Low expression of PDGFRA in bone marrow mesenchymal stem cells from patients with adolescent idiopathic scoliosis and its effects on osteogenic differentiation and proliferation

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.