Obesity is a major risk factor for osteoarthritis, the most common form of arthritis and a leading cause of disability in the U.S. Although conventional wisdom holds that increased pressure on joints from carrying excess weight causes osteoarthritis, this is far from a complete answer. Recent discoveries suggest that fat itself is a critical mediator of the disease. Fat is not just excess energy from food hanging around your waist. Rather, fat acts like an organ by releasing molecules that affect how the body functions. When the body has too much fat, it can release molecules that activate immune cells and cause inflammation.
My lab is studying how obesity contributes to the development of osteoarthritis by studying how changes in joint pressure and inflammation associated with excess fat contribute to the disease process. We are also studying how these changes impact the metabolic machinery of tissues within the joint, such as cartilage. Understanding how excess fat alters both joint inflammation and metabolism, we believe, will lead to new treatment strategies by painting a more complete picture of how obesity contributes to osteoarthritis.
In addition to studying the relationship between osteoarthritis and obesity, we’re also looking at a third component—exercise. Pain caused by osteoarthritis keeps people from leading active lifestyles. This then contributes to obesity and other chronic diseases, such as cardiovascular disease and diabetes. Exercise is the best way to break this vicious cycle of joint pain and chronic disease. We're studying how exercise breaks this cycle at the cellular level to develop new options for people to live more active lives without the pain of arthritis.
Osteoarthritis is a disease characterized by cartilage destruction and abnormal bone growth resulting in joint pain and severe disability. It is the primary cause of disability in the United States, and it contributes significantly to reductions in health that occur with aging. Although osteoarthritis is often considered an inevitable consequence of aging, numerous genetic and environment risk factors have been identified that mediate its occurrence and severity. One of the most significant and modifiable risk factors is obesity.
Our laboratory uses integrative and interdisciplinary approaches to study how obesity dysregulates biomechanical, inflammatory, and metabolic processes that are associated with the development of osteoarthritis. We are seeking to determine how dietary fats, adipokines (e.g., leptin), and cyclic joint loading regulate articular cartilage homeostasis via effects on chondrocyte mitochondrial function and free radical biology. We are particularly interested in the role of sirtuins (e.g., Sirt3) as regulators of cellular metabolism and oxidative stress responses that help maintain chondrocyte function during aging, obesity, and injury. In addition, we are investigating how intra-articular adipose tissue modulates joint inflammation by altering the metabolic environment of the joint.
We are also interested in understanding how physical activity interacts with obesity-related phenotypes to regulate these processes in healthy and diseased tissue. Therefore, we use a variety of models spanning multiple levels of organization (e.g., cell, tissue, and animal) to study the effect of voluntary exercise (in vivo) and controlled biomechanical loading regimes (in vitro) on inflammatory, metabolic, and anti-oxidant processes in cartilage.
By studying the interaction of diet and physical activity (i.e., two modifiable risk factors for obesity) during aging, we hope to reveal novel pathways that regulate cartilage matrix homeostasis. Furthermore, by examining behavioral changes in our animal models that are associated with motor function and pain, we emphasize clinically relevant outcome measures so that we can better translate our finding to patients. These studies provide a basis for examining how therapeutic interventions that target inflammatory, metabolic, or oxidative processes affect joint-specific pathophysiology and functional outcomes.
B.A., Harvard University, Cambridge, MA, 1996
Ph.D., University of California, Berkeley, CA, 2002
Postdoc, Duke University Medical Center, Durham, NC, 2002–2007
Honors and Awards
2016 Fred Jones Award for Scientific Achievement, Oklahoma Medical Research Foundation
2010 Top 10 Arthritis Advances, Arthritis Foundation
2010 Melba M. O’Connell Memorial Fellow, Arthritis National Research Foundation
2007 Outstanding Postdoc Award, Duke University
2007 Young Investigator Award, Osteoarthritis Research Society International (OARSI) World Congress on Osteoarthritis
2007 Hulda Irene Duggan Arthritis Investigator Award, Arthritis Foundation
2004 NIH Ruth L. Kirschstein National Research Service Award (NIAMS)
2003 New Investigator Award, American Physiological Society
2016 - present: Associate Editor, Osteoarthritis and Cartilage
2017 - present: Ad hoc reviewer, SBSR Study Section (NIH)
2016 - present: Editorial Board Member, Osteoarthritis and Cartilage
2015: Section Leader (OA Laboratory Grants), Arthritis Foundation's Delivering on Discovery Peer Review
2015-present: Member, NIH NIAMS Biospecimen Review and Allocation Committee for the Osteoarthritis Initiative
2014-2016: Co-chair, Cartilage, Synovium & Osteoarthritis Topic Committee, Orthopaedic Research Society
2013-2016: Advisory Editor, Arthritis & Rheumatology
2013: Invited Participant, NIH NIAMS Roundtable on OA and Inflammation
American Physiological Society
Orthopaedic Research Society
Osteoarthritis Research Society International
Joined OMRF Scientific Staff in 2008.
Griffin TM, Batushansky A, Hudson J, Lopes EBP. Correlation network analysis shows divergent effects of a long-term, high-fat diet and exercise on early stage osteoarthritis phenotypes in mice. J Sport Health Sci 9:119-131, 2020 March, PMID: 32099720, PMCID: PMC7031811
Griffin TM, Friedman JE. How can parental obesity promote OA across generations? Nat Rev Rheumatol, 2020 January, PMID: 31949286
Issa R, Boeving M, Kinter M, Griffin TM. Effect of biomechanical stress on endogenous antioxidant networks in bovine articular cartilage. J Orthop Res. 2018 Feb; 36(2):760–9. PMID: 28892196 PMCID: 5839935
Fu Y, Kinter M, Hudson J, Humphries KM, Lane RS, White JR, Hakim M, Pan Y, Verdin E, Griffin TM. Aging promotes SIRT3-dependent cartilage SOD2 acetylation and osteoarthritis. Arthritis Rheumatol. 2016 Aug;68(8):1887-98. PMID: 26866626 PMCID: PMC5331855
Fu Y, Huebner JL, Kraus VB, Griffin TM. Effect of aging on adipose tissue inflammation in the knee joints of F344BN Rats. J Gerontol A Biol Sci Med Sci. 2016 Sep;71(9):1131-40. PMID: 26450946 PMCID: PMC4978355
Lane RS, Fu Y, Matsuzaki S, Kinter M, Humphries KM, Griffin TM. Mitochondrial respiration and redox coupling in articular chondrocytes. Arthritis Res Ther. 2015 Mar 10;17:54. PMID: 25889867 PMCID: PMC4384316
Fu Y, Griffin TM. Obesity, Osteoarthritis, and Aging: The Biomechanical Links. The Mechanobiology of Obesity and Related Diseases, Ed. Gefen A, Benayahu, D. Series: Studies in Mechanobiology, Tissue Engineering and Biomaterials. Springer, 2014. 16:181-201. [Chapter]
Aging & Metabolism Research Program, MS 21
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-7579
Fax: (405) 271-1437
Padmaja Mehta D'souza, Ph.D.
Ravi Komaravolu, Ph.D.
Albert Batushansky, Ph.D.
Assistant Staff Scientist
Shouan Zhu, Ph.D.
Senior Research Technician
Research Trainee (Polish Student Exchange Program)
Research Trainee (Polish Student Exchange Program)
News from the Griffin lab
A new wave of researchers has joined the Oklahoma Medical Research Foundation’s scientific staff as part of the foundation’s expansion. OMRF has added seven new scientists to its staff. In addition, two research assistants have been promoted to faculty-level positions. The new researchers have come to OMRF from a variety of institutions across the U.S. […]