The effects of the receptor for advanced glycation end products (RAGE) on bone metabolism under physiological and diabetic conditions

It has been reported that AGEs and the receptor for AGEs (RAGEs) have been linked to the pathogenesis of diabetic microangiopathy. However, the relationship between RAGE and alteration in bone metabolism is unclear. Therefore, in order to determine the role of RAGE in bone metabolism, we investigated the effects of RAGE deletion on bone metabolism under physiological and diabetic conditions using RAGE knockout mice (RAGE-KO). Eight-week-old male RAGE-KO and wild-type littermates (WT) were intraperitoneally injected with either streptozotocin or vehicle. Mice were classified into four groups: (1) nondiabetic WT; (2) nondiabetic RAGE-KO; (3) diabetic WT; and (4) diabetic RAGE-KO. After 12 weeks of streptozotocin or vehicle treatment, the physical properties of femora and the static and dynamic parameters of bone histomorphometry of tibiae were assessed. The deletion of RAGE affected neither body weights nor hemoglobin A1c levels. RAGE deletion resulted in increased bone mineral density due to decreased osteoclast function under physiological conditions that is no accumulation of AGEs. In contrast, lacking RAGE did not affect the alteration in bone metabolism under diabetic conditions, suggesting that AGEs–RAGE interaction may not be involved in the pathogenesis of diabetic osteopenia, although RAGE plays a crucial role in bone metabolism.