Abstract
ObjectivesOsteoblasts lay down new bone on implant surfaces. The underlying cellular mechanism and the spatio‐temporal mode of action, however, remain unclear. It can be proposed that growth factors released upon acidification by osteoclasts adsorb to the implant surface and control the early stages of osseointegration.MethodsTo simulate bone lysis by osteoclasts, titanium discs were exposed to acid bone lysate (ABL) followed by vigorous washing and seeding of oral fibroblasts. The expression of TGF‐β target genes interleukin 11 (IL11) and NADPH oxidase 4 (NOX4) was evaluated by reverse transcriptase polymerase chain reaction and IL11 ELISA. TGF‐β signaling activation was assessed via Smad2/3 immunofluorescence. The impact of ABL on osteogenic differentiation was determined with murine ST2 mesenchymal stromal cells.ResultsWe report here that ABL‐conditioned titanium discs, independent of turned or rough surface, increased the expression of IL11 and NOX4. This increase was blocked by the TGF‐β receptor 1 antagonist SB431542. Further support for the TGF‐β signaling activation came from the translocation of Smad2/3 into the nucleus of oral fibroblasts. Moreover, titanium discs exposed to ABL decreased alkaline phosphatase and osteopontin in ST2 cells.ConclusionsThese in vitro findings suggest that titanium can adsorb TGF‐β from ABLs. The data provide a strong impetus for studies on the protein adsorption on implant surfaces in vitro and in vivo, specifically for growth factors including bone‐derived TGF‐β during successful and failed osseointegration.
Highlights
Osseointegration of dental implants is a sequential process that is initiated by drilling the implant bed
We have previously reported on acid bone lysate (ABL) containing transforming growth factor beta (TGF-β)[15] refining knowledge from the 1980s
Cell viability was further confirmed by Live-Dead staining demonstrating most notably high living cells (Figure 1B). These findings indicate that cells seeded onto titanium discs coated with ABL are viable under the present in vitro model
Summary
Osseointegration of dental implants is a sequential process that is initiated by drilling the implant bed. Considering that the rapid loss of primary stability[14] is caused by bone-resorbing osteoclasts,[1,2] it is possible that bone-derived growth factors released by acidification adsorb to the implant surface, thereby causing a cellular response during early osseointegration. Since ABL prepared by the hydrochloric acid demineralization of bone chips activates TGF-β signaling[15] and that recombinant TGF-β1 adsorbs to titanium alloys[24] it was reasonable to suggest that bonederived TGF-β binds to the titanium surface triggering a TGF-β dependent cell response, thereby simulating the early stages of osseointegration
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