Mechanical properties of α-tricalcium phosphate-based bone cements incorporating regenerative biomaterials for filling bone defects exposed to low mechanical loads

Calcium phosphate-based cements with enhanced regenerative potential are promising biomaterials for the healing of bone defects. With a view to the use of such cements for low load bearing applications such as sinus augmentation or filling extraction sites, we have prepared α-tricalcium phosphate (α-TCP)-based bone cements including materials that we would expect to improve their regenerative potential, and describe the mechanical properities of the resulting formulations herein. Formulations incorporated α-TCP, hydroxyapatite, biopolymer-thickened wetting agents, sutures, and platelet poor plasma. The mechanical properties of the composites were composition dependent, and optimized formulations had clinically relevant mechanical properties. Such calcium phosphate-based cements have potential as replacements for cements such as those based on polymethylmethacrylate (PMMA)

Growth Factor-Independent 1 Is a Tumor Suppressor Gene in Colorectal Cancer

Colorectal cancer is the third most common cancer and the third leading cause of cancer death in the United States. Growth factor-independent 1 (GFI1) is a zinc finger transcriptional repressor responsible for controlling secretory cell differentiation in the small intestine and colon. GFI1 plays a significant role in the development of human malignancies, including leukemia, lung cancer, and prostate cancer. However, the role of GFI1 in colorectal cancer progression is largely unknown. Our results demonstrate that RNA and protein expression of GFI1 are reduced in advanced-stage nonmucinous colorectal cancer. Subcutaneous tumor xenograft models demonstrated that the reexpression of GFI1 in 4 different human colorectal cancer cell lines inhibits tumor growth. To further investigate the role of Gfi1 in colorectal tumorigenesis, we developed transgenic mice harboring a deletion of Gfi1 in the colon driven by CDX2-cre (Gfi1 ; CDX2-cre) and crossed them with Apc mice (Apc ; Gfi1 ; CDX2-cre). Loss of Gfi1 significantly increased the total number of colorectal adenomas compared with littermate controls with an APC mutation alone. Furthermore, we found that compound (Apc ; Gfi1 ; CDX2-cre) mice develop larger adenomas, invasive carcinoma, as well as hyperplastic lesions expressing the neuroendocrine marker chromogranin A, a feature that has not been previously described in APC-mutant tumors in mice. Collectively, these results demonstrate that acts as a tumor suppressor gene in colorectal cancer, where deficiency of Gfi1 promotes malignancy in the colon. IMPLICATIONS: These findings reveal that GFI1 functions as a tumor suppressor gene in colorectal tumorigenesis

Analysis of 1,25-dihydroxyvitamin D3 genomic action reveals calcium regulating and calcium independent effects in mouse intestine and human enteroids.

Although vitamin D is critical for the function of the intestine, most studies have focused on the duodenum. We show that transgenic expression of the vitamin D receptor (VDR) only in the distal intestine of VDR null mice (KO/TG mice) results in the normalization of serum calcium and rescue of rickets. Although it had been suggested that calcium transport in the distal intestine involves a paracellular process, we found that the 1,25(OH)2D3 activated genes in the proximal intestine associated with active calcium transport (Trpv6, S100g, Atp2b1) are also induced by 1,25(OH)2D3 in the distal intestine of KO/TG mice. In addition, Slc30a10, a manganese efflux transporter, was one of the genes most induced by 1,25(OH)2D3 in both proximal and distal intestine. Both villus and crypt were found to express Vdr and VDR target genes. RNA-seq analysis of human enteroids indicated that the effects of 1,25(OH)2D3 observed in mice are conserved in humans. Using Slc30a10-/- mice, a loss of cortical bone and a marked decrease in S100g and Trpv6 in the intestine was observed. Our findings suggest an interrelationship between vitamin D and intestinal Mn efflux and indicate the importance of distal intestinal segments to vitamin D action.status: Published onlin