An in vitro model of the mechanical regulation of bone homeostasis: Effects of cyclic pressure on select bone cell functions

In an attempt to elucidate the cellular/molecular-level correlations between mechanical stimuli and bone homeostasis (a multi-cellular process), the present in vitro study examined and compared the effects of cyclic pressure on select functions of several cell types using a custom-made, computer-interfaced cyclic pressure apparatus, and molecular biology and biochemistry techniques.; The results demonstrated unique relationships between characteristic parameters of mechanical loading and osteoblast functions. Osteoblast proliferation was dependent on the frequency and on the duration of the applied cyclic pressure stimulus (10 kPa –40 kPa); specifically, decreased cell proliferation was only observed when these cells were exposed to cyclic pressure at 1.0 Hz (but not at 0.25 Hz) frequency for 1 hour (but not for 20 minutes) daily for 5 days. Furthermore, the results of the present study provided the first evidence that exposure to cyclic pressure for 1 hour/day for up to 19 consecutive days stimulated osteoblast functions pertinent to new bone formation; namely, transcription and translation for matrix proteins, and concentration of calcium in this extracellular matrix were increased following exposure to the cyclic pressure tested.; In addition, compared to controls, the number of osteoclastic cells (differentiated from bone marrow precursors) was significantly (p < 0.05) lower only when bone marrow cells were exposed to cyclic pressure (10–40 kPa at 1.0 Hz). Moreover, exposure of bone marrow cells to cyclic pressure for 1 hour daily for 7 consecutive days resulted in significantly (p < 0.05) lower osteoclastic bone resorption and in lower mRNA expression for interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α), cytokines that are known activators of osteoclast function.; The results of the present in vitro study are consistent with findings of clinical and in vivo animal studies which demonstrated that the presence (and absence) of loading on the skeleton had positive (and negative) effects, respectively, on bone homeostasis. In addition to contributing basic scientific knowledge to bone physiology, the present thesis research provided cellular/molecular insight into the correlation(s) between mechanical loading and bone homeostasis.