Department of Orthopaedics, Stony Brook University, Stony Brook, NY 11794, USA.
Department of Orthopedic Surgery, Hospital of Joint Disease, New York University Medical Center, New York, NY 10003, USA.
Osteoarthritis Cartilage. 2016 Nov;24(11):1989-1998. doi: 10.1016/j.joca.2016.06.014. Epub 2016 Jun 27.
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.
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.
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.
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.
软骨是一种对机械刺激高度敏感的组织。软骨细胞会发生一系列复杂的变化，包括增殖和代谢改变，作为外部生物力学和生化刺激的靶点。已知白细胞介素 1β（IL-1β）可调节软骨细胞代谢，在骨关节炎（OA）的发病机制中发挥重要作用。本研究旨在采用低强度脉冲超声（LIPUS）作为局部机械刺激，评估其对软骨细胞迁移、增殖、代谢和分化的影响，以及抑制软骨中 IL-1β介导的分解代谢的能力。
在存在和不存在 IL-1β 的情况下，用 LIPUS 刺激人软骨外植体和软骨细胞，以评估软骨降解、软骨细胞代谢、迁移和增殖。通过 Western blot 分析研究了软骨细胞中与 IL-1β 相关的 NFκB 通路。
LIPUS 刺激增加了人软骨外植体中的蛋白聚糖含量，并抑制了 IL-1β 诱导的蛋白聚糖丢失。LIPUS 刺激增加了软骨细胞的迁移和增殖率，并促进了间充质干细胞（MSC）的软骨生成。此外，LIPUS 抑制了 IL-1β 诱导的 NFκB-p65 和 IĸBα 的磷酸化激活，导致软骨细胞中 MMP13 和 ADAMT5 的表达减少。
综上所述，这些数据表明，LIPUS 通过抑制 IL-1β 的分解代谢作用和刺激软骨细胞迁移、增殖和分化，具有预防软骨降解和治疗 OA 的潜在治疗效果。
