Effects of Propofol on the Formation and Activity of Osteoclast-Like Cells

Propofol affects the central nervous system rapidly and works as an anesthetic. After intravenous administration, cells resident in bone tissues are also exposed to propofol. Osteoclasts can form actin rings on bone surfaces and express carbonic anhydrase II (Car2), cathepsin K (Ctsk), and matrix metalloproteinase-9 (Mmp9), which are enzymes associated with bone decomposition and play a central role in bone resorption. This study examined the expression of enzymes involved in bone resorption and actin ring formation in cells stimulated by propofol to elucidate the difference in the effects of continuous and temporary propofol stimulation on osteoclast resorption ability. RAW264.7 cells were stimulated with propofol emulsified injection solution or 2,6-diisopropylphenol (non-emulsified propofol) for 5 h, 1.5 days, or 4 days in the presence of the receptor activator of nuclear factor kappa B ligand (RANKL). Osteoclast-like cells were confirmed by staining with tartrate-resistant acid phosphatase (TRAP). Actin rings were detected using fluorescent staining. The bone resorption enzymes were detected using real-time PCR and Western blotting. The mineral resorption activity was assessed using the pit formation assay. Continuous propofol stimulation for more than 1.5 days suppressed actin ring formation and Car2, Ctsk, and Mmp9 expression. Propofol stimulation for 5 h had no suppressive effects, whereas prolonged stimulation (> 1.5 days) decreased the area of resorption pits. There was no marked difference in the suppressive effects of emulsified versus non-emulsified propofol on TRAP-positive multinuclear cell formation. Our in vitro study indicated that exposure of RAW264.7 cells to propofol for several hours did not affect their subsequent RANKL-induced differentiation into osteoclast-like cells, thus maintaining their bone resorption function. However, continuing propofol exposure suppressed the formation and activity of osteoclast-like cells.