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CaMKK2 Inhibition in Enhancing Bone Fracture Healing

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Technical Report,15 Aug 2013,14 Jul 2014

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Indiana University Bloomington United States

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Fracture healing is a chief medical concern for active-duty military personnel as well as aging combat veterans, highlighting a highly critical need for novel therapies to treat this condition. A recent serendipitous discovery that genetic ablation of Ca2calmodulin CaM dependent protein kinase kinase 2 CaMKK2 has duel effects on anabolic and catabolic pathways of bone remodeling has led to the idea that its pharmacological inhibition could serve as an efficacious therapeutic strategy to promote efficient fracture healing. STO-609 is a selective, cell-permeable pharmacological inhibitor of CaMKK2 that has been successfully tested in vivo in mice. Hence the goal of this proposal is to develop STO-609-mediated inhibition of CaMKK2 as an efficacious therapeutic strategy to promote accelerated fracture healing and recovery. During the first phase of the award period, we performed a pilot study to establish the following 1 Reliable and reproducible surgical procedures for creating a transverse femoral fracture and fixing it with an intramedullary device. 2 The treatment protocol for following the animals for the appropriate follow-up period. 3 The collection and analysis of the femur for assessing fracture healing.

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