mTOR signalling mediates the spinal osteoblast pathotype at the curve apex in adolescent idiopathic scoliosis

To investigate site-specific osteoblast phenotypes at the spinal curve apex, we performed bulk RNA sequencing on primary matched osteoblasts isolated from the convex, concave, and non-curved regions of AIS patients. Principal component analysis revealed distinct transcriptional clustering by spinal site, independent of patient-specific factors.

Differential expression analysis identified region_x0002_specific molecular profiles in convex and concave osteoblasts compared to non-curve controls, with the mTOR pathway being highlighted as one of the most dysregulated. Rapamycin, an mTOR inhibitor, reduced Alkaline phosphatase (ALP) activity, Osteoprotegerin (OPG) secretion, and mineralization, while modulating osteogenic gene expression, including sustained upregulation of RUNX2 and COL1A1.