publishing Group UK

Abstract

Ageing-associated changes that affect articular tissues promote the development of osteoarthritis (OA). Although ageing and OA are closely linked, they are independent processes. Several potential mechanisms by which ageing contributes to OA have been elucidated. This Review focuses on the contributions of the following factors: age-related inflammation (also referred to as 'inflammaging'); cellular senescence (including the senescence-associated secretory phenotype (SASP)); mitochondrial dysfunction and oxidative stress; dysfunction in energy metabolism due to reduced activity of 5′-AMP-activated protein kinase (AMPK), which is associated with reduced autophagy; and alterations in cell signalling due to age-related changes in the extracellular matrix. These various processes contribute to the development of OA by promoting a proinflammatory, catabolic state accompanied by increased susceptibility to cell death that together lead to increased joint tissue destruction and defective repair of damaged matrix. The majority of studies to date have focused on articular cartilage, and it will be important to determine whether similar mechanisms occur in other joint tissues. Improved understanding of ageing-related mechanisms that promote OA could lead to the discovery of new targets for therapies that aim to slow or stop the progression of this chronic and disabling condition.

Nat Rev Rheumatol 2016;12:412–420. doi:10.1038/nrrheum.2016.65

Glossary
Telomere attrition
The shortening and deterioration of the protective caps on the ends of chromosomes that is associated with ageing.
Proteostasis
A state of protein homeostasis in which properly folded proteins are stabilized and damaged proteins are degraded.
Cellular senescence
A phenotypic state that can emerge in response to in vitro or in vivo cellular stress. Senescent cells do not divide upon stimulation and often display an altered secretory profile along with increased lysosomal activity.
Stem cell exhaustion
The inability of stem cells to provide a sufficient number of differentiated cells to maintain normal tissue function. Premature stem cell exhaustion can occur under conditions of high demand for progenitors or when aberrant signalling interrupts the maintenance of quiescence.
Senescence-associated secretory phenotype
(SASP). A cellular phenotype that is characterized by the production of high levels of certain inflammatory cytokines and matrix metalloproteinases. The SASP represents a mechanism by which senescent cells may function in a non-autonomous fashion.
Advanced glycation end-products
(AGEs). A diverse set of molecules formed by non-enzymatic reaction of proteins with reducing sugars such as glucose and ribose.
Anabolic dynamic compression
A process by which physical compression of cells within a tissue promotes an anabolic response by the cells.
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