The role of bone morphogenetic protein 2 in SMA-directed angiogenesis during distraction osteogenesis

Bone is one of the few organs capable of regeneration after a substantial injury. As the bone heals itself after trauma, the coupling of angiogenesis to osteogenesis is crucial for the restoration of the skeletal tissue. In prior studies we have shown that Bone Morphogenetic Protein 2 (BMP2), a potent agonist for skeletal formation is expressed by vessels making it a prime candidate that links the morphogenesis of the two tissues. To investigate the role of BMP2 in the coordination of vessel and bone formation, we used a tamoxifen inducible Smooth Muscle Actin (SMA) promoter that conditionally expresses Cre recombinases crossed with a BMP2 floxed mouse in order to conditionally delete the BMP2 gene in smooth muscle actin (SMA) expressing cells. Using the mouse femur as our model for bone regeneration, we performed a surgical technique called distraction osteogenesis (DO) where an osteotomy is created followed by distraction or a gradual separation of the two pieces of bone. This primarily promotes intramembranous ossification at the osteotomy site by mechanical stimulation. Tamoxifen treatment started at day 6 and continued throughout the experiment. At post-operative days 3, 7, 12, 17, 24, and 31, we analyzed the bone and vessel formation by plain X-ray, micro-computed tomography (µCT) and vascular contrast enhanced µCT, and quantitative polymerase chain reaction (qPCR) of selective genes. We assessed both the femur and surrounding tissue to obtain qualitative and quantitative assessments for skeletal and vascular formation. Our results demonstrated that the deletion of BMP2 in vascular tissue resulted in a reduction of angiogenesis in vivo followed by a decrease in skeletal tissue development

Guaranteed Cost Tracking for Uncertain Coupled Multi-agent Systems Using Consensus over a Directed Graph

This paper considers the leader-follower control problem for a linear multi-agent system with directed communication topology and linear nonidentical uncertain coupling subject to integral quadratic constraints (IQCs). A consensus-type control protocol is proposed based on each agent's states relative to its neighbors and leader's state relative to agents which observe the leader. A sufficient condition is obtained by overbounding the cost function. Based on this sufficient condition, a computational algorithm is introduced to minimize the proposed guaranteed bound on tracking performance, which yields a suboptimal bound on the system consensus control and tracking performance. The effectiveness of the proposed method is demonstrated using a simulation example.Comment: Accepted for presentation at the 2013 Australian Control conferenc