Obesity, Osteoarthritis and Aging: The Biomechanical Links - The Mechanobiology of Obesity and Related Diseases - page 187

Antioxidant
Capacity?

Pathologic Physiologic Pathologic

Biomechanical Loading

Fig. 5 Theoretical model of the effect of biomechanical loading on ROS production and the
development of cartilage redox stress, defined as the disruption of redox signaling and control
and/or molecular damage. Physiologic loading is expected to improve redox homeostasis by
increasing antioxidant capacity via ROS-dependent feedback mechanisms. Insufficient ROS
production due to an absence of loading and/or hyperphysiologic ROS production due to
traumatic loading are both risk factors for redox stress. Obesity may increase cartilage redox
stress due to a combination of pathologic physical inactivity and pathologic joint loading

antioxidant capacity, thereby providing an adaptive response to protect against
joint inflammation and cellular oxidative stress. Because obesity is associated with
a reduction in cyclic joint loading due to low levels of daily physical activity,
chondrocytes in weight-bearing joints from obese individuals may be more sus-
ceptible to dysregulated redox signaling and oxidative stress (Fig. 5 ).

5 Summary and Conclusions

Obesity increases the risk of OA at both weight bearing (e.g., knee) and non-
weight bearing (e.g., hand) joints in men and women. These findings suggest a role
for a systemic factor in obesity-associated OA risk. Recent studies have shown that
both knee and hand OA cluster with other metabolic diseases, and although there
are gender and joint-specific differences in these associations, a common link is
excess adiposity. This has lead to an intense interest in understanding how adi-
pokines regulate joint inflammation and tissue homeostasis. Leptin acts as a cat-
abolic mediator of cartilage degeneration in coordination with other inflammatory
factors. Because leptin is associated with knee but not hand OA risk, altered
mechanical loading may function as a critical synergistic pro-inflammatory and
pro-catabolic co-factor to increase cartilage degeneration associated with obesity.
One potential downstream mechanism by which this occurs is an increase in
chondrocyte ROS production. Both pathophysiologic mechanical loading and
inflammation increase mitochondrial ROS production, which under conditions of
metabolic stress up-regulates cartilage matrix catabolism and promotes cell death.
The manner by which obesity affects the local cartilage mechanical environment,
however, is not well understood. Obesity alters knee joint loading in ways that