Magic™ Anti-BGLAP monoclonal antibody, clone N29723PT2

Collagen cross-linking, as a form of collagen post-translational modification, plays a crucial role in maintaining bone mechanical properties as well as in regulating cell biological functions. Shifts in cross-links profile are found apparently correlated to kinds of skeletal pathology and diseases, whereas little is known about the relationship between collagen cross-links and osteogenesis. Here, we hypothesized that the inhibition of collagen cross-links could impair skeletal microstructure and inhibit osteogenesis. A mouse model of collagen cross-linking defects has been established using subcutaneous injection of 350mg/kg -aminopropionitrile (BAPN) daily for 4 weeks, and same dose of phosphate buffered saline (PBS) served as control group. The analysis of bone microstructural parameters revealed a significant decrease of bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), and increase of bone surface ratio (BS/BV), structure model index (SMI) as well as trabecular separation (Tb.Sp) in the experimental group (p<0.05), whereas there was no difference observed in bone mineral density (BMD). Histological staining displayed that the BAPN treatment caused thinner trabeculae and decrease of collagen content in proximal tibiae. The analysis of osteogenesis PCR (Polymerase Chain Reaction) array reflected that BAPN remarkably influenced the expression of Alpl, Bglap, Bgn, Bmp5, Col10a1, Col1a1, Col1a2, Col5a1, Itga2b, and Serpinh1. The results of immunohistochemistry displayed a significant reduction in the mean optical densities of OCN and COL1 at the presence of BAPN. The overall results of this study suggested that BAPN alters bone microstructure and hinders the expression of osteogenic genes without affecting mineralization processes, indicating the influences of collagen cross-links on osteogenesis may be a potential pathological mechanism in skeletal diseases.

The aim of this study was to evaluate the in vivo biocompatibility of a biphasic calcium phosphate (BCP) bone graft substitute consisting of 60% hydroxyapatite and 40% beta-tricalcium phosphate (beta-TCP) in comparison to a pure beta-TCP of identical shape and porosity. The materials were evaluated using an established rat cranial defect model in 24 animals. One bone defect with a diameter of 5 mm was created per animal. The defects were filled with either BCP or beta-TCP and left to heal for 4 weeks. Twelve samples (6 per material) were processed for histological evaluation and immunohistochemistry. The remaining 12 samples were processed for mRNA expression analysis. No signs of inflammation or adverse material reactions were detected. New bone formation in the former defect site did not differ between the two groups (BCP: 49.2%; beta-TCP: 52.4%). Osteoblast-like and TRAP-positive osteoclast-like cells were found at the surface of the bone graft substitute granules. The beta-TCP group showed significantly higher mRNA levels for the bone resorption marker Acp5 and osteogenic differentiation marker Runx2. The expression of IGF1, IGF2, VEGF, Phex, Alp1, Col1, Col2, Bglap and MMP8 did not differ between the groups. The in vivo biocompatibility of BCP is to a large part identical to those of TCP. Within the limitation of the animal model, the implantation study shows that BCP can be used as bone graft substitute, due to the fact that the material integrates into tissue, remains stable in the implantation bed and serves as an osteoconductive scaffold. (C) 2014 Elsevier GmbH. All rights reserved.