Abstract
Adolescent idiopathic scoliosis (AIS) is the most prevalent pediatric spinal deformity. We previously demonstrated elongated cilia and an altered molecular mechanosensory response in AIS osteoblasts. The purpose of this exploratory study was to characterize the mechanosensory defect occurring in AIS osteoblasts. We found that cilia length dynamics in response to flow significantly differ in AIS osteoblasts compared to control cells. In addition, strain-induced rearrangement of actin filaments was compromised resulting in a failure of AIS osteoblasts to position or elongate in function of the bidirectional-applied flow. Contrary to control osteoblasts, fluid flow had an inhibitory effect on AIS cell migration. Moreover, flow induced an increase in secreted VEGF-A and PGE2 in control but not AIS cells. Collectively our data demonstrated that in addition to the observed primary cilium defects, there are cytoskeletal abnormalities correlated to impaired mechanotransduction in AIS. Thus, we propose that the AIS etiology could be a result of generalized defects in cellular mechanotransduction given that an adolescent growing spine is under constant stimulation for growth and bone remodeling in response to applied mechanical forces. Recognition of an altered mechanotransduction as part of the AIS pathomechanism must be considered in the conception and development of more effective bracing treatments.