Bone tissue experiences continued remodelling in response to changes in its biochemical and biophysical environment. Given the finite lifespan of osteoblasts, this continued bone formation requires replenishment from a progenitor population. Although this is largely believed to be from a skeletal stem cell population, given the limitation in in-vivo markers for this cell type, progress in demonstrating this mechanism is limited. Therefore, we characterized the LepR-Cre mouse strain and evaluated whether LepR positive cells are the progenitor population and if they contribute to the osteoblast population over time and in mechanically-induced bone formation in-vivo. Transgenic mouse strains; B6.129(Cg)-Leprtm2(cre)Rck/J to study LepR-expressing cells and B6.Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze/J as a reporter strain were obtained from Jackson Laboratories. Characterization studies were performed on LepR:tdTomato mice at embryonic stage (19.5dpc), 8 and 12 weeks old. Mice (12 weeks old) were subjected to compressive tibia loading with a 11N peak load for 40 cycles, every other day for 2 weeks. Histological analysis reveal that LepR is expressed from the embryonic stage in various organs including bones. LepR positive cells are found around blood vessels and on bone surfaces. Flow cytometry analysis show the amount of LepR positive cells negative for CD45 and Ter-119 markers inside the bone marrow increases over time and following tibial loading. Mechanical loading induces an increase in bone mass and bone parameters. This model allows us to track and evaluate the role of LepR positive cells as bone forming cells, and to decipher the role of these cells in mechanically-induced bone formation.
Wear of polymeric glenoid components has been identified as a cause of loosening and failure of shoulder implants1,2 in vivo. A small number of shoulder joint simulators have been built for in vitro wear testing, however none have been capable of testing with physiological motion patterns in three axes and with physiological loading. The Newcastle Shoulder Wear Simulator was designed with three axes of motion, which are programmable so that different activities of daily living might be replicated. The simulator uses three pneumatic cylinders with integral position encoders to move five shoulder prostheses simultaneously in the flexion-extension, abduction-adduction, and internal-external rotation axes. Axial loading is applied with pneumatic cylinders supplied from a pneumatic proportional valve via a manifold, which also supplies a sixth static control station. In order to establish if that the machine can actually perform as intended, commissioning trials were conducted replicating lifting a 0.5 Kg weight to head height as a daily living activity. During the commissioning trials JRI Orthopaedics Reverse VAIOS shoulder prostheses were tested in 50% bovine serum at ambient temperature. The results show that the shoulder joint wear simulator can satisfactorily reproduce a daily living activity deliberately selected for having a large range of motion and loading. Other daily activities, such as drinking from a mug, are less demanding in the ranges of motion and loading and represent no difficulty in being reproduced on the simulator. Now successfully commissioned, this new multi-station shoulder wear simulator can wear test current and new designs of shoulder prosthesis in vitro
