S M Z Uddin1, B Richbourgh2, Y Ding2, A Hettinghouse2, D E Komatsu1, Y-X Qin3, C-J Liu4. 1. Department of Orthopaedics, Stony Brook University, Stony Brook, NY 11794, USA. 2. Department of Orthopedic Surgery, Hospital of Joint Disease, New York University Medical Center, New York, NY 10003, USA. 3. Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA. 4. Department of Orthopedic Surgery, Hospital of Joint Disease, New York University Medical Center, New York, NY 10003, USA. Electronic address: Chuanju.liu@med.nyu.edu.
Abstract
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 plays an important role in the pathogenesis of osteoarthritis (OA). 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 the presence and absence 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 (MSC). 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 OA via a mechanical stimulation that inhibits the catabolic action of IL-1β and stimulates chondrocyte migration, proliferation, and differentiation.
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 plays an important role in the pathogenesis of osteoarthritis (OA). 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:Humancartilage explants and chondrocytes were stimulated by LIPUS in the presence and absence 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 humancartilage 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 (MSC). 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 OA via a mechanical stimulation that inhibits the catabolic action of IL-1β and stimulates chondrocyte migration, proliferation, and differentiation.
Authors: Heikki J Nieminen; Gonçalo Barreto; Mikko A Finnilä; Alejandro García-Pérez; Ari Salmi; Sanjeev Ranjan; Kari K Eklund; Kenneth P H Pritzker; Simo Saarakkala; Edward Hæggström Journal: Sci Rep Date: 2017-06-21 Impact factor: 4.379