Matrix metalloproteinases MMP‐2, ‐9 and tissue inhibitors TIMP‐1, ‐2 expression and secretion by primary human osteoblast cells in response to titanium, zirconia, and alumina ceramics

Abstract

Osteogenic properties of bone cells are a key parameter governing osseointegration of implant devices. In this context, osteoblasts have a central role via extracellular matrix synthesis and remodeling that they regulate through different protease activity. In this study, we have analyzed the expression of two matrix metalloproteinases (MMPs): MMP-2 (72 kDa) and MMP-9 (92 kDa) and their specific tissue inhibitors TIMP-1 and TIMP-2 in primary human osteoblastic cells. The effect of titanium, zirconia, and alumina ceramics on the synthesis of these proteases was assessed using reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and zymographic analysis. Our results showed that osteoblasts express MMP-2 and -9 mRNA. Furthermore, MMP-2 mRNA expression was decreased by titanium and increased by alumina whereas zirconia did not have any significant effect. Conversely, MMP-9 mRNA expression was stimulated by titanium but decreased with zirconia, whereas alumina induced no significant changes. Zymographic analysis has evidenced pro-MMP-2 gelatinolytic activity in all cell populations with time-dependent increase profile; pro-MMP-9, however, was not detected. Enzyme-linked immunosorbent assay data confirmed the production of MMP-2 and very low levels of MMP-9. In addition, TIMP-1 was secreted in 24-hcultured cells and increased to maximal level at 48 -72 h whereas TIMP-2 levels were very low. The interactions between human osteoblasts and the studied biomaterials altered both MMP-2, -9 and TIMP-1expression indicating that biomaterials may influence osseointegration and bone remodeling.

Upregulation of matrix metalloproteinase (MMP)‐1 and its activator MMP‐3 of human osteoblast by uniaxial cyclic stimulation

“…Extracellular matrix degrading MMPs, secreted by osteoblasts, have been reported to be involved in physiologic and pathological bone remodeling. MMP‐1, ‐2, ‐3, and ‐13 have been suggested to play a role in physiologic bone remodeling,8, 9, 12 MMP‐13 in fracture healing22, and MMP‐2 and MMP‐9 in foreign body reaction relating to periprosthetic osteolysis 23, 24. This study showed that uniaxial cyclic stretching transiently upregulated the expression of MMP‐1 and MMP‐3 in normal human osteoblasts cultured on collagen gels.…”

Acute and long-term in vitro effects of zinc oxide nanoparticles

“…Besides, we found that there was no significant secretion of MMP2 and 9 in both cell lines and time intervals due to ZnO NP and ZnCl 2 treatments. It was considered that MMPs as zinc-dependent endopeptidases play crucial roles in tumor invasion, morphogenesis, angiogenesis, metastasis, and wound healing by remodelling of extracellular matrix (Murphy et al 1994;Parsons et al 1997;Oum'hamed et al 2004). These data suggested lack of early acquisition of cancer markers upon ZnO NP and ZnCl 2 chronic exposures after chronic exposures despite the fact that vulnerable MEF Ogg1 gene knockout cell line was used.…”

The surface characterization and bioactivity of NANOZR in vitro

“…Boyan et al 46) demonstrated that rough surface may enhance osteoblasts differentiation, and fine-tuning of the biomaterial surface topography may also possible control intracellular signaling events 47) . Oum'hamed et al 48) and Carinci et al 10) showed in their studies that zirconia, alumina, and titanium are able to upregulate or downregulate the expression of some genes and proteinases. We presume that the higher ALP expression of NANOZR maybe ascribes to its unique intergranular-type nanostructure, and ceria and alumina in NANOZR may also affect the osteoblast differentiation.…”