Led by Lilian Plotkin, PhD, the Plotkin Lab focuses on the role of connexins in the transduction of signals induced by hormonal, pharmacotherapeutic and mechanical stimuli in osteoblasts and osteocytes. For this, the laboratory utilizes in vitro techniques including tissue culture, analysis of protein expression by Western blotting and of gene expression by real time PCR. In addition, ex vivo cultures of bone cells isolated from mice treated with pharmacologic and hormonal agents, and from genetically modified mice are performed. Lastly, genetically modified mice have been generated and their bone phenotype is characterized using in vivo and ex vivo imaging, gene expression techniques and histomorphometric analysis.
As a result of this work, the laboratory has demonstrated that bisphosphonates, agents widely used to treat osteoporosis, prevent osteocyte and osteoblast apoptosis via a novel mechanism that involves opening of connexin43 hemichannel and activation of intracellular signaling molecules. The lab has unveiled a new role of connexin43 on the maintenance of osteocyte viability and in the composition of the bone matrix. Moreover, it has linked for the first time changes on the molecular composition of the cells in bone with cell death and deficient material properties. More recently, the laboratory has begun exploring the interaction between the brain and bone, by testing the consequences of neurological diseases, including epilepsy and fragile X syndrome, in the skeleton using mouse and rat models.