Evidence of Intrinsic Impairment of Osteoblast Phenotype at the Curve Apex in Girls With Adolescent Idiopathic Scoliosis

Abstract

Study design: An observational descriptive study based on a single cohort of patients.

Objective: To determine whether spinal facet osteoblasts at the curve apex display a different phenotype to osteoblasts from outside the curve in adolescent idiopathic scoliosis (AIS) patients.

Summary of background data: Intrinsic differences in the phenotype of spinal facet bone tissue and in spinal osteoblasts have been implicated in the pathology of AIS. However, no study has compared the phenotype of facet osteoblasts at the curve apex compared with outside the curve in AIS patients.

Methods: Facet spinal tissue was collected perioperatively from three sites, the concave and convex side at the curve apex and from outside the curve (noncurve) from three AIS female patients aged 13-16 years. Spinal tissue was analyzed by micro-computed tomography to determine bone mineral density (BMD) and trabecular structure. Primary osteoblasts were cultured from concave, convex, and noncurve facet bone chips. The phenotype of osteoblasts was determined by assessment of cellular proliferation, cellular metabolism (alkaline phosphatase and Seahorse Analyzer), bone nodule mineralization (Alizarin red assay), and the mRNA expression of Wnt signaling genes (quantitative reverse transcriptase polymerase chain reaction).

Results: Convex facet tissue exhibited greater BMD and trabecular thickness, compared with concave facet tissue. Osteoblasts at the convex side of the curve apex exhibited a significantly higher proliferative and metabolic phenotype and a greater capacity to form mineralized bone nodules, compared with concave osteoblasts. mRNA expression of SKP2 was significantly greater in both concave and convex osteoblasts, compared with noncurve osteoblasts. The expression of SFRP1 was significantly downregulated in convex osteoblasts, compared with either concave or noncurve.

Conclusions: Intrinsic differences that affect osteoblast function are exhibited by spinal facet osteoblasts at the curve apex in AIS patients.

Level of evidence: Level IV, Prognostic.

Keywords: Adolescent idiopathic scoliosis; Bone; Curve apex; Osteoblasts; Wnt signalling.