Postnatal Expression of Pax1 in the Intervertebral Disc during Postnatal Growth and Response to Spinal Curvature

Abstract

Intervertebral discs (IVD) are fibrocartilaginous tissues of the spine that provide flexibility and absorb mechanical stress. Adolescent Idiopathic Scoliosis (AIS) is a multifactorial disease that causes sudden lateral curvature of the spine during the adolescent growth spurt but has no known cause. SNPs near the PAX1 gene have been associated with AIS patients, and PAX1 is known to be a key transcription activator in the embryonic development of the disc. However, the postnatal expression and function of PAX1 have not been addressed previously. In addition, Pax1-null mice develop spinal curvature, yet it is unclear how the mutation affects the disc to initiate or contribute to progression of the curve. This study provides the first detailed analysis of postnatal Pax1 expression in the mouse disc. Pax1 is found to be expressed in the NP and AF of lumbar and tail discs from neonatal to adult ages. Next, to study the effect of spinal curvature on Pax1, the tail looping method was applied to 6- and 8-week old mice for 1 and 4 weeks. Pax1 expression was maintained in the NP, but was reduced on the convex OAF and increased in the concave OAF. This indicates that Pax1 expression can be influenced by mechanical forces in postnatal growth and maintenance. Thus, PAX1 as a genetic risk factor may contribute to initiation and progression of spinal curvature in AIS from asymmetrical loading of the IVD. Studies of IVD development and curvature in Pax1-null mice are in progress, and genetic interaction with another transcription factor, Runx3 will be examined in the future.