TABLE 3.

Selected downregulated genes in MSCs cultured on Ti-AM + Bru compared to Ti-AM under osteogenic conditions, with their biological roles and potential contributions to early osseointegration.

Gene	Role	Pro-osteointegrative role in early phase
BMP8B	Bone morphogenetic protein 8B – involved in osteogenesis and bone formation	Downregulation of BMP8B may indicate that the initial osteogenic signaling is being modulated after early activation, allowing the bone healing process to stabilize and mature
WNT7B	Part of the wnt signaling pathway, critical for osteoblast differentiation and bone formation	Downregulation of WNT7B suggests a shift from early-stage osteogenesis to more regulated and stable bone formation, aiding in the long-term integration of the implant
NOTCH4	A gene involved in cell differentiation, particularly osteoblast differentiation	Downregulation of NOTCH4 implies that the initial osteoblast differentiation phase is transitioning into a more stable bone remodeling phase, essential for implant osseointegration
ICAM5	Intercellular adhesion molecule 5, involved in immune cell adhesion and recruitment	Downregulation of ICAM5 indicates that the acute inflammatory response is subsiding, which is necessary for a balanced immune response, crucial for the successful integration of the implant
SAA2	Serum amyloid A2, an acute-phase protein that is upregulated during inflammation	Downregulation of SAA2 suggests a decrease in inflammation, signaling the transition from the inflammatory phase to tissue repair and remodeling, which is critical for osseointegration
GUSBP3	Involved in immune modulation and cellular stress response	Downregulation of GUSBP3 reflects a reduction in the early stress response, suggesting that the cellular environment is stabilizing and becoming more conducive to bone formation and healing