Skip to main page content
U.S. flag
See More

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017:128:44-54.

The Role of Aging in the Development of Osteoarthritis

Richard F Loeser  1
Affiliations
Review

The Role of Aging in the Development of Osteoarthritis

Richard F Loeser. Trans Am Clin Climatol Assoc. 2017.

Abstract

Osteoarthritis (OA) is the most common form of arthritis and a significant cause of pain and disability in older adults. Among the risk factors for OA, age is the most prominent. This review will discuss the relationship between aging and the development of OA, with a particular focus on mechanisms relevant to cartilage degeneration and the role of excessive levels of reactive oxygen species. Rather than just causing random oxidative damage, an increase in reactive oxygen species that leads to oxidative stress disrupts specific cell signaling pathways. This disruption in cell signaling affects the ability to maintain the cartilage extracellular matrix and eventually causes cell death. By understanding the specific cell signaling pathways that lead to OA through altered redox signaling, novel targets will be discovered that will be an advance over the current non-targeted anti-oxidant approach that has not been successful in treating chronic diseases of aging such as OA.

PubMed Disclaimer

Conflict of interest statement

Potential Conflicts of Interest: This work was supported by grants from the National Institute on Aging (RO1 AG044034) and the National Institute of Arthritis, Musculoskeletal, and Skin Disease (R37 AR049003). Dr. Loeser serves as a consultant for Unity Biotechnology.

Figures

Fig. 1
Fig. 1
Oxidative stress due to aging contributes to the development of osteoarthritis. Age-related oxidative stress results in increased levels of reactive oxygen species (ROS) in articular chondrocytes. Excessive ROS disrupts cell signaling to inhibit anabolic and promote catabolic signaling that results in reduced matrix production and increased production of matrix metalloproteinases (MMPs) and pro-inflammatory cytokines as well as increased chondrocyte death. These changes in turn lead to cartilage destruction and osteoarthritis.
Fig. 2
Fig. 2
Mechanism by which increased levels reactive oxygen species (ROS) disrupt signaling through hyperoxidation of peroxiredoxins. Low physiologic levels of ROS are controlled by the peroxiredoxins (Prxs) and promote phosphoinositide 3 (PI-3) kinase-Akt signaling. As levels of ROS rise, Prxs are hyperoxidized to the PrxSO2/3 state which causing their inactivation and loss of redox control. This results in the inhibition of PI-3 kinase-Akt signaling and activation of specific mitogen-activated protein (MAP) kinase signaling pathways that increase production of matrix degrading enzymes and eventually cause cell death resulting in cartilage destruction and osteoarthritis.
See this image and copyright information in PMC

References

    1. Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation–united states, 2003–2005. MMWR Morb Mortal Wkly Rep. 2006;55:1089–92. - PubMed
    1. Cisternas MG, Murphy L, Sacks JJ, et al. Alternative methods for defining osteoarthritis and the impact on estimating prevalence in a us population-based survey. Arthritis Care Res. 2016;68:574–80. - PMC - PubMed
    1. Hootman JM, Helmick CG. Projections of us prevalence of arthritis and associated activity limitations. Arthritis Rheum. 2006;54:226–9. - PubMed
    1. Losina E, Paltiel AD, Weinstein AM, et al. Lifetime medical costs of knee osteoarthritis management in the united states: impact of extending indications for total knee arthroplasty. Arthritis Care Res. 2015;67:203–15. - PMC - PubMed
    1. Hunter DJ, Beavers DP, Eckstein F, et al. The intensive diet and exercise for arthritis (idea) trial: 18-month radiographic and mri outcomes. Osteoarthritis Cartilage. 2015;23:1090–8. - PMC - PubMed

Substances

LinkOut - more resources