Osteoarthritis is a common age-related degenerative joint condition in which cartilage and bone are lost, though in the earlier stages of the condition, changes in cartilage are more subtle and complicated in their effects. While not traditionally seen as an inflammatory condition, as there is no evident, visible joint inflammation as occurs in other forms of arthritis, there is nonetheless a strong case for considering osteoarthritis to be driven by localized inflammation. Recently, the increased number of senescent cells in aged joint tissue has been shown to contribute directly to the development of osteoarthritis. Indeed, osteoarthritis will be near the top of the list of conditions that Unity Biotechnology plans to treat with senolytic drugs capable of selectively destroy senescent cells. These unwanted cells generate inflammation through the signaling molecules they create, and thus a role in osteoarthritis makes a lot of sense in hindsight.
Today’s open access paper on the relationship between age and osteoarthritis focuses more on oxidative stress than on inflammation, however. Oxidative stress is the excessive generation of oxidative molecules by cells, which can cause damage or even cell death, but perhaps just as importantly it can alter cellular behavior in quite sweeping ways. Oxidative stress and inflammation often go hand in hand, and there is plenty of evidence to suggest that one is capable of causing the other, with the arrow of causation pointing in either direction. So one might take this paper as a different view of the same overall set of mechanisms, a different emphasis on investigation and intervention.
Nonetheless, if you read through the observations, it is clear that a sizable number of those thought most relevant to the development of osteoarthritis point towards the activities of senescent cells in one way or another. This perhaps even includes the oxidative stress given the lines that can be drawn between cellular senescence and mitochondrial dysfunction, and between inflammation and oxidative stress, though clearly the age-related cross-linking found in cartilage has its own independent and significantly detrimental effects. This isn’t just senescent cells at work, even if it turns out to be mostly senescent cells at work. Fortunately the advent of senolytics will enable researchers to make inroads into disentangling these various causes and their consequences: removing one of the causes is the fastest and most effective way to determine the size of its contribution and its relationship with other mechanisms.