Biomedical Engineering Reference
In-Depth Information
cartilage strains in the tibial plateau but not the femoral condyles or femoral
groove [ 42 ]. These findings show that the effects of a high BMI on the local
cartilage mechanical environment are site-specific. Future studies that span a wider
range of BMI values and include a more representative sample of obese individ-
uals with lower daily step counts compared to lean individuals will provide
important functional insight into the effect of obesity on the local cartilage
mechanical environment. Advances in functional MRI techniques to assess
changes in cartilage proteoglycan content will further enhance our understanding
of how joint loading characteristics impact the local mechanical environment
during disease conditions such as obesity and OA [ 43 ].
In summary, obesity alters knee joint loading in ways that appear to both
increase and decrease joint stresses. Medial-lateral joint stresses are altered with
obesity due to limb malalignment and dynamic gait changes. These changes
increase the knee adduction moment with obesity and aging. However, overall
physical activity levels are greatly reduced with obesity. Thus, it is difficult to
predict how obesity affects the local cartilage mechanical environment. Recent
advances in the use of MRI to quantify in vivo diurnal strains in normal-weight,
overweight, and obese individuals are providing new insight into the net effect of
BMI on articular cartilage deformation. Understanding how chondrocytes alter
cartilage material properties and cartilage thickness in response to mechanical
stress, and how this responsiveness is impaired with obesity and aging, is
important for understanding the underlying causes of OA. The following sections
will review how obesity and aging impair chondrocyte homeostasis by activating
cellular stress pathways and impairing cellular defense pathways. Examples where
mechanical signals have been shown to mediate these responses will be discussed.
3 Obesity and Inflammation
3.1 Systemic Versus Local Factors
Excess adiposity, particularly visceral fat, is associated with increased systemic
inflammation, increased risk of metabolic syndrome, and increased risk of knee OA
[ 44 , 45 ]. However, the specific role of systemic inflammatory factors in knee OA
pathogenesis is not well understood due to the challenge of isolating the biome-
chanical aspects of aging and obesity from the inflammatory changes [ 46 ]. OA is a
multi-factorial disease, and biomechanical and inflammatory factors converge at the
cellular level on a common set of developmental and catabolic signaling pathways
in cartilage [ 3 , 47 ]. Moreover, there is uncertainty about the relationship between
systemic and local inflammation, in part due to an insufficient understanding of how
joint tissues, such as the infrapatellar fat pad and the synovium, contribute to
intra-articular inflammation relative to systemic inflammatory mediators. Some
inflammatory cytokines and adipokines (i.e., adipose-tissue derived cytokines and
chemokines) are found in greater concentrations in synovial fluid compared to
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