Research Interests: Lab: The cellular and molecular mechanisms that regulate cartilage destruction in osteoarthritis and the role of aging. Clinical: The genetics of osteoarthritis; exercise and weight loss interventions for osteoarthritis. Current Research: Osteoarthritis is characterized by a progressive breakdown and loss of articular cartilage that is mediated by an imbalance in chondrocyte catabolic and anabolic activity. Our lab studies the basic mechanisms responsible, with a focus on cell signaling that results from growth factor and integrin stimulation of human articular chondrocytes. We are determining how aging contributes to chondrocyte resistance to the anabolic growth factor IGF-I, including the role of age-related oxidative stress. A second project examines the function of a family of cell-matrix receptors called integrins. Recent work has focused on cell signaling pathways activated through integrins which regulate cell survival and matrix metalloproteinase (MMP) expression. Current clinical studies include participation in a multi-center clinical study to discover the genes which are associated with the development of generalized osteoarthritis and studies on the role of diet and exercise for osteoarthritis. Recent Publications: Loeser, RF. Articular cartilage nuclear receptors: an emerging target for treatment of osteoarthritis. Osteoarthritis Cartilage 2009 April 22. Loeser RF. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthritis Cartilage. 2009 Mar 12 Yammani RR, Long D, Loeser, RF. Interleukin-7 stimulates secretion of S100A4 by activating the JAK/STAT signaling pathway in human articular chondrocytes. Arthritis Rheum. 2009 Mar;60(3):792-800. Cravero JD, Carlson CS, Im HJ, Yammani RR, Long D, Loeser RF. Increased expression of the Akt?PKB inhibitor TRB3 in osteoarthritic chondrobytes inhibils insulin-like groth factor 1-mediated cell survival and proteoglycan synthesis. Arthritis Rheum. 2009 Feb;60(2):492-500. Loeser RF, Im HJ, Richardson B, Lu Q, Chubinskaya S. Methylation of the OP-1 promoter: potential role in the age-related decline in OP-1 expression in cartilage. Osteoarthritis Cartilage. 2009 Apr;17(4):513-7.Epub 2009 Sept 30. Loeser R. Molecular mechanisms of cartilage destruction in osteoarthritis. J Musculoskelet Neuronal Interact. 2008 Oct-Dec;8(4):303-6. Loeser R, Translational research in osteoarthritis-from molecules to animals to humans. J Musculoskelet Neuronal Interact. 2008 Oct-Dec;8(4):301-2. Atif U, Philip A, Aponte J, Woldu EM, Brady S, Kraus VB, Jordan JM, Doherty M, Wilson AG, Loeser R.Absence of association of aspirin polymorphisms and osteoarthritis susceptibility in US Caucasians. Osteoarthritis Cartilage 2008;16(10):1174-1177. Chua SD, Messier SP, Legault C, Lenz ME, Thonar E J-M, Loeser RF. Effect of an exercise and dietary intervention on serum biomarkers in overweight and obese adults with osteoarthritis of the knee. Osteoarthritis and Cartilage 2008; 16: 1047-1053. Long D, Blake S, Song X-Y, Lark M, Loeser RF. Human articular chondrocytes produce IL-7 and respond to IL-7 with increased production of MMP-13. Arthritis Res Ther 2008;10:R23. Loeser RF, Erickson EA, Long DL. Mitogen-activated protein kinases as therapeutic targets in osteoarthritis. Curr Opin Rheumatol 2008;20:581-6. Del Carlo M, Schwartz D, Erickson EA, Loeser RF. Endogenous production of reactive oxygen species is required for stimulation of human articular chondrocyte matrix metalloproteinase production by fibronectin fragments. Free Radic Biol Med. 2007 May 1;42(9):1350-8. Epub 2007 Jan 24. Im HJ, Muddasani P, Natarajan V, Schmid TM, Block JA, Davis F, van Wijnen AJ, Loeser RF. Basic fibroblast growth factor stimulates matrix metalloproteinase-13 via the molecular cross-talk between the mitogen-activated protein kinases and protein kinase Cdelta pathways in human adult articular chondrocytes. J Biol Chem. 2007 Apr 13;282(15):11110-21. Epub 2007 Feb 20. Publications:
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