Mark Newcomer and Dr. Robert Seegmiller, Biology

The U.S. Department of Health and Human Services cites that nearly 21 million Americans currently suffer from osteoarthritis (OA) and has recently issued a news release which states that, “Today, 35 million people, 13 percent of the U.S. population, are 65 and older, and more than half of them have radiological evidence of osteoarthritis in at least one joint. By 2030, an estimated 20% of Americans – about 70 million people – will have passed their 65th birthday and will be at increased risk of OA.” Arthritis can present itself in many ways and degrees of severity. Osteoarthritis is by far the most prevalent type of arthritis, and is in fact the most common joint disorder in the world. Researchers still do not know the exact causes of OA. There is a great need for a better understanding of the mechanisms that lead to the onset of OA as well as the factors that affect the progression of the disease.

The focus of this study is an analysis of cartilage degeneration, the characterizing feature of OA, but will also assess other structural abnormalities including subchondral sclerosis and the formation of osteophytes. Mice will be the research subjects used for experimentation, specifically a strain of mice that have been bred for a mutation that causes early-onset OA. Another important objective of our study is to further characterize these mice, Disproportionate micromelia (Dmm) mice, as a model for human OA.

Laboratory mice, Mus musulus domesticus, make ideal model organisms for human diseases. Humans are 84% identical to the mouse when the amino acids of the genome are compared. While other animals like orangutans are even more genetically similar, mice are used for their ease to handle, small size, hardiness, and short gestation period. The strain that is used in this study is the Disproportionate micromedia (Dmm) mutant. Mice that are homozygous for the Dmm mutation die at birth from pulmonary hypoplasia caused by the severe skeletal dysplasia that characterizes the mutation. The heterozygous (D/+) mice survive and show early-onset degeneration of the knee and the temporomandibular joints. The wild type of Mouse (+/+) serves as control.

Male and female D/+ mice at three, sic, and nine months of age were used in the study along with their age-matched controls (+/+). A sample size of six male and six female D/+ along with their age-matched controls (+/+) were examined. The right leg of each mouse was dissected for x-ray analysis of the knee joint. The dissected portion of the lef was mounted at an angle of 120 degrees and medial, lateral, and anteroposterior images were taken of each knee joint. Cephalometric radiological equipment provided at the dental office of Gary R. Johnson, DDS (Lisle, IL.) was used to produce the images. The radiographs were then viewed to assess the different structural changes that occur during the progression of OA> In particular I am assessing joint space narrowing, joint fusion, the formation of osteophytes and bone spurs, and joint malalignment.

Through my analysis of the knee joints of mice via x-ray I have noticed various important points of research. Foremost, the maintenance and care of the animals is of vital importance. We came across genotyping troubles in the lab that set back the entire research process. At this point of my research it is important to note that I was given the opportunity to go to the University of Cambridge in England to work on this paper. There a radiologist named Dr. Soh mentored me. He helped me a great deal as we discussed the relationships that my findings may have with OA in humans I stayed at Cambridge for two months and was able to learn a lot from my time with Dr. Soh and have thus included that in this proposal.

The end product we hoped to have for this project was a series of x-rays that showed conclusive evidence whether or not there were signs of OA in the knee joints of mice. The initial x-rays that we took did not provide the desired resolution of the knee joints. The knee joints could not be seen with the greatest of clarity. My mentoring professor and I therefore decided to take digital x-rays since the original x-rays were on plain flat films. I took the digital x-rays at the office of Dr. Young, DDS (Orem, UT). Unfortunately, the digital x-rays didn’t show any bone; the metal pins that I used to set the legs were evident on the x-ray but the knee joint and leg bones were not visible, even on the highest resolution setting.

I now need to go back into my research books and find out how to obtain better x-rays. We were unable to use the original x-rays because the resolution did not show clear formations of osteophytes or even distinguish true joint space measurements. I plan to continue this project and troubleshoot these difficulties with my mentoring professor. When we find better methods for x-raying the knee joints and bones we would like to radiograph the spines of these same mice to look for degeneration as well as the other typical characteristics of OA. If our research is able o find specific patterns in the mice x-rays this evidence can provide vast insight into the onset and degeneration of human. OA.