The Effects of the Inhibition of Connexin 43 on Pre-Osteoblasts and Their Response to Mechanical Stimulation

It is well established that bone can adapt to the demands of daily mechanical usage. Mechanical loading can result in bone formation depending on the magnitude, duration, and frequency. Unloading, which can occur during bed rest, micro-gravity exposure and a variety of clinical conditions, can result in bone resorption. In vitro studies have demonstrated that osteoblasts and osteocytes respond to mechanical stimulation, especially oscillatory fluid shear stress. Mechano-responses have included increases in inter- and intra-cellular communication through gap junctions and soluble factors such as nitric oxide and prostaglandin E₂ [1]. Bone cell gap junctions are primarily comprised of connexin 43 (Cx43). Mice lacking Cx43 have an osteopenic phenotype and when subjected to cyclic 4 pt. bending loads have an increased tibia bone marrow area [2, 3]. These observations may represent altered cell signaling. To investigate the role of Cx43 in cell signaling and bone mechanotransduction the Cx43 gene was silenced in MC3T3-E1 pre-osteoblast cells subjected to oscillatory fluid shear stress.