Trans-scale Simulation Study Of Mechano-signal Transduction Of Osteocytes

Bone is a kind of porous tissue full of fluid,the mass and structure of bone are always changing to adapt the continuous change of the mechanical environment.Osteocytes are important "mechanical sensors" in bone tissue,which can transmit mechanical signals and then regulate the activities of effector cells(such as osteoblasts and osteoclasts),thus regulating bone remodeling.Primary cilium and osteocyte processes are important functional units of osteocytes and play an important role in the mechanical signal transduction of osteocytes.This paper mainly studies the change rule of osteocyte mechanical signal transduction under microgravity field and the rule of the influence of low-intensity pulsed ultrasound(LIPUS)on osteocyte mechanical signal transduction.It is expected to reveal the mechanism of disuse osteoporosis in astronauts and mechanism of LIPUS in preventing and treating osteoporosis.The fluid solid coupling finite element model of single bone lacunae-osteocyte system(including homogenized osteocyte body,primary cilium,osteocyte process,canaliculi and tethering elements(TES))and a fluid-structure coupling finite element model for osteon with a two-stage pore structure(Haversian canal,lacunar-canalicular system)were established across scales.The numerical simulation was used to compare and study the changes of mechanical signal transduction of osteocytes(osteocyte body,primary cilium,osteocyte processes,etc.)under various gravity fields,and the influence of LIPUS stimulation on mechanical signal transduction of osteocytes.At the same time,the stress strain amplification mechanism of the coupling effect of TES and fluid in bone tubules was verified.The results show that:(1)Significant stress concentration was observed in the area of physical connection between TES and the osteocyte process,where the fluid shear stress(FSS)was around two orders of magnitude higher than that in other areas.FSS of osteocyte body,primary cilium and osteocyte processes increased linearly with the approximate range of G value.Because the TES structure has a significant amplification effect on mechanical stimulation,the osteocyte process has a stronger mechanical signal transduction capacity than the osteocyte body and primary cilium,making it the "best mechanical receptor".In addition,in microgravity,the ability of osteocytes to transmit mechanical signals was significantly reduced.(2)Dynamic loading can effectively increase von Mises stress of bone matrix and osteocytes,and the stress increases with the increase of loading frequency.In microgravity,the FSS of each mechanical receptor under the action of dynamic load with frequency of 2 Hz is 1.6-3 times that of the human body in the resting state.Therefore,high frequency antagonistic exercise can effectively improve the mechanical microenvironment of osteocytes,thus slowing down the disuse osteoporosis that occurs during space flight.(3)The von Mises stress of osteocytes under the action of LIPUS is positively correlated with the received sound pressure.Properly increasing the excitation sound pressure can effectively enhance the mechanical signal transmission capacity of osteocytes.(4)LIPUS irradiation can significantly increase the stress on the osteocyte body,primary cilium and osteocyte processes,thereby improving the mechanical microenvironment of osteocytes and enhancing their ability to transmit mechanical signals,so as to prevent and treat osteoporosis.The results of this study reveal the changing rule of the influence of external environment on the mechanical signal transduction of osteocytes,and provide theoretical guidance for clinical treatment of osteoporosis.