Control of osteoblast arrangement by osteocyte mechanoresponse through prostaglandin E2 signaling under oscillatory fluid flow stimuli.

Anisotropic collagen/apatite microstructure is a prominent determinant of bone tissue functionalization; in particular, bone matrix modulates its anisotropic microstructure depending on the surrounding mechanical condition. Although mechanotransduction in bones is governed by osteocyte function, the precise mechanisms linking mechanical stimuli and anisotropic formation of collagen/apatite microstructure are poorly understood. Here we developed a novel anisotropic mechano-coculture system which enables the understanding of the biological mechanisms regulating the oriented bone matrix formation, which is constructed by aligned osteoblasts. The developed model provides bone-mimetic coculture platform that enables simultaneous control of mechanical condition and osteoblast-osteocyte communication with an anisotropic culture scaffold. The engineered coculture device helps in understanding the relationship between osteocyte mechanoresponses and osteoblast arrangement, which is a significant contributor to anisotropic organization of bone tissue. Our study showed that osteocyte responses to oscillatory flow stimuli regulated osteoblast arrangement through soluble molecular interactions. Importantly, we found that prostaglandin E2 is a novel determinant for oriented collagen/apatite organization of bone matrix, through controlling osteoblast arrangement.