Statement of Purpose: Osseointegration is a structural and functional contact between a load-bearing implant and living bone, which ensures the success of dental and orthopaedic implants. A critical stage in osseointegration is primary bone remodeling. It requires the balance in the coupling system between bone formation and bone resorption. Understanding the coupling mechanisms underlying bone remodeling and investigating the coupling factors involved will allow us to improve the osseointegration and develop better dental or orthopaedic implants. A new class of molecules has been recently reported to act as coupling factors in remodeling—the semaphorins. This project is focused on Sema4D, which has been reported to inhibit bone formation without affecting osteoclastogenesis during normal bone remodeling, as well as Sema3C, which has been less studies in the context of bone. Our lab previously found that Sema3C mRNA expression is upregulated in osteoblasts. Ti implants with rougher a n d / or hydrophilic surfaces can induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) or other osteoblast progenitor cells. Therefore, our goal was to determine the effect of semaphorins on osteogenic differentiation of hMSCs induced by microstructured Ti implant surfaces.