Osteoarthritis: aging of matrix and cells--going for a remedy.

It has been known for a very long time that aging is the most prominent risk factor for the initiation and progression of osteoarthritis. This might be related to continuous mechanical wear and tear and/or result from time/age-related modifications of cartilage matrix components. Also a mere loss of viable cells over time, due to apoptosis or any other mechanism, might contribute. More recent evidence, however, supports that stressful conditions for the cells might promote chondrocyte senescence and might be in particular important for the progression of the osteoarthritic disease process. One of the most important implications of this hypothesis is that it points to issues of cellular degeneration as the basis for understanding of the initiation and the progression of osteoarthritis. Equally important, it emphasizes that whatever treatment we envisage for osteoarthritis, we must take into account that we are dealing with aged/(pre)senescent cells which no longer have the abilities of their juvenile counterparts to respond to the many mechanical, inflammatory, and traumatic assaults to the tissue. Thirdly, this directs treatment options to deal with the senescence of cells, which are only conceptually available today. Clearly, if accumulation of wear and tear over time is the major scenario of osteoarthritis, any therapy will largely be hopeless as moving and loading the joints is unavoidable as implication of their use. However, this review intends to open up the idea that age-related changes are less a fate, but rather a challenge for therapeutic intervention which can be taken.