Direct Down-Regulation of Osteoclast Activation in vitro by Inhibition of Cyclooxygenase-1

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are often prescribed for pain associated with tooth extraction or for inflammatory blockade. The efficacy of NSAIDs include not only analgesic and anti-inflammatory activity but also bone remodeling; for example, NSAIDs delay bone fracture healing in experimental models. NSAIDs inhibit two isozymes of cyclooxygenases (COX), COX-1 and COX-2. We discovered that a COX-1 inhibitor has more direct effectiveness on osteoclast activation than a COX-2 inhibitor. Osteoclasts were prepared from mouse hematopoietic stem cells to clarify the direct effect of NSAIDs on osteoclast differentiation and activation. Treated for 48-hours, COX-1 inhibitor (SC-560), non-selective NSAID (Diclofenac), and COX-2 inhibitor (SC-58125) significantly inhibits the number of tartrate-resistant acid phosphatase-positive cells. Levels of cathepsin K transcripts were almost down-regulated in osteoclasts treated with 10nM SC-560, Diclofenac, and SC-58125, respectively. Pit formation assay revealing the abolition of osteoclastic bone resorption showed a significant reduction with SC-560 and Diclofenac, while SC-58125 showed no inhibition. In this experiment, COX-1 inhibitor showed more efficacy on direct activation of osteoclasts than COX-2 inhibitor did.