The expression of matrix metalloproteinase-13 (MMP-13), involved in bone turnover, is elevated in stretched MC3T3-E1 osteoblast-like cells. Strain-mediated forces impact bone remodeling due in large part to the movement of fluid through the canalicular-lacunar network. The resulting fluid shear stress (FSS) over the surface membranes of bone cells initiates bone remodeling. Although the nuclear events mediating putative FSS-induced changes in osteoblast MMP-13 transcription are unknown, previous studies with bone cells suggest an overlap between osteoblast FSS- and PTH-induced signal response pathways. MMP-13 PTH response is regulated by a 110 bp 5' regulatory region, conserved across the mouse, rat, and human genes, that supports the binding of numerous transcription factors including Runx2, c-fos/c-jun, Ets-1, and nuclear matrix protein 4/cas interacting zinc finger protein (Nmp4/CIZ) a nucleocytoplasmic shuttling trans-acting protein that attenuates PTH-driven transcription. Nmp4/CIZ also binds p130(cas), an adaptor protein implicated in mechanotransduction. Here we sought to determine whether Nmp4/CIZ contributes to FSS-induced changes in MMP-13 transcription. FSS (12 dynes/cm(2), 3-5 h) increased MMP-13 promoter-reporter activity approximately two-fold in MC3T3-E1 osteoblast-like cells attended by a comparable increase in mRNA expression. This was accompanied by a decrease in Nmp4/CIZ binding to its cis-element within the PTH response region, the mutation of which abrogated the MMP-13 response to FSS. Interestingly, FSS enhanced Nmp4/CIZ promoter activity and induced p130(cas) nuclear translocation. We conclude that the PTH regulatory region of MMP-13 also contributes to FSS response and that Nmp4/CIZ plays similar but distinct roles in mediating hormone- and FSS-driven induction of MMP-13 in bone cells.

3D interconnected porous scaffolds of HA and HA with various additions of SiO2 were fabricated using a polymeric template technique, to make bioceramic scaffolds consisting of macrostructures of the interconnected macropores. Three different sizes of the polyurethane template were used in the fabrication process to form different size interconnected macropores, to study the effect of pore size on human osteoblast cell viability. The template used allowed fabrication of scaffolds with pore sizes of 45, 60, and 75 ppi, respectively. Scanning microscopy was used extensively to observe the microstructure of the sintered samples and the characteristics of cells growing on the HA surfaces of the interconnected macropores. It has been clearly demonstrated that the SiO2 addition has influenced both the phase transformation of HA to TCP (β-TCP and α-TCP) and also affected the human osteoblast cell viability grown on these scaffolds.