Enhanced osseointegration of titanium implant through the local delivery of transcription factor SATB2.

Titanium implants are widely used in dentistry and orthopedic surgery. Nevertheless, bone regeneration around the implant is a relatively slow process, after placement. This study assessed whether SATB2 can enhance osseointegration of a titanium implant. To determine the effect of SATB2 in implant integration, two different viruses encoding SATB2 (PBABE-Satb2 virus or RCAS-Satb2 virus) were locally administered to the bone defect prior to titanium implant placement in our established transgenic TVA mice. Seven and 21 days post implantation, the femurs were isolated for quantitative real-time RT-PCR, H&E staining, immunohistochemical (IHC) staining, and microcomputed tomography (microCT) analysis. Quantitative real-time RT-PCR results demonstrated that the in vivo overexpression of SATB2 enhanced expression levels of potent osteogenic transcription factors and bone matrix proteins. We also found that 21 days after implantation, there were no significant differences in the expression levels of SATB2, Osx, Runx2, COLI, OC, and BSP between the RCAS-Satb2 group and the RCAS group. Histological analysis showed that SATB2 overexpression significantly enhanced new bone formation and bone-to-implant contact after implantation. IHC staining analysis revealed that forced expression of SATB2 increased the number of BSP-positive cells surrounding the implant. MicroCT analysis demonstrated that in vivo overexpression of SATB2 significantly increased the density of the newly formed bone surrounding the implant. These results conclude that in vivo overexpression of SATB2 significantly accelerates osseointegration of titanium implants and SATB2 can serve as a potent molecule in promoting tissue regeneration.

Studies on the role of sodium/hydrogen exchange system in myocardial ischemia-reperfusion injury.

This study aimed at the exploration of the relationship between Na(+)-H+ exchange system and myocardial ischemia-reperfusion injury (MRI) in an attempt to provide a theoretic basis for the prevention and treatment of MRI. We used the isolated working guinea pig hearts as the experimental model to mimick cardiopulmonary bypass, which included 120 min hypothermic ischemic cardioplegic arrest followed by 60 min normothermic reperfusion. The hearts were divided into 2 groups: the control group receiving St. Thomas' Hospital Solution (STS) and the treated group receiving STS + amiloride, a Na(+)-H+ exchange blocker. The results showed that during reperfusion, [Na+]i and [Ca2+]i overloads, poor recovery of cardiac function, increases in CPK release and OFR generation, reduction of ATP content and serious damage of ultrastructure were seen in group 1; whereas there were no [Na+]i and [Ca2+]i overloads and better recovery of cardiac function accompanied by improved results of biochemical assay and less damage of ultrastructure was found in group 2. Our study indicates that amiloride can inhibit Na(+)-H+ exchange system in cardiac cells during early reperfusion period, which prevents [Na+]i overload produced by Na(+)-H+ exchange, and stops Na(+)-Ca2+ exchange activated by high level of [Na+]i, thus attenuating [Ca2+]i overload caused by Na(+)-Ca2+ exchange and myocardial injury. Therefore, we conclude that Na(+)-H+ exchange blocker, amiloride, can exert significant protective effects on MRI and its use may prove to be a new clinical approach to prevention and cure of MRI.