Parathyroid hormone modulates the response of osteoblast-like cells to mechanical stimulation

Mechanical loading stimulates many responses in hone and osteoblasts associ ated with osteogenesis. Since loading and parathyroid hormone (PTH) activat e similar signaling pathways in osteoblasts, we postulate that PTH can pote ntiate the effects of mechanical stimulation. Using an in vitro four-point bending device, we found that expression of COX-2, the inducible isoform of cyclooxygenase, was dependent on fluid forces generated across the culture plate, but not physiologic levels of strain in MC3T3-E1 osteoblast-like ce lls. Addition of 50 nM PTH during loading increased COX-2 expression at bot h subthreshold and threshold levels of fluid forces compared with either st imuli alone. We also demonstrated that application of fluid shear to MC3T3- E1 cells induced a rapid increase in [Ca2+](i). Although PTH did not signif icantly change [Ca2+](i) levels, flow and PTH did produce a significantly g reater [Ca2+](i) response and increased the number of responding cells than is found in fluid shear alone, The [Ca2+](i) response to these stimuli was significantly decreased when the mechanosensitive channel inhibitor, gadol inium, was present. These studies indicate that PTH increases the cellular responses of osteoblasts to mechanical loading. Furthermore, this response may be mediated by alterations in [Ca2+](i) by modulating the mechanosensit ive channel.