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Biomechanical Signals Suppress Proinflammatory Responses in Cartilage: Early Events in Experimental Antigen-Induced Arthritis¹

Mario Ferretti^2,*, Robert Gassner^2,, Zheng Wang^*, Priyangi Perera^*, James Deschner^*, Gwendolyn Sowa, Robert B. Salter^¶ and Sudha Agarwal^3,*,

^* Section of Oral Biology and Department of Orthopedics, Ohio State University, Columbus, OH 43210; Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15260; Department of Oral and Maxillofacial Surgery, University of Innsbruck, Innsbruck, Austria; and ^¶ Hospital for Sick Children, Toronto, Canada

Although biomechanical signals generated during joint mobilization are vital in maintaining integrity of inflamed cartilage, the molecular mechanisms of their actions are little understood. In an experimental model of arthritis, we demonstrate that biomechanical signals are potent anti-inflammatory signals that repress transcriptional activation of proinflammatory genes and augment expression of anti-inflammatory cytokine IL-10 to profoundly attenuate localized joint inflammation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants HD40939 (National Institute of Child Health and Human Development), AR48781 (National Institute of Arthritis and Musculoskeletal and Skin Diseases), and AT0006646 (National Center for Complementary and Alternative Medicine).

² M.F. and R.G. share equal first authorship.

³ Address correspondence and reprint requests to Dr. Sudha Agarwal at the current address: Biomechanics and Tissue Engineering Laboratory, 4171 Postle Hall, Ohio State University, 305 West 12th Avenue, Columbus, OH 43210. E-mail address: Agarwal.61{at}osu.edu

⁴ Abbreviations used in this paper: RA, rheumatoid arthritis; OA, osteoarthritis; AIA, Ag-induced arthritis; CPM, continuous passive motion; IMM, immobilization; COX, cyclooxygenase; MMP, matrix metalloproteinase; SF, synovial fluid; FM, free movement; PMN, polymorphonuclear cell.

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