Noise differentially affects the osteocyte and osteoblast response to fluid shear stress

Stochastic resonance occurs in non-linear systems when the response to a weak periodic input is strengthened by the presence of noise. Whether a noisy mechanical environment can similarly increase the mechanosensitivity of bone cells, thereby amplifying their response to loading, remains unclear. Both osteocytes and osteoblasts react to fluid flow generated by mechanical loading, although osteocytes are considered the primary mechanosensors in bone. Therefore, the aim of this study was to investigate whether different noise intensities can enhance the mechanosensitivity of MLO-Y4 osteocytes compared with MC3T3-E1 osteoblasts. Bone cell activation was assessed by measuring nitric oxide (NO) and prostaglandin E₂ (PGE₂) production. The in vitro responses of MLO-Y4 osteocytes and MC3T3-E1 osteoblasts to noisy fluid shear stress were modeled by evaluating the increase in information content of the applied mechanical signal. Our findings showed that noise significantly amplified the NO response of MLO-Y4 osteocytes to a low-amplitude periodic fluid shear stress. In contrast, MC3T3-E1 osteoblasts did not exhibit a noise-enhanced NO response. However, osteoblasts demonstrated an increased PGE₂ response in the presence of noise, whereas osteocytes did not show a similar enhancement compared to noise-only stimulation. In conclusion, these distinct responses to noisy fluid shear stress suggest that MLO-Y4 osteocytes and MC3T3-E1 osteoblasts have different local bone adaptation implications for NO and PGE₂ production. Since both NO and PGE₂ are key regulators of bone formation and resorption, these results provide insight into how noise may promote osteocyte and osteoblast activity in vivo and contribute to mechanical adaptation of bone.