PROJECT SUMMARY
Excessive compressive load caused by blunt impact to the knee, such as during a car accident or sports injury,
is known to lead to osteoarthritis (OA) within the joint. Often times, no gross ligament or meniscal damage is
present in these cases; given this, occult damage is not treated, representing an underserved opportunity to
prevent later pathology. Our laboratory previously developed a model, using the Flemish Giant rabbit, to study
the effects of impact compressive loading to the knee. This model has shown that blunt impacts result in: (i)
cartilage damage; (ii) microcracks at the interface between calcified cartilage and underlying subchondral bone
in the tibial plateau; and (iii) significant loss of glycosaminoglycans in the meniscal tissue, all of which point to
clinical signs of post-traumatic osteoarthritis (PTOA). Interestingly, recent studies by our group using the Hartley
guinea pig model of spontaneous OA have shown that early removal of the infrapatellar fat pad (IFP) was able
to prevent progression of pathology (i.e. histopathology and micro-computer tomography scores were reduced
in the limbs with the IFP removed compared to sham control). Improvement in limbs was attributed to the
development of a replacement fibrous connective tissue (FCT) in place of the IFP, which demonstrated less
evidence of inflammation and fewer changes in material properties of joint tissues than the native adipose depot.
Given this, the goal of the present study is to further elucidate the role of the IFP in PTOA development in our
Flemish Giant rabbit model of compressive loading. We propose to determine the role that injured IFP plays in
knee degeneration and identify whether biomechanical and/or molecular pathways may be influencing the
development of PTOA post-injury. We hypothesize that removal of the IFP will prevent/decrease PTOA
following blunt impact to the knee. We will accomplish this via two subaims: (1) Correlate the presence and
severity of PTOA to the tissue distribution of inflammatory/pathologic mediators in the joint. Proposed work will
quantitate the presence of key inflammatory and matrix degrading molecules in joint tissues, serum (systemic
changes), and synovial fluid (local changes) via proteomics and metabolomics. (2) Assess the biomechanical
properties of the bone, cartilage, and menisci following removal of the IFP. Biomechanical properties of joint
tissue will be characterized using: cranial drawer tests; tensile tests, which will evaluate the time dependent and
failure properties of the whole knee joint; macro-indentation testing of articular cartilage, menisci, IFP, and FCT,
which will establish the comparative stiffness of these structures; and shear and compression testing of the IFP
and FCT to determine material behavior. By pursuing this mechanistic rationale to explain the negative
ramifications of the IFP on knee joint health, our work may support early removal of the IFP in patients who have
suffered a blunt trauma to the knee joint. Our dual approach will be helmed by a uniquely qualified research team
with demonstrated productivity. Additionally, this project will train undergraduates in multi-disciplinary research
ranging from molecular mechanisms to engineering.
