Anti‐inflammatory effects of continuous passive motion on meniscal fibrocartilage

Abstract

Motion-based therapies have been applied to promote healing of arthritic joints. The goal of the current study was to determine the early molecular events that are responsible for the beneficial actions of motion-based therapies on meniscal fibrocartilage. Rabbit knees with Antigen-InducedArthritis (AIA) were exposed to continuous passive motion (CPM) for 24 or 48 h and compared to immobilized knees. The menisci were harvested and glycosaminoglycans (GAG), interleukin-1β (IL-1β), matrix metalloproteinase-1 (MMP-1), cyclooxygenase-2 (COX-2), and interleukin-10 (IL-10) were determined by histochemical analysis.Within 24 h, immobilized knees exhibited marked GAG degradation. The expression of proinflammatory mediators MMP-1, COX-2, and IL-1β was notably increased within 24 h and continued to increase during the next 24 h in immobilized knees. Knees subjected to CPM revealed a rapid and sustained decrease in GAG degradation and the expression of all proinflammatory mediators during the entire period of CPM treatment. More importantly, CPM induced synthesis of the anti-inflammatory cytokine IL-10. The results demonstrate that mechanical signals generated by CPM exert potent anti-inflammatory signals on meniscal fibrochondrocytes. Furthermore, these studies explain the molecular basis of the beneficial effects of CPM observed on articular cartilage and suggest that CPM suppresses the inflammatory process of arthritis more efficiently than immobilization.

Dynamic Biomechanical Strain Inhibits IL-1β–induced Inflammation in Vocal Fold Fibroblasts

“…14 Emerging evidence emphasizes, that in other tissues, cyclic tensile strain (CTS) of low/ physiological magnitudes attenuates the inflammatory response and augments repair by inducing synthesis of extracellular matrix in vitro 15 and in vivo. 16 For example, interleukin-1β (IL-1β), a proinflammatory cytokine in secretions localized to the surface of injured vocal folds, 17,18 induces synthesis of a plethora of proinflammatory mediators including inducible-nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin-E 2 (PGE 2 ), and matrix metalloproteinases (MMPs) in mesenchymal cells including, cartilage, tendons, and osteoblast-like cells of the periodontal ligament. However, cyclic tensile strain at low/physiological magnitudes inhibits IL-1β-induced synthesis of all of the above mediators, significantly.…”

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

“…The histopathogenesis of AIA has been well-characterized and the model demonstrates many features of human RA, including joint inflammation and damage to articular cartilage via both increased breakdown and decreased synthesis of the cartilaginous matrix (15,20). Using this model, we document that CPM attenuates AIA-induced inflammation in the cartilage.…”

Regulation of Chondrocytic Gene Expression by Biomechanical Signals

“…37 Furthermore, cyclic tensile strain could augment cartilage repair by facilitating the induction of ACAN mRNA and attenuation of IL-1β-induced suppression of PG synthesis (Fig. 2).…”

“…In chondrocytes, biomechanical signals are perceived in magnitude-and frequency-dependent manners to promote or attenuate proinflammatory gene transcription. 37 Biomechanical signals are transduced to cells by surface molecules such as β-integrins and focal adhesion kinases/protein-tyrosine 2 kinases). 41 The proinflammatory response exhibited by articular chondrocytes subjected to tensile strain of higher magnitudes is paralleled by an increase in NF-κB nuclear import, providing support for a central role of NF-κB in the proinflammatory signals generated by tensile loading.…”

“…38 Conversely, at lower magnitudes, biomechanical signals inhibit nuclear translocation of NF-κB transcription factors and act as potent inhibitors of IL-1β-and TNF-α-dependent proinflammatory gene transcription. 37,42,43 Multiple cytokine-induced proinflammatory pathways converge at the signalosome composed of inhibitor of κ light polypeptide gene enhancer in B cells kinase, IKKα (IKKA/ IKK1/conserved helix-loop-helix ubiquitous kinase); IKKβ (IKKB/IKK2/IKBKB); and IKKγ (NF-κB essential modifier/IKBKG) to activate downstream events in the NF-κB cascade. Upon phosphorylation by IKKs, inhibitor of κ light polypeptide gene enhancer in B cells protein, I-κB, is ubiquinated and marked for proteosomal degradation.…”