Joint aging and chondrocyte cell death

Abstract

Articular cartilage extracellular matrix and cell function change with age and are considered to be the most important factors in the development and progression of osteoarthritis. The multifaceted nature of joint disease indicates that the contribution of cell death can be an important factor at early and late stages of osteoarthritis. Therefore, the pharmacologic inhibition of cell death is likely to be clinically valuable at any stage of the disease. In this article, we will discuss the close association between diverse changes in cartilage aging, how altered conditions influence chondrocyte death, and the implications of preventing cell loss to retard osteoarthritis progression and preserve tissue homeostasis.

Figures

Figure 1. Cellular and extracellular matrix changes associated with age that lead to chondrocyte death and osteoarthritis development in articular cartilage

Cell density reduces with age and ECM properties are altered with age, resulting in reduced load-bearing capacity. All of these changes increase the tissue’s vulnerability to loading/injury cell death (necrotic and apoptotic). Continued loading on compromised tissue leads to further cell death and matrix degradation. ECM: Extracellular matrix; MMP: Matrix metalloproteinase.

Figure 2. Cellular and extracellular matrix changes associated with age that lead to chondrocyte death and osteoarthritis development in articular cartilage

Summary of cell-based (intrinsic and extrinsic) factors known to change with age and alter cell viability (see text for details). ECM: Extracellular matrix; MMP: Matrix metalloproteinase; RAGE: Receptor for advanced glycation end products; ROS: Reactive oxygen species.