Cadmium can cause apoptosis of mesenchymal progenitors and inhibit chondrogenesis.
Effects of sub-toxic Cadmium concentrations on bone gene expression program: results of an in vitro study.
"Exposure to the heavy metal Cadmium (Cd) affects human health. This study investigated the effects of exposure to a single, or multiple, sub-toxic Cd concentrations on sub-confluent and confluent human osteoblast growth. RT-PCR quantified gene expression of type I collagen, metalloprotease (MMP13), runt-related transcription factor-2 (RUNX2), osterix, osteocalcin, osteonectin, alkaline phosphatase, integrins and bone sialoprotein (BSP). Expression of fibroblast growth factors 1 and 2 (FGF1, FGF2), transforming growth factor-beta(3) (TGFbeta(3)) and bone morphogenetic protein-2 (BMP2) were also evaluated to determine whether Cd-related effects were mediated by an imbalance in expression. Depending on osteoblast concentration and maturation stages, Cd inhibited or stimulated cell growth, decreased type I collagen, increased MMP13, FGF1 and BMP2{BMP2 and MMP13 genes can affect height} gene expression and stimulated the mineralization process only in continuously exposed cultures. In vivo, acute or chronic exposure to sub-toxic Cd concentrations may affect bone formation differently and support the hypothesis that Cd-induced bone disorders may involve downstream changes in growth factor expression."
The osteoblasts were all from old individuals(50+).
"On day 22, untreated and Cd-treated osteoblasts, cultured according to protocol B, grew uniform confluent sheets of fibroblast-like and cubical cells, with nodular structures. These were apparently the result of coalescing aggregates under the inverted microscope"<-fibroblast cells can be precursors to chondrocyte cells.
"protocol B cultures were maintained in vitro for 22 days and exposed to Cd for the last 3 days"
Protocol B reduced type I collagen, Runx2, BSP, and osterix expression while increasing MMP13 expression so it was the most chondrogenic. The less chondrogenic protocols involved adding cadmium earlier or continuously adding cadmium to the medium.
However, Protocol B also decreased the expression of the pro-chondrogenic genes BMP-2 and TGF-Beta3. Only continuous administration of Cadmium increased BMP-2 levels.
" Cd had an inhibitory effect on cell number when added to a low density cellular sheet, while 0.1 μM Cd-stimulated cell number in 12-day sub-confluent and in 22-day confluent cultures."<-Higher density cells are more chondrogenic.
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