Osteocytes as multifunctional cells.

Bone is often thought of as being a passive, inactive tissue like a skeleton hanging in the anatomy lab. Often, bone tissue is envisioned statically in terms of two dimensions similar to a 'shapshot' of a histology slide. However, quite to the contrary, bone undergoes considerable turnover as compared to other organs in the body. Modeling during growth is dramatic and even in adult bone, 2-5% turnover per year occurs in the long bone and 30% in alveolar bone. Any experimental approach can bias or have an effect on human interpretations of biological processes and events. Scientists should always be constantly asking how our perceptions are being modified by our experimental approaches. Bone biologists can easily visualize in vitro and in vivo the dynamic nature of osteoclasts with their resorption lacunae and rapid removal of bone, which occurs relatively rapidly in days. Osteoblasts are less dynamic, with new bone formation occurring in weeks. Many individuals still view the osteocyte as being a passive, inactive cell that merely acts as a 'place holder' in bone. Again, this perspective has most likely been perpetuated by histological approaches to the study of bone. Decades ago there were pioneers in the bone field who proposed that the osteocyte is not a passive cell, but a cell with the potential to have several functions. Credit is given to several of these pioneers below, while contrasting with most recent advances due to the availability of state of the art technology. Osteocytes, with their distribution throughout the bone matrix and their high degree of interconnectivity, are ideally positioned within the bone matrix to sense mechanical strain and translate that strain into biochemical signals of resorp-tion or formation related to the intensity and distribution of the strain signals 1. Rubin and Lanyon in 1984 and 1985 developed and characterized the mechanical strain parameters for inducing bone formation or bone resorption in vivo 2,3. However, the major challenge has been and still is to translate in vivo parameters of mechanical loading to in vitro cell culture models. With the advent of microCT, finite element analysis can be performed. Combined with means to follow gene and protein expression over time, it is now possible to correlate magnitude of strain with biochemical signals and with the final biological response 4,5. Over five decades ago, Heller-Steinberg proposed that osteocytes may resorb their lacunar wall under certain conditions 6. The term "osteolytic osteolysis" …