Reduced mineralization potential of osteoblasts in adolescent idiopathic scoliosis: intrinsic dysfunction and crosstalk with TLR-activated chondrocytes

Background Patients with Adolescent Idiopathic Scoliosis (AIS) present with facet joint osteoarthritis, which may contribute to curve progression. While inflammatory mediators from degenerative cartilage are known to influence osteoclast activity, their effects on osteoblast function in AIS remain unclear. Methods Primary facet joint osteoblasts were isolated from AIS patients undergoing spinal fusion surgery and age-matched non-scoliotic (NSC) individuals from organ donors. Transcriptomic profiles were generated by RNA sequencing, and key regulatory pathways were identified through bioinformatic analysis. Selected genes of interest were validated in an expanded cohort by qPCR. Functional capacity was assessed by comparing mineralization between AIS and NSC osteoblasts in a hydroxyapatite–collagen (HA–Col) three-dimensional culture system. The influence of Toll-Like Receptor (TLR) 2- or 4-pre-activated chondrocytes on osteoblast function was evaluated through qPCR analysis of bone-associated genes and mineralization assays. Results AIS osteoblasts displayed 1,357 differentially expressed genes (635 upregulated, 722 downregulated) with enrichment of inflammatory pathways in Gene Ontology analysis and negative enrichment of bone-related gene sets in gene set enrichment analysis. Key osteogenic markers, including SP7, ALP, and COL1A1, were downregulated by RNA sequencing and confirmed by qPCR. Mineralization capacity was significantly impaired in AIS osteoblasts. Conditioned media from TLR2- or TLR4-pre-activated chondrocytes induced IL-6 expression, reduced osteocalcin levels, and further decreased osteoblast mineralization capacity. Conclusions AIS facet joint osteoblasts exhibit intrinsic mineralization deficits, which are exacerbated by inflammatory mediators released from TLR-activated chondrocytes. These findings identify TLR-mediated cartilage–bone signalling as a potential therapeutic target to preserve facet joint integrity and maintain subchondral bone remodelling in AIS.