Background

• Premature knee osteoarthritis has been associated with kinematic changes during walking following conditions such as ACL injury.
• Kinematic changes can shift cyclic loading during walking to regions of the cartilage that are not conditioned to respond to such loading.
• Elevated systemic levels of inflammatory markers often precede the development of OA and can interact negatively with mechanical load.

Goals

• To investigate regional dependence on the biological response of cartilage to loading by testing the relationship between loading and cellular response (i.e. gene expression and protein synthesis) in different regions (central and peripheral) of tibial cartilage of a porcine knee.
• To investigate whether an introduced inflammatory marker (TNF-α) in combination with load can produce a degradative response.

Major Findings

• Cartilage samples from central and peripheral regions express different levels of structural proteins for the same loading (Figure) [1].
• Adding TNF-α to mechanical load initiates a degradative response that is also region dependent [2].

Implications

• These regional biological variations of cartilage in response to a mechanical load suggest that cartilage health at the knee can be sensitive to conditions that cause kinematic changes during walking, such as an ACL or meniscus injury.
• Elevated levels of inflammatory markers combined with kinematic changes can elevate the risk of developing clinical knee osteoarthritis.
• These results support a kinematic pathway to knee osteoarthritis.

Representative Publications

1. Central and peripheral region tibial plateau chondrocytes respond differently to in vitro dynamic compression.
   Bevill SL, Briant PL, Levenston ME, Andriacchi TP. Osteoarthritis Cartilage. 2009 Aug;17(8):980-7.
2. The regional sensitivity of chondrocyte gene expression to coactive mechanical load and exogenous TNF-a stimuli.
   Bevill S, Boyer K, Andriacchi T. J. Biomech Eng. 2014 Sep;136(9):091005.

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