Do Certain Biomarkers Accurately Reflect Articular Cartilage Change Due to Physical Activity?
Faculty Mentor: Matthew Seeley, Exercise Sciences
Knee injury and pathology are common problems for Americans who are physically active; they
affect half of all Americans who are over the age of 65, and the related annual costs are nearly
twenty billion dollars. Knee pain alters running and walking neuromechanics1, and may be
deleterious to knee articular cartilage. Researchers have hypothesized that if abnormal gait
mechanics, due to knee pain persist, the resulting mechanical and physiological circumstances
could influence genesis and progression rate of chronic knee joint pathologies, including knee
Certain neuromechanical measures have been used to reflect articular cartilage condition (e.g.,
quadriceps electromyography (EMG), knee flexion angle or external knee addition torque).
However, it is unclear how accurately the neuromechanical measures reflect articular cartilage
morphology and composition.
Various blood biomarkers have also been used to reflect articular cartilage condition. One of the
most studied biomarkers of articular cartilage breakdown and repair is cartilage oligomeric
matrix protein (COMP). This protein is important in maintaining the function of healthy articular
cartilage and has been used in numerous studies to reflect articular cartilage condition for
pathological and healthy individuals.2 However, the relationship of this protein to articular
cartilage condition during physical activity is unclear, during both pain-free and painful physical
Although the evaluation of articular cartilage condition using COMP has been common, the
validation of these markers as reliable biomarkers of knee articular cartilage metabolism or
catabolism in various populations (healthy or pathological) lacks. It should not be assumed that
this systemic (blood and urine-derived) measure represents a phenomenon that occurs at a
specific anatomical location like the knee.
The purpose of this project is to evaluate neuromechanical measures and blood biomarkers
reflecting changes to articular cartilage morphology and composition due to distance running.
Ten male and ten female recreational runners will participate in this study. Participants will
complete four different sessions during the data collection process. During this first session, we
will obtain informed consent and demographic data, screen subjects for contraindications to MRI
examination of the knees, and determine the participant’ preferred running speed. Data
Collection Sessions 2-4 will be completed on three separate days, at the same time of day, 48
hours apart, in a randomized order. Each of these sessions will correspond to a separate
experimental condition: pain, sham, or control.
Speaking generally of Data Collection Sessions 2-4, subjects will arrive at the BYU Magnetic
Resonance Imaging Research Facility (MRIRF) to undergo the pre-run imaging and blood draw
(MRI 1 and Blood Draw 1). This will indicate baseline articular cartilage morphology and
composition, as well as the baseline COMP concentration. Subjects will then be transported to
the BYU Human Performance Research Center to perform a 30-minute run. Throughout the run,
neuromechanical (EMG, and joint kinematics and kinetics) variables will be measured for 30
seconds, every three minutes. After the run, subjects will immediately be transported back to the
BYU MRIRF to undergo MRI 2 (immediately post-run) and Blood Draws 2 and 3 (immediately
post-run and 60 minutes post-run, respectively); these measures will indicate post-run articular
cartilage morphology and composition, as well as post-run COMP concentrations.
Neuromechanic data will be measured with VICON and Visual 3D. Serum COMP
concentrations will be quantified using enzyme-linked immunosorbent assay (ELISA). MRI data
acquisition will be performed using a protocol derived from the Osteoarthritis Initiative (OAI,
We have not yet collected reliable data. Set backs such as the treadmill breaking and adjusting
the methods associated with the MRI have prevented us from starting actual data collection.
Currently, adjustments to the method of collection and analysis of MRI and neuromechanical
data are being made. These adjustments will ensure that the data we collect is both accurate and
Although we have not yet been able to collect or analyze reliable data, I have been accepted in
the BYU Exercise Science Master’s Program and look forward to helping with the project
throughout the next couple of semesters.
During this project I have learned things that will better qualify to do research future. For
example, using different catheters, I have learned how to take blood samples from the antecubital
vein, and how to infuse a saline into the knee infrapatellar fat pad that simulates knee pain. I
have learned how to accurately place reflective markers on the skin that help measure joint
movement. In addition to these technical skills, I have come to better appreciate some of the
common problems that come with research and now better understand how to overcome them.
1. Seeley MK, Park J, King D, Hopkins JT. A novel experimental knee-pain model affects
perceived pain and movement biomechanics. J Athl Train. 2013; 48(3):337-345.
2. Harkey MS, Luc BA, Golightly YM, Thomas AC, Driban JB, Hackney AC, Pietrosimone B.
Osteoarthritis related biomarkers following anterior cruciate ligament injury and reconstruction:
a systematic review. Osteoarthritis Cartilage. 2015; 23(1):1-12.
3 Eckstein, F, M Hudelmaier, and R Putz. “The Effects of Exercise on Human Articular
Cartilage.” Journal of Anatomy 208.4 (2006): 491–512. PMC. Web. 27 Aug. 2016.