Hyperglycemia Induces Osteoclastogenesis and Bone Destruction Through the Activation of Ca 2+ /Calmodulin-Dependent Protein Kinase II

Hyperglycemia induces osteoclastogenesis and bone resorption through complicated, undefined mechanisms. Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) promotes osteoclastogenesis, and could be activated by hyperglycemia. Here, we investigated whether CaMKII is involved in hyperglycemia-induced osteoclastogenesis and subsequent bone resorption. Osteoclast formation, bone resorption, CaMKII expression and phosphorylation were measured under high glucose in vitro and in streptozotocin-induced hyperglycemia rats with or without CaMKII inhibitor KN93. The results showed that 25 mmol/L high glucose in vitro promoted cathepsin K and tartrate-resistant acid phosphatase expression ( p < 0.05) and osteoclast formation ( p < 0.01) associated with enhancing β isoform expression ( p < 0.05) and CaMKII phosphorylation ( p < 0.001). Hyperglycemia promoted the formation of osteoclasts and resorption of trabecular and alveolar bone, and inhibited sizes of femur and mandible associated with enhanced CaMKII phosphorylation ( p < 0.001) in rats. All these changes could be alleviated by KN93. These findings imply that CaMKII participates not only in hyperglycemia-induced osteoclastogenesis and subsequent bone resorption, but also in the hyperglycemia-induced developmental inhibition of bone.