Jason Farrell and Dr. Robert Seegmiller, Department of Physiology and Developmental Biology
Purpose of the Study
The purpose of this study, as also summarized in the proposal for this research grant, was to analyze the temporomandibular joints (TMJs) of mice with a specific collagen defect, Disproportionate Micromelia. Examining these joints was done to provide an animal model to be used in Osteoarthritis research, and to propose a potential mechanism for osteoarthritis in this joint in humans. Better understanding of Osteoarthritis in this joint using an animal model can help lead to potential future treatments for a wide variety of TMJ disorders.
Procedures
In short, mice with the collagen defect and normal mice were compared at different ages, to show differing stages of cartilage degradation in the mutant mice as compared to controls. Craniums were fixed, processed to paraffin sections, stained with Safranin-O and Fast Green, and analyzed with light microscopy. The severity of Osteoarthritis in these joints was quantified using a Mankin scoring procedure that takes into account multiple variables of cartilage degradation and signs of disease. Immunohistochemistry was also performed to look for known Osteoarthritis biomarkers, to better understand what proteins are involved in the progression of disease. Knowing the specific molecules involved can be useful in the creation of targets for therapeutic treatments.
Conclusions
We found that heterozygous mice with this defect are indeed subject to early onset of Osteoarthritis in the TMJ. We saw an up-regulation of biomarkers and condylar cartilage degradation consistent with Osteoarthritis, and thus concluded that this animal model is viable for the study of Osteoarthritis progression in humans. We identified a few key molecules that are expressed in much greater abundance in collagen-defect mice, thus giving insight into the molecular mechanisms of Osteoarthritis.
Reflections on the Project
I am grateful to report that the project did indeed turn out the way we thought. Our hypotheses were shown to be true, and we learned more along the way. We had the opportunity to do a lot of collaboration, and add data to the project that wasn’t in my proposal. I worked very closely with Dr. Kooyman, and we also worked with Laura Bridgewater’s lab. We had no major problems with our project, but I will say that it was a considerable struggle to go through the process of writing our papers, recieveing feedback from journal reviewers, and having to make adjustments. The paper we worked to submit turned out so much different than it was when we started. It was a great experience and humbling, to learn how to take work that I have pride in and completely re-work it. Overall I feel we accomplished all of our goals, and I am very proud of what I’ve been able to accomplish in this project, with the help of an ORCA grant.
Further Results of the Project
There were fantastic results that came from this project, including publications and presentations. Another project I was a part of, heavily referenced in the current project, which was also supported by ORCA grants, was published in the journal Osteoarthritis and Cartilage. A paper from this project was also published, in the journal Archives of Oral Biology. Here are the references with pubmed links:
- D.W. Holt, M.L. Henderson, C.E. Stockdale, J.T. Farrell, D.L. Kooyman, L.C. Bridgewater, R.E. Seegmiller. Osteoarthritis-like changes in the heterozygous sedc mouse associated with the HtrA1–Ddr2–Mmp-13 degradative pathway: a new model of osteoarthritis. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society 1 May 2012 (volume 20 issue 5 Pages 430-439 DOI: 10.1016/j.joca.2011.11.008) Pubmed link: (http://www.ncbi.nlm.nih.gov/pubmed/22155431 )
- M.L. Ricks, J.T. Farrell, D.J. Falk, D.W. Holt, M. Rees, J. Carr, T. Williams, B.A. Nichols, L.C. Bridgewater, P.R. Reynolds, D.L. Kooyman, R.E. Seegmiller. Osteoarthritis in temporomandibular joint of Col2a1 mutant mice. Archives of Oral Biology, Available online 19 March 2013, ISSN 0003-9969, 10.1016/j.archoralbio.2013.02.008. Pubmed link: (http://www.ncbi.nlm.nih.gov/pubmed/23518238)
I also had the opportunity to present this research in a poster session at an international research conference, The Osteoarthritis Research Society International World Congress on Osteoarthritis. I traveled with my mentor, Dr. Seegmiller, Dr. Kooyman, and a few other members of my lab who presented their research, and had the chance to experience what it is like to be a part of contributing knowledge to the world on a particular disease. It was a fantastic experience for me.
In conclusion, I feel grateful to have been part of adding a small portion to the vast, growing pool of knowledge surrounding a very serious, debilitating and misunderstood disease. The experience at the research conference, and being a co-author on two journal publications has also served to enhance my professional life outside of BYU. I’m sure this experience helped me get my current job, working as a research associate for the department of Obstetrics, Gynecology, and Reproductive Sciences at UCSF School of Medicine.