Calcineurin is a protein phosphatase that regulates several physiological processes and is the target for cyclosporine A. Pharmacological inhibition of calcineurin by low concentrations of cyclosporin A increases osteoblast differentiation in vitro and bone mass in vivo. To determine whether calcineurin exerts direct actions on osteoblasts, the authors of a recent study [1] generated mice lacking a calcineurin regulatory subunit selectively in osteoblasts.
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The differentiation of multipotent stemcells of mesodermal origin results in the formation of adipocytes, chondrocytes, osteoblasts, and myoblasts. In humans, osteoporosis and age-related osteopenia are associated with an increase in marrow fat tissue and osteoblast numbers correlated negatively with the number of adipocytes. Osteoblastic differentiation is driven by runx2, and then characterized by the expression of alkaline phosphatase, osteocalcin, and eventually by the mineralization of the extracellular matrix.
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