Effect of ErhBMP-2-loaded ß-tricalcium phosphate on ulna defects in the osteoporosis rabbit model.

PURPOSE: Autografts, the gold standard treatment for large bone defects, present complications, especially in conditions with reduced bone-repair capacity, such as osteoporosis. Escherichia coli-derived recombinant human bone morphogenesis protein-2 (ErhBMP-2), was used in this study to improve the osteoinductivity of ß-tricalcium phosphate (ß-TCP). This study evaluated the bone-repair capacity of ErhBMP-2-loaded ß-TCP on osteoporosis rabbit model, relative to the sole use of autograft and ß-TCP treatments. METHODS: The osteoporosis rabbit model was induced through ovariectomy and glucocorticoid dosing; 2-cm segmental ulnar defects were created, which were treated with either autograft, ß-TCP alone, or ErhBMP-2-loaded ß-TCP or left untreated. The quality of newly formed ulnae was evaluated 8 weeks after ulnar surgery through micro-CT, biomechanical, histological, and histomorphometric assessments. RESULTS: The osteoporosis rabbit model was developed and maintained till the end of the study. The maximal load and stiffness in the ErhBMP-2-loaded TCP group were significantly higher than those in the autograft group, whereas the TCP-alone group performed similarly as did the untreated group in the force loading and stiffness tests. According to the micro-CT evaluation, the ErhBMP-2-loaded TCP group had significantly higher bone volume relative to the autograft and TCP-alone groups. Histological assessments revealed better defect bridging and marrow formation in the ErhBMP-2-loaded TCP group relative to the TCP-alone group. Mineral apposition rates were significantly higher in the ErhBMP-2-loaded TCP and autograft groups than in the TCP-alone and untreated groups. CONCLUSION: Relative to autografts, ErhBMP-2-loaded TCP, as an alternative grafting material, provides better or comparable healing on critical-sized long bone defects in the osteoporosis rabbit model.

Insulin-like growth factor binding Protein-3 suppresses osteoblast differentiation via bone morphogenetic protein-2.

Bone augmentation therapy is used in dental implantation. While techniques to induce bone formation are generally successful, the maintenance of bone mass is more difficult. Therefore, it is important to understand the mechanisms that regulate this process. Insulin-like growth factor-1 (IGF-1) is one of the most abundant growth factors that regulate bone mass, promote osteoblast differentiation, and accelerate bone formation. The activity of IGF-1 is regulated by IGF-binding proteins (IGFBPs). IGFBP-3 forms a ternary complex with IGF-1, extending its half-life in the circulating system. Therefore, IGFBP-3 acts as a stabilizer and transporter of IGF-1. Recent studies reported new IGF-1-independent functions of IGFBP-3 related with bone metabolism. In this study, we investigated the function of IGFBP-3 in osteoblast differentiation. Our results showed that IGFBP-3 decreases the expression of osteoblast differentiation markers, whose expression is enhanced by bone morphogenetic protein-2 (BMP-2). IGFBP-3 also reduced BMP-2 effect on ALP activity and mineral nodule formation. In addition, IGFBP-3 suppresses the activity of the Smad Binding Element (SBE) reporter, induced by BMP-2 signaling. These results suggest that IGFBP-3 inhibits osteoblast differentiation through the BMP-2 signal pathway, and that IGFBP-3 might play a role in bone mass maintenance in an IGF-1-dependent and -independent manner.

The Bone Morphogenesis Protein-2 (BMP-2) is associated with progression to metastatic disease in gastric cancer.

PURPOSE: Bone Morphogenetic Proteins (BMPs) are members of the TGF-beta superfamily and it has been demonstrated that BMPs enhance migration, invasion and metastasis. The purpose of this study was to identify the association between the serum BMP-2 level and the progression status of gastric cancer. MATERIALS AND METHODS: Fifty-five patients with metastatic gastric cancer (metastatic disease group), six patients with early gastric cancer without lymph node metastasis (the EGC group), and ten healthy control subjects were enrolled in this study. The serum BMP-2 level was quantified by use of a commercially available ELISA kit. In EGC group patients and patients with metastatic disease, whole blood was obtained before endoscopic mucosal resection and before the commencement of a scheduled cycle of systemic chemotherapy, respectively. RESULTS: No significant difference in the mean serum BMP-2 levels was observed between the control subjects and the EGC group patients (87.95 pg/ml for the control subjects and 84.50 pg/ml for the EGC group, p=1.0). However, the metastatic disease group patients had a significantly higher level of serum BMP (179.61 pg/ml) than the control subjects and EGC group patients (87.95 pg/ml for the control subjects and 84.50 pg/ml for the EGC group, p<0.0001). Moreover, the mean serum BMP-2 level from patients with a bone metastasis was significantly higher than the mean serum BMP-2 level from patients without a bone metastasis (204.73 pg/ml versus 173.33 pg/ml, p=0.021). CONCLUSIONS: BMP-2 seems to have a role in progression to metastatic disease in gastric cancer, especially in the late stage of tumorigenesis, including invasion and metastasis. BMP-2 may facilitate bone metastasis in gastric cancer. To confirm these findings, further studies are required with tissue specimens and the use of a cancer cell line.

The Bone Morphogenesis Protein-2 (BMP-2) is Associated with Progression to Metastatic Disease in Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Bone Morphogenetic Proteins (BMPs) are members of the TGF-beta superfamily and it has been demonstrated that BMPs enhance migration, invasion and metastasis. The purpose of this study was to identify the association between the serum BMP-2 level and the progression status of gastric cancer. MATERIALS AND METHODS: Fifty-five patients with metastatic gastric cancer (metastatic disease group), six patients with early gastric cancer without lymph node metastasis (the EGC group), and ten healthy control subjects were enrolled in this study. The serum BMP-2 level was quantified by use of a commercially available ELISA kit. In EGC group patients and patients with metastatic disease, whole blood was obtained before endoscopic mucosal resection and before the commencement of a scheduled cycle of systemic chemotherapy, respectively. RESULTS: No significant difference in the mean serum BMP-2 levels was observed between the control subjects and the EGC group patients (87.95 pg/ml for the control subjects and 84.50 pg/ml for the EGC group, p=1.0). However, the metastatic disease group patients had a significantly higher level of serum BMP (179.61 pg/ml) than the control subjects and EGC group patients (87.95 pg/ml for the control subjects and 84.50 pg/ml for the EGC group, p<0.0001). Moreover, the mean serum BMP-2 level from patients with a bone metastasis was significantly higher than the mean serum BMP-2 level from patients without a bone metastasis (204.73 pg/ml versus 173.33 pg/ml, p=0.021). CONCLUSIONS: BMP-2 seems to have a role in progression to metastatic disease in gastric cancer, especially in the late stage of tumorigenesis, including invasion and metastasis. BMP-2 may facilitate bone metastasis in gastric cancer. To confirm these findings, further studies are required with tissue specimens and the use of a cancer cell line.

Effects of different oxygen concentrations on differentiation of marrow stroma cells into osteoblasts / 中国病理生理杂志

AIM:To investigate the effect of different oxygen concentrations on the differentiation of marrow stroma cells into osteoblasts and to evaluate the expression of Cbf?1 /Runx2,bone-morphogenesis protein 2 (BMP2) and peroxisome proliferator-activated receptor ?2 (PPAR-?2) in bone marrow stromal cells. METHODS:The bone marrow stomal cells obtained from 4-month-old female SD rats were cultured in growth medium and were used between passages 3 to 5. The cells were divided randomly into 4 groups,each group has 8 samples. The cells in all 4 groups were used for the following experiments after cultured with different oxygen concentrations for 3 d in osteoblastic differentiation medium:total cellular RNA was isolated using total RNA kit; RT -PCR was performed to detect the mRNA expression of Cbf?1 /Runx2,BMP2 and PPAR?2. The protein expression of Cbf?1 /Runx2 and BMP2 was assayed by Western blotting. RESULTS:Compared to the cells in normoxia condition (20% ),the mRNA and protein expressions of Runx2 were enhanced significantly,the mRNA expression of BMP2 was also enhanced significantly,the protein expression of BMP2 increased and the mRNA expression of PPAR?2 decreased significantly in the cells cultured with lower oxygen concentrations. The lower oxygen con-centration was in the culture,the more Runx2 mRNA,BMP2 mRNA,BMP2 and Runx2 protein were expressed. On the contrary,hypoxia significantly decreased the expression of PPAR?2 mRNA in bone marrow stronmal cells and the lower the oxy-gen concentration was used,the less expression of PPAR?2 mRNA was achieved. CONCLUSION:Hypoxia promotes the mRNA and protein expressions of Runx2 and BMP2,also significantly decreases the expression of PPAR?2 mRNA in bone marrow stronmal cells in an oxygen concentration dependent manner,indicating that hypoxia significantly stimulates the differentiation of bone marrow stromal cells into osteoblasts instead of lipocytes.