Uptake of nickel from 316L stainless steel into contacting osteoblastic cells and metal ion interference with BMP‐2‐induced alkaline phosphatase

Abstract

Bone cells contacting nickel (Ni)-containing implant materials may be affected by Ni species via disturbed signaling pathways involved in bone cell development. Here we analyze effects of the Ni-containing steel 316L and major metal constituents thereof on bone morphogenetic protein-2 (BMP-2)-induced alkaline phosphatase (ALP) of MC3T3-E1 cells. While cells grew normally on 316L, cellular Ni content increased 10-fold vs. control within 4 days. With respect to the major components of 316L, Ni2+ (3-50 microM) was most inhibitory to BMP-2-induced ALP, whereas even 50 microM Fe3+, Cr3+, Mo5+, or Mn2+ had no such effect. In line with this, BMP-2-induced ALP was significantly reduced in cells on 316L. This effect was not prevented by the metal ion chelator diethylenetriaminepentaacetic acid (DTPA). Instead, DTPA abolished the stimulatory effect of BMP-2 on ALP, pointing to chelatable metal ions involved. Zn2+, as one possible candidate, antagonized the Ni2+ inhibition of BMP-2-induced ALP in both MC3T3-E1 and human bone marrow stromal cells. Results show that cells contacting 316L steel are exposed to increased concentrations of Ni which suffice to impair BMP-2-induced ALP activity. Zn2+, as a competitor of this inhibition, may help to restore normal osteoblastic function and bone development under these conditions.

Concentration‐dependent cellular behavior and osteogenic differentiation effect induced in bone marrow mesenchymal stem cells treated with magnetic graphene oxide

“…BMP‐2 is an important molecule involved in bone formation, which induces transcription factors such as Runx2. The BMP signaling pathway also plays a role in osteoblast differentiation, as well as the synthesis and secretion of the extracellular matrix (Meng et al, ; Molders, Felix, Bingmann, Hirner, & Wiemann, ). In our present study, at both gene and protein levels, we discovered that MGO nanoparticles could promote BMP‐2 expression, which in turn accelerated Runx2 expression.…”

The progress on physicochemical properties and biocompatibility of tantalum-based metal bone implants

“…Co(II) can significantly reduce the movement ability of macrophages and inhibit cell migration by RhoA downregulation and cytoskeleton reorganization, which is still happened by the emergence of ROS [57]. Ni ions gradually accumulated in cells also affect the ability of bone morphogenetic protein (BMP-2) to induce alkaline phosphatase (ALP) formation [58,59]. Some studies have shown that compared with Nitinol, the surface layer rich in Ti or Ta can significantly reduce the formation of ROS and longevity protein free radicals [60].…”

R.T.R^® promotes bone marrow mesenchymal stem cells osteogenic differentiation by upregulating BMPs/SMAD induced <i>cbfa1</i> expression

“…It is not clear the molecular mechanism of BMP-1 differentially expressed in BMSCs grown on Bio-Oss ® and R.T.R ® . It is possible that the difference of BMP-1 expression level caused by the difference of zinc ion content in the two materials may lead to the obvious difference of BMSCs differentiating into osteoblasts 32) .…”