The formation of osteolytic bone lesions is a key process for osteolytic cancer to metastasize to the bone and is under the control of a set of transcription factors. Recently, the inhibitor of differentiation 1 (Id1) has been linked with angiogenesis, tumorigenesis, metastasis and bone formation. However, the function of Id1 during the process of bone destruction caused by cancer in vivo has not yet been elucidated. We, therefore, examined whether and how Id1 affects the ability of cancer to form osteolytic lesion in vivo. The study used a lentiviral vector overexpressing short hairpin RNA (shRNA) targeting Id1 gene. PC3 cells, a prostate cancer cell line, were transduced with Id1 shRNA or negative control (NC) shRNA before implantation in BALB/c mice. Cells were implanted in a tibial injection model. Tumor formation in bone was monitored by X-ray. The relationship between parathyroid hormone-related protein (PTHrP), an osteolytic factor, and Id1 was analyzed by using immunohistochemistry in tissue sections from osteolytic lesion of the BALB/c mice. Our results showed that Id1 shRNA delivery to PC3 cells by lentivirus caused efficient and stable Id1 gene silencing. In the intratibial model, PC3 cells produced primarily osteolytic lesions in the bone. Eleven of 14 mice in Id1 shRNA group but only 4 of 14 mice in the NC shRNA group developed osteolytic lesions with cortical destruction at 4th week. Mice treated with Id1 shRNA had larger tumor volume in the bone and larger cortical destruction. The expression of PTHrP protein in PC3 cells was not affected by Id1 knockdown in vivo. These results indicate that Id1 may down-regulate the ability of PC3 cells to form osteolytic lesions in vivo and the signal pathway needs to be further investigated.

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The principal aim of present study was to assess the therapeutic e cacy of bone morphogenetic protein-7 (BMP-7) induced bone marrow mesenchymal stem cells (BMSCs) differentiation in rat acute spinal cord injury (SCI) model. BMSCs were isolated from rats, then divided into control and BMP7 induction groups.The proliferation ability of BMSCs and glial cell markers were detected. Forty Sprague-Dawley (SD) rats were randomly divided into sham, SCI, BMSCs, and BMP7 + BMSCs groups (n = 10). The recovery of motor function of hind limbs of rats, the pathological, related markers and motor evoked potentials (MEP) were detected. BMSCs differentiated into neuron like cells after exogenous BMP7 intervention. Interestingly, the expression levels of MAP-2 and Nestin increased, while the expression GFAP level decreased after exogenous BMP7 intervention. BBB score reached 19.33 ± 0.58 in the BMP7 + BMSCs group at day 42. Nissl bodies in model group were reduced compared to sham group. After 42 days, both in the BMSCs and BMP7 + BMSCs groups, the number of nissl bodies were increased. Especially, the number of nissl bodies in the BMP7 + BMSCs group was more than that in BMSCs group. The expression of Tuj-1 and MBP in BMP7 + BMSCs group increased, while the expression of GFAP decreased. MEP waveform decreased signi cantly after surgery. The waveform was wider, the amplitude was higher in BMP7 + BMSCs group than that in BMSCs group. BMP7 promotes BMSCs proliferation, and induces BMSCs differentiate into neuron like cells, inhibits the formation of glial scar. BMP7 plays a con dent role in the recovery of SCI rats.