Effect of spinal cord injury on signaling pathways in mesenchymal stem cell-derived osteoblasts

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Objective To investigate the changes in Wnt/β-catenin, bone morphogenic protein (BMP), estrogen receptor (ER) and insulin-like growth factor (IGF) signaling pathways in bone marrow mesenchymal stem cells (BMSCs) differentiation to the osteoblasts after spinal cord injury (SCI) and understand the mechanism of osteoporosis after SCI. Methods Forty 6-week-old male rats were divided into SCI group (n=20) and control group (n=20) according to the random number table. Rats in SCI group were submitted to laminar osteotomy at T10-12 and given lower thoracic cord sharp transection. In control group, rat lower thoracic cord was only exposed without transaction. Femoral bone marrow density (BMD) of rat right side was determined at postoperative 3 months. Femoral bone marrow was harvested from rat left side. After BMSCs osteoblast differentiation, cells were harvested and used for examining expression of genes associated with the signaling pathways in the two groups using microarray technology and real-time PCR analysis. Results BMD in SCI group was significantly lower in the ephiphyses and metaphyses[(0.176±0.017)g/cm2 and (0.170±0.016)g/cm2] compared to that in control group [(0.257±0.023)g/cm2 and (0.196±0.013)g/cm2 , P<0.05]. Microarray and PCR analysis revealed Wnt/β-catenin (eg. Wnt1, Wnt3a, Wnt5a, Lrp5, Ctnnb1, Lef1 and Axin), BMP (Tgfb1 and Bmpr1), IGF-1 (eg. IGF1R, c-fos and c-Jun), and ER (eg. Esr1) signaling pathways in osteoblasts were significantly down-regulated in SCI group compared to these in control group (P<0.05). Conclusions The Wnt/β-catenin, BMP, ER, and IGF-1 signaling pathways in osteoblasts are significantly down-regulated after SCI, resulting in profound BMD loss. This indicates that these signaling pathways are implicated in the osteoporosis after SCI. Key words: Spinal cord injuries; Osteoporosis; Signal transduction; Osteoblast differentiation