R Parekh1, M K Lorenzo2, S Y Shin3, A Pozzi4, A L Clark5. 1. Faculty of Science, The University of Calgary, Calgary, AB, Canada. Electronic address: parekhr@ucalgary.ca. 2. Faculty of Science, The University of Calgary, Calgary, AB, Canada. Electronic address: mklorenz@ucalgary.ca. 3. Faculty of Kinesiology, The University of Calgary, Calgary, AB, Canada. Electronic address: ssy080@gmail.com. 4. Department of Medicine, Vanderbilt University, Nashville, TN, USA; Department of Medicine, Veterans Affairs Hospital, Nashville, TN, USA. Electronic address: ambra.pozzi@vanderbilt.edu. 5. Faculty of Kinesiology, The University of Calgary, Calgary, AB, Canada; Department of Surgery, Faculty of Medicine, The University of Calgary, Calgary, AB, Canada. Electronic address: alclark@ucalgary.ca.
Abstract
OBJECTIVE: To elucidate the role of integrin α1β1 in chondrocyte responses to inflammatory interleukin-1α (IL-1) and anabolic transforming growth factor-β1 (TGF-β1) in the knee. METHODS: Intracellular calcium transient responses to IL-1 and TGF-β1 were measured in wild type and integrin α1-null chondrocytes using real time ex vivo confocal microscopy, and immunohistochemistry was performed to analyze TGF-β1-mediated activation of Smad2/3 in tibial and femoral chondrocytes. RESULTS: Loss of integrin α1β1 reduces intracellular calcium transient response to IL-1, while it enhances chondrocyte responses to TGF-β1 as measured by intracellular calcium transients and activation of downstream Smad2/3. CONCLUSIONS: Integrin α1β1 plays a vital role in mediating chondrocyte responses to two contrasting factors that are critical players in the onset and progression of osteoarthritis - inflammatory IL-1 and anabolic TGF-β. Further investigation into the molecular mechanisms by which integrin α1β1 mediates these responses will be an important next step in understanding the influence of increased expression of integrin α1β1 during the early stages of osteoarthritis on disease progression.
OBJECTIVE: To elucidate the role of integrin α1β1 in chondrocyte responses to inflammatory interleukin-1α (IL-1) and anabolic transforming growth factor-β1 (TGF-β1) in the knee. METHODS: Intracellular calcium transient responses to IL-1 and TGF-β1 were measured in wild type and integrin α1-null chondrocytes using real time ex vivo confocal microscopy, and immunohistochemistry was performed to analyze TGF-β1-mediated activation of Smad2/3 in tibial and femoral chondrocytes. RESULTS: Loss of integrin α1β1 reduces intracellular calcium transient response to IL-1, while it enhances chondrocyte responses to TGF-β1 as measured by intracellular calcium transients and activation of downstream Smad2/3. CONCLUSIONS: Integrin α1β1 plays a vital role in mediating chondrocyte responses to two contrasting factors that are critical players in the onset and progression of osteoarthritis - inflammatory IL-1 and anabolic TGF-β. Further investigation into the molecular mechanisms by which integrin α1β1 mediates these responses will be an important next step in understanding the influence of increased expression of integrin α1β1 during the early stages of osteoarthritis on disease progression.
Authors: Bridgette D Furman; Jens Strand; W Chad Hembree; Benjamin D Ward; Farshid Guilak; Steven A Olson Journal: J Orthop Res Date: 2007-05 Impact factor: 3.494