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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 :
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.
Gilchrist CL, Chen J, Richardson WJ, Loeser RF, Setton LA. Functional integrin subunits regulating cell-matrix interactions in the intervertebral disc. J Orthop Res. 2007 Jun;25(6):829-40.
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.
Ekenstedt KJ, Sonntag WE, Loeser RF, Lindgren BR, Carlson CS. Effects of chronic growth hormone and insulin-like growth factor 1 deficiency on osteoarthritis severity in rat knee joints. Arthritis Rheum. 2006 Dec;54(12):3850-8.
Chubinskaya S, Hakimiyan A, Pacione C, Yanke A, Rappoport L, Aigner T, Rueger DC, Loeser RF. Synergistic effect of IGF-1 and OP-1 on matrix formation by normal and OA chondrocytes cultured in alginate beads. Osteoarthritis Cartilage. 2007 Apr;15(4):421-30. Epub 2006 Nov 27.
Publications:
For a listing of additional publications, refer to PubMed, a service provided by the National Library of Medicine
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