The calcineurin-NFAT pathway and bone: intriguing new findings.

New findings reveal that the calcineurin-NFAT signaling pathway helps to promote osteoblast differentiation. Three recent papers reveal somewhat different mechanisms by which this could occur. In one study, transduction of calcineurin Aalpha increased expression of osteoblast differentiation markers, including Runx-2. In another study, NFATc1 cooperatively enhanced Osterix activation of the collagen 1a1 promoter, but did not enhance Runx-2 activity; evidence was provided for the formation of a novel NFATc1-Osterix complex. In a third study, expression of nuclear NFATc1 enhanced Wnt signaling. The observation that the Wnt pathway promotes bone formation is intriguing, because NFATc1 also is critical for osteoclastogenesis. The current findings could be relevant for the osteoporosis seen in patients given the calcineurin inhibitor cyclosporine to prevent transplant rejection, although the results need to be reconciled with aspects of the clinical picture.