Regulation of Chondrocytic Gene Expression by Biomechanical Signals

Abstract

Cartilage is a mechanosensitive tissue, which can means that it can perceive and respond to biomechnical signals. Despite the known importance of biomechanical signals in the etiopathogenesis of arthritic diseases, and their effectiveness in joint restoration, little is understood about their actions at the cellular level. Recent molecular approaches have revealed that specific biomechanical stimuli and cell interactions generate intracellular signals that are powerful inducers or suppressors of proinflammatory and reparative genes in chondrocytes. Biomechanical signals are perceived by cartilage in magnitude-, frequency-, and time-dependent manners. Static and dynamic biomechanical forces of high magnitudes induce proinflammatory genes and inhibit matrix synthesis. Contrarily, dynamic biomechanical signals of low/physiologic magnitudes are potent antiinflammatory signals that inhibit interleukin-1β (IL-1β)-induced proinflammatory gene transcription and abrogate IL-1β/tumor necrosis factor-α-induced inhibition of matrix synthesis. Recent studies have identified nuclear factor-κB (NF-κB) transcription factors as key regulators of biomechanical signal-mediated proinflammatory and antiinflammatory actions. These signals intercept multiple steps in the NF-κB signaling cascade to regulate cytokine gene expression. Taken together, these findings provide insight into how biomechanical signals regulate inflammatory and reparative gene transcription, underscoring their potential in enhancing the ability of chondrocytes to curb inflammation in diseased joints.

Effects of exercise on physical limitations and fatigue in rheumatic diseases

“…The key intervention in the management of OA is exercise therapy [37,38] . It is well known that exercise training affects the articular cartilage metabolism and modifies the cartilaginous structure by a mechanotransduction response [37][38][39] . Biomechanical stimulus generated by dynamic compression, during a moderate exercise, can reduce the synthesis of proteolytic enzymes, regulating the metabolic balance and preventing the progression of the disease [40,41] .…”

Anti-Inflammatory Strategies in Cartilage Repair

“…90 A high-magnitude mechanical strain is proinflammatory and initiates cartilage destruction while inhibiting matrix synthesis, both of which are involved in the NF-kB-related signal pathway. 91,92 It has been reported that a low-magnitude mechanical strain inhibits inflammation by suppressing IL-1b and TNFa-induced transcription of multiple proinflammatory mediators involved in cartilage degradation. 91 It is noteworthy, however, that the influences of mechanical stress are not independent; many mechanical and physiochemical factors that are known to affect chondrocytes are inextricably coupled to one another within the cartilage ECM.…”

Information as a Manifestation of Development

“…For example, many tissues are composed of epithelia wherein the cells are polarized along an apical-basal axis defined by the basal location of a collagen-containing extracellular matrix, and linked together with intercellular junctions, thus forming an integrated unit. Mechanical forces (e.g., stretching) experienced by the tissue-and hence by the cells within the tissue-influence the regulatory state within nucleus of each cell by activating latent regulatory proteins [36][37][38]. Finally, the fully formed organism provides systemic hormonal cues that affect the regulatory states of nuclei throughout the body or within specific organs in response to environmental cues (e.g., diet, pheromones, light, temperature etc.…”