Recruitment of osteogenic cells to bone formation sites during development and fracture repair.

Recruitment of osteoblast lineage cells to their bone-forming locations is essential for skeletal development and fracture healing. In developing bones, osteoprogenitor cells invade the cartilage mold to establish the primary ossification center. Similarly, osteogenic cells infiltrate and populate the callus tissue that is formed following an injury. Proper bone development and successful fracture repair must, therefore, rely on controlled temporal and spatial navigation cues guiding the cells to the sites where new bone formation is needed. Some cellular mechanisms and molecular pathways involved have been elucidated.

[Recruitment of osteogenic cells to bone formation sites during development and fracture repair - German Version]. / Rekrutierung osteogener Zellen an den Ort der Knochenbildung während Entwicklung und Frakturheilung.

Recruitment of osteoblast lineage cells to their bone-forming locations is essential for skeletal development and fracture healing. In developing bones, osteoprogenitor cells invade the cartilage mold to establish the primary ossification center. Similarly, osteogenic cells infiltrate and populate the callus tissue that is formed following an injury. Proper bone development and successful fracture repair must, therefore, rely on controlled temporal and spatial navigation cues guiding the cells to the sites where new bone formation is needed. Some cellular mechanisms and molecular pathways involved have been elucidated.

Spatiotemporal distribution of thrombospondin-4 and -5 in cartilage during endochondral bone formation and repair.

During skeletal development most bones are first formed as cartilage templates, which are gradually replaced by bone. If later in life those bones break, temporary cartilage structures emerge to bridge the fractured ends, guiding the regenerative process. This bone formation process, known as endochondral ossification (EO), has been widely studied for its potential to reveal factors that might be used to treat patients with large bone defects. The extracellular matrix of cartilage consists of different types of collagens, proteoglycans and a variety of non-collagenous proteins that organise the collagen fibers in complex networks. Thrombospondin-5, also known as cartilage oligomeric matrix protein (TSP-5/COMP) is abundant in cartilage, where it has been described to enhance collagen fibrillogenesis and to interact with a variety of growth factors, matrix proteins and cellular receptors. However, very little is known about the skeletal distribution of its homologue thrombospondin-4 (TSP-4). In our study, we compared the spatiotemporal expression of TSP-5 and TSP-4 during postnatal bone formation and fracture healing. Our results indicate that in both these settings, TSP-5 distributes across all layers of the transient cartilage, while the localisation of TSP-4 is restricted to the population of hypertrophic chondrocytes. Furthermore, in fractured bones we observed TSP-4 sparsely distributed in the periosteum, while TSP-5 was absent. Last, we analysed the chemoattractant effects of the two proteins on endothelial cells and bone marrow stem cells and hypothesised that, of the two thrombospondins, only TSP-4 might promote blood vessel invasion during ossification. We conclude that TSP-4 is a novel factor involved in bone formation. These findings reveal TSP-4 as an attractive candidate to be evaluated for bone tissue engineering purposes.

Bending stiffness of healing fractures can be calculated from quantitative computed tomography.

This paper revisits the relationship between bone densitometry and fracture healing by using quantitative computed tomography (QCT) to assess bone density. In recent time the correlation between bone mineral density (BMD) and mechanical stability of healing bone has been investigated with the purpose to predict mechanical properties of healing fractures--such as their loading capability--from data which can be collected non-invasive. One goal is to obtain a functional dependency between data obtained from QCT and the mechanical properties. In this study the computation of the mechanical stability of fractures from data obtained by QCT is proved to be reliable (r2 = 0.947 and P < 0.0001). As one result most dependencies between mechanical data and stiffness are not linear but quadratic (r2 > 0.72, P < 0.0005). The only linear dependencies are found between the second polar moment of inertia (Ip), calculated from geometric midpoint and center of mass (r2 = 0.688, P = 0.0052 and r2 = 0.677, P = 0.0010), and the average density (r2 = 0.836, P < 0.0001) versus bending stiffness. A functional dependency between bending stiffness and bone mineral content (BMC) of the fracture area in the fracture gap can be provided. The data presented in this work has been computed by a new algorithm developed by the author for detecting the fracture area of minimal density automatically in three-dimensional data obtained from QCT.