Abstract

Osteocytes sense mechanical forces in the extracellular environment, and regulate bone repair and regeneration by converting mechanical stimuli into biochemical signals. However, the underlying mechanism by which osteocytes orchestrate bone formation under conditions of mechanical force remains unclear. This research tested the hypothesis that transcriptional co-activator with PDZ-binding motif plays a key role in regulating osteocyte secretion factors receptor activator of nuclear factor-kappa b ligand and osteoprotegerin under conditions of mechanical stretching. To evaluate how transcriptional co-activator with PDZ-binding motif affected osteocyte secretion, we applied mechanical stretching force to MLO-Y4 cells. Pathway-related specific genes and proteins were evaluated using reverse transcription-polymerase chain reaction, Western blot and immunofluorescence. An enzyme-linked immunoassay was used to detect the secretion of soluble receptor activator of nuclear factor-kappa b ligand and osteoprotegerin. Mechanically induced transcriptional co-activator with PDZ-binding motif nuclear translocations promoted the release of osteoprotegerin and inhibited the expression and secretion of receptor activator of nuclear factor-kappa b ligand in osteocytes. Mechanical stretch forces signal resulting transcriptional co-activator with PDZ-binding motif mediated receptor activator of nuclear factor-kappa b ligand and osteoprotegerin expression and secretion. These results imply that transcriptional co-activator with PDZbinding motif may represent a therapeutic target for bone defect restoration.