Abstract: Objective To investigate the expression pattern of platelet-derived growth factor receptor alpha (PDGFRA) in bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) from patients with adolescent idiopathic scoliosis (AIS), and to evaluate its effects on osteogenic differentiation and proliferation of BM-MSCs. Methods Previously generated BM-MSC transcriptomic sequencing data from an established cohort were analyzed to identify differentially expressed genes (AIS, n=12; controls, n=5), and the findings were validated by qRT-PCR(AIS, n=12; controls, n=9). PDGFRA was knocked down by siRNA in normal BM-MSCs. After osteogenic induction, osteogenesis-related parameters were assessed by ALP staining/activity assay, Alizarin Red S staining, qRT-PCR, and Western blot. Cell proliferation was evaluated using CCK-8 assays. Results Compared with healthy controls, PDGFRA was significantly downregulated in BM-MSCs from patients with AIS. During the early stage of osteogenic induction, PDGFRA expression increased significantly on day 6 in healthy BM-MSCs. PDGFRA knockdown suppressed both early osteogenic activity and late mineralization in BM-MSCs, and reduced the expression of osteogenesis-related markers, including RUNX2, ALP, OPN, COL1A1, OSX, and IBSP. In addition, PDGFRA knockdown impaired the proliferation capacity of BM-MSCs. Conclusions PDGFRA is involved in the proliferation and osteogenic differentiation of BM-MSCs from healthy participants. Reduced PDGFRA expression in AIS BM-MSCs may contribute to impaired osteogenesis and low bone mass in AIS.

Key words: adolescent idiopathic scoliosis, bone marrow-derived mesenchymal stem cells, PDGFRA, osteogenic differentiation