Joint Biomechanics

Joint and Whole Body Studies

At the joint and whole body levels, the development of non-invasive or minimally-invasive methods to quantify skeletal differentiation, morphology, composition, structure, and mechanical function.

These studies include:

Etiology of joint injuries in activity and sports

Various structures in the joints play important roles in joint stabilization and prevention of cartilage injury that could lead to degenerative osteoarthritis. Among such structures is the meniscus in the knee joints and various ligamentous tissues in the knee and hip joints.

Through collaborations with clinicians including Drs. Thomas Vail and Steve Olson and other scientists including Dr. Lori Setton, we are able to study the effects of injury or surgical resection of such structures on articular cartilage degeneration. These studies help us improve our understanding of the etiology of joint injury during activity, sports, or follwoing surgical procedures.
Menisectomy and Joint Degeneration

References:
- Francisco, A.C., Nightingale, R.W., Guilak, F., Glisson, R.R., and Garrett, W.E. (2000): Comparisons of soccer shin guards in preventing tibia fracture. American Journal of Sports Medicine, 28(2):227-233.
- Hewitt, J.D., Guilak, F., Glisson, R.R., and Vail, T.P.: (2001) Regional material properties of the human hip joint capsule ligaments. Journal of Orthopaedic Research, 19(3):359-364.
- Elliott, D.M., Jones, R., Setton, L.A., Scully, S.P., Vail, T.P., and Guilak, F. (2001): Chondroprotective effects of meniscal allograft transplantation. Knee Surgery, Sports Traumatololgy, Arthroscopy
- Wyland DJ. Guilak F. Elliott DM. Setton LA. Vail TP. Chondropathy after meniscal tear or partial meniscectomy in a canine model. Journal of Orthopaedic Research. 20(5):996-1002, 2002.

Biochemical markers of OA in synovial fluid

Synovial fluid biochemical markers (or, biomarkers) are molecules that enter the joint fluid, presumably as a result of cartilage and synovium metabolism. These proteins are thought to reflect the metabolic state of the articular cartilage and may serve as surrogate markers for the severity of arthritis in humans and animals.

Through collaborations with Dr. Virginia Kraus and other colleagues, new methods for quantifying joint fluid biomarker concentrations in a manner that corrected for dilutional effects of the lavage procedure were developed based on urea, a molecule that is niether synthesized nor metabolized in the joint.

These collaborative efforts provided robust methods for quantifying biomarkers for OA that can be used in the clinical laboratories.

Biomarkers of OA

References:
- Lindhorst, E., Vail, T.P., Guilak, F., Wang, H., Setton, L.A., Vilim, V., and Kraus, V.B. (2000): Longitudinal characterization of synovial fluid biomarkers in the canine meniscectomy model of osteoarthritis. Journal of Orthopaedic Research, 18(2):269-280.
- Carlson, C.S., Guilak, F., Vail, T.P., and Kraus, V.B. (2002): Synovial fluid biomarkers as predictors of histologic changes in articular cartilage following meniscectomy. Journal of Orthopaedic Research, 20(1):92-100.
- Kraus VB, Huebner JL, Fink C, King JB, Brown S, Vail TP, Guilak F (2002): Urea as a passive transport marker for arthritis biomarker studies. Arthritis Rheum. 46(2):420-427.

Role of Collagen Type VI in Chondrons and Cartilage

Extracellular component play integral roles in determining the mechanical properties of tissues such as cartilage. One such component, type VI collagen, is postulated to play an important role in the biomechanical properties of the pericellular matrix (PCM) of chondrocytes. Using collagen type VI knockout mice we are comparing the mechanical properties of chondrons with and without type VI collagen. These studies are coupled with qualitative and semi-quantitative histology to determine if mice lacking collagen VI exhibit changes in joint structure that are characteristic of OA. A link between mechanics, structure, function, and disease is sought.
Collagen VI
References:
- Leonidas G Alexopoulos, Gregory M Williams, Maureen L Upton, Lori A Setton, Farshid Guilak: The Biomechanical Role of the Chondrocyte Pericellular Matrix. Trans 50th Annu Meet Orthop Res Soc, San Francisco, CA. 29: 523, 2004.


Skeletal Phenotyping of Genetically Altered Mice

Through collaborations with various scientists, including Dr. Darryl Quarles and others, we are beginning to study models of human skeletal disease using genetically modified mice. These skeletal phenotyping studies utilize non-invasive live animal imaging using 2D dual energy x-ray (DEXA) and 3D quantitative micro-CT, histologic and histomorphometric analysis of un-decalcified tissue, DNA analysis using RT-PCR, immunolocalization of cartilage and bone specific marker proteins using in situ hybridization techniques, biochemical analysis of serum and urine, and biomechanical testing. These genetically altered animal models also offer novel and exciting opportunities to study the roles that certain deleted or altered genes play in specific differentiation pathways (e.g. Sox9 in chondrogenesis) or the role of specific proteins (e.g. Collagen VI) in the integrity of cartilage mechanical function.
Skeletal Phenotyping

References:
- Fink, C., Cooper J., Heubner, J.L., Guilak, F., and Kraus, V.B. (2002): Precision and accuracy of a transportable dual-energy x-ray absorptiometry unit for bone mineral measurements in guinea pigs. Calcified Tissue International, published online January 21, 2002.
- Liu S, Brown TA, Xiao Z, Guo R, Awad HA, Guilak F, Quarles LD: Deletion of Mepe in Hyp Mice Fails to Correct Hypophosphatemia but Partially Rescues Abnormal Mineralization in Osteoblasts Ex Vivo. J Bone Min Res, 2004 (In Preparation)