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Background and Hypothesis: The Ca+2/calmodulin (CaM)-mediated protein kinase kinase 2 (CaMKK2) is a multi-functional kinase with effects on cell proliferation, differentiation and metabolism. The role of CaMKK2 in bone has been explored with its ablation favoring osteoblasts to osteoclasts and bone mass accrual as observed in Camkk2-/mice, or following its inhibition by STO-609. One outstanding question is whether the anabolic effects of CaMKK2 are bone-cell intrinsic. While analyzing mice harboring bone-cell specific deletion of CaMKK2, we observed a high bone mass phenotype when the kinase is deleted from osteocytes, the most abundant cells within the bone. We therefore hypothesized that the loss of CaMKK2 enhances osteocyte differentiation.

Role of CaMKK2 in Osteocytes within the Bone Microenvironment