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 can act like an organ and deregulate the body’s inflammation response chemically.
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 inflammatory 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 stress and inflammation, we believe, will help paint a more complete picture of how obesity contributes to arthritis.
In addition to studying the relationship between arthritis 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, which often leads to worsening pain in the joints. We want to better understand this vicious cycle and find out if there’s a way to break it, allowing people to be more active, reduce obesity and live 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 altered joint loading regulate articular cartilage homeostasis via effects on chondrocyte mitochondrial function and free radical biology. We are particularly interested in the role of nitric oxide as a signaling molecule for genes that regulate cell metabolism and oxidative stress responses, such as peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1α).
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), we hope to reveal novel pathways that regulate cartilage matrix homeostasis. Furthermore, by examining behavioral outcomes in our animal models that are associated with altered motor function and pain, we seek to identify the pathologic mechanisms linking obesity to clinically relevant outcome measures. These studies will also provide a basis for examining how therapeutic interventions that target inflammatory and oxidative processes affect joint-specific pathophysiology and behavioral 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: 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.
Bhaskaran S, Pharaoh G, Ranjit R, Murphy A, Matsuzaki S, Nair BC, Forbes B, Gispert S, Auburger G, Humphries KM, Kinter M, Griffin TM, Deepa SS. Loss of mitochondrial protease ClpP protects mice from diet-induced obesity and insulin resistance. EMBO Rep. 2018 Mar;19(3). Epub 2018 Feb 2. PMID: 29420235
He C, Medley SC, Kim J, Sun C, Kwon HR, Sakashita H, Pincu Y, Yao L, Eppard D, Dai B, Berry WL, Griffin TM, Olson LE. STAT1 modulates tissue wasting or overgrowth downstream from PDGFRβ. Genes Dev. 2017 Aug 15;31(16):1666-1678. Epub 2017 Sep 18. PMID: 28924035
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):760-769. Epub 2017 Oct 17. PMID: 28892196
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 Feb 11. [Epub ahead of print] [Abstract]
Griffin TM, Humphries KM, Kinter M, Lim HY, Szweda LI. Nutrient sensing and utilization: Getting to the heart of metabolic flexibility. Biochimie. 2016 May;124:74-83. Epub 2015 Oct 22. Review. [Abstract]
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. 2015 Oct 8. pii: glv151. [Epub ahead of print] [Abstract]
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 [Abstract]
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]
Cai, A; Hutchison, E; Hudson, J; Kawashima, Y; Komori, N; Singh, A; Brush, RS; Anderson, RE; Sonntag, WE; Matsumoto, H*; Griffin, TM*. Metabolic enrichment of omega-3 polyunsaturated fatty acids does not reduce the onset of idiopathic knee osteoarthritis in mice. Osteoarthritis Cartilage. 2014 22:1301-1309. *co-corresponding authors. PMCID: PMC4150746
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
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. […]