Bone and Cartilage Cell Biology

Our laboratory is interested in the regulation of bone and cartilage cell metabolism by extracellular signals, both chemical and biophysical, the mechanism by which these signals interact with cell membranes and how aging affects these processes. The goals of this research are to gain a better understanding of basic bone and cartilage cell biology, characterize the cellular mechanisms of aging, and broaden our understanding of the pathophysiology of diseases such as osteoporosis and osteoarthritis. Current work focuses on cytosolic Ca2+ regulation and includes studies on the mechanisms by which hormones and biophysical factors interact with the cell membrane to facilitate Ca2+ influx. These studies utilize patch clamp electrophysiology and microspectroflourometry, combined with digital image analysis, to quantify cytosolic Ca2+ dynamics. We also have a strong interest in intercellular communication. Osteoblasts and chondrocytes express the gap junction protein connexin43 and, utilizing indirect immunofluorescence, as well as northern and western blot analysis we have characterized hormonal regulation of connexin43 gene expression in these cells and the role of gap junctional intercellular communication (GJIC) in bone and cartilage function. Furthermore, utilizing antisense techniques we have rendered osteoblastic cells GJIC deficient. These cells display decrease responsiveness to hormonal and biophysical signals and display a decreased ability to differentiate. Thus, gap junctions appear to play a role in signal transduction and cellular differentiation. A long term goal of our research is to examine the affect of aging on the cell processes outlined above. Thus, we have undertaken projects which will identify age-induced changes in signal transduction in bone cells. This work has important implications regarding the pathogenesis of Type II (age-related) osteoporosis. Finally, we are also examining the role of gap junctional communiation in tumorigenesis and bone metastasis. We have found the the metastaic potential of breast cancer cells is at least partly related alterations in gap junction expression and function.