The Role of MicroRNAs in the Osseointegration Process.

Regulation of cellular function is key to bone formation at endosseous implant surfaces. Osseointegration was "discovered" prior to the discovery of genetic regulation of osteoinduction or characterization of mesenchymal stem cells. Understanding osseointegration in cellular and molecular terms has benefited from genome-wide characterization of this healing process at endosseous implants in vivo. These in vivo studies also demonstrate a role for osteoprogenitor cells and cells involved in immune regulation and osteoclastogenesis. The identification of noncoding RNAs, including microRNAs, as key factors controlling cell function has highlighted the role of microRNAs in cell differentiation control. This review summarizes emerging in vitro and in vivo investigations emphasizing the role of microRNAs in the osseointegration process. Many microRNAs influence key osteoinductive pathways controlling Osterix, runt-related transcription factor 2 (RUNX2), and bone morphogenetic protein (BMP)/SMAD function. Others influence the monocyte/macrophage lineage. While significant progress has been made in elucidating the mechanisms associated with the regulation of surface modulation of osteoblast differentiation by microRNAs, knowledge gaps are evident in the identification and characterization of microRNAs linked to osseointegration. Given existing knowledge regarding the varied expression of microRNAs and their role in inflammation, it is important to understand how microRNA expression may influence the process of bone accrual at implant surfaces during osseointegration.