Chondro-Protective Effects of Low Intensity Pulsed Ultrasound. Author: Uddin SM1, Richbourgh B2, Ding Y2, Hettinghouse A2, Komatsu DE1, Qin YX3, Liu C4 Affiliation: <sup>1</sup>Department of Orthopaedics, Stony Brook University, Stony Brook, NY 11794. <sup>2</sup>Department of Orthopedic Surgery, Hospital of Joint Disease, New York University Medical Center, New York, NY 10003. <sup>3</sup>Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794. <sup>4</sup>Department of Orthopedic Surgery, Hospital of Joint Disease, New York University Medical Center, New York, NY 10003. Electronic address: Chuanju.liu@med.nyu.edu. Conference/Journal: Osteoarthritis Cartilage. Date published: 2016 Jun 27 Other: Pages: S1063-4584(16)30148-0 , Special Notes: doi: 10.1016/j.joca.2016.06.014. [Epub ahead of print] , Word Count: 246 OBJECTIVES: Cartilage is a highly mechano-responsive tissue. Chondrocytes undergo a series of complex changes, including proliferation and metabolic alteration as the target of external biomechanical and biochemical stimuli. IL-1β is known to regulate chondrocyte metabolism and play an important role in the pathogenesis of osteoarthritis. The objective of this study was to employ low-intensity pulsed ultrasound (LIPUS) as a localized mechanical stimulus and assess its effects on chondrocyte migration, proliferation, metabolism, and differentiation, as well as its ability to suppress IL-1β mediated catabolism in cartilage. METHODS: Human cartilage explants and chondrocytes were stimulated by LIPUS in presence and absence of of IL-1β to asses cartilage degradation, chondrocytes metabolism, migration and proliferation. Western blot analyses were conducted to study IL-1β the associated NFκB pathway in chondrocytes. RESULTS: LIPUS stimulation increased the proteoglycan content in human cartilage explants and inhibited IL-1β induced loss of proteoglycans. LIPUS stimulation increased rates of chondrocyte migration and proliferation, and promoted chondrogenesis in mesenchymal stem cells. Further, LIPUS suppressed IL-1β induced activation of phosphorylation of NFκB-p65 and IĸBα leading to reduced expression of MMP13 and ADAMT5 in chondrocytes. CONCLUSIONS: Collectively, these data demonstrate the potential therapeutic effects of LIPUS in preventing cartilage degradation and treating osteoarthritis via a mechanical stimulation that inhibits the catabolic action of IL-1β and stimulates chondrocyte migration, proliferation, and differentiation. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. KEYWORDS: Cartilage Metabolism; Chondrocytes; Interleukin 1β; Low Intensity Pulsed Ultrasound; Osteoarthritis PMID: 27364595 DOI: 10.1016/j.joca.2016.06.014