Disordered osteoclast formation in RAGE-deficient mouse establishes an essential role for RAGE in diabetes related bone loss.
The mechanisms underlying diabetes-mediated bone loss are not well defined. It has been reported that the advanced glycation endproducts (AGEs) and receptor for AGEs (RAGEs) are involved in diabetic complications. Here, mice deficient in RAGE were used as a model for investigating the effects of RAGE on bone mass. We found that RAGE-/- mice have a significantly increased bone mass and bone biomechanical strength and a decreased number of osteoclasts compared to wild-type mice. The serum levels of IL-6 and bone breakdown marker pyridinoline were significantly decreased in RAGE-/- mice. RAGE-/- mice maintain bone mass following ovariectomy, whereas wild-type mice lose bone mass. Furthermore, osteoclast-like cells do express RAGE mRNA. Our data therefore indicate that RAGE serves as a positive factor to regulate the osteoclast formation, directly implicates a role for RAGE in diabetes-promoted bone destruction, and documents that the AGE-RAGE interaction may account for diabetes associated bone loss.
Ding
Ke-Hong
KH
Department of Medicine, Medical College of Georgia, Augusta, GA, USA.
Wang
Zai-Zhao
ZZ
Hamrick
Mark W
MW
Deng
Zhong-Bin
ZB
Zhou
Li
L
Kang
Baolin
B
Yan
Sheng-Li
SL
She
Jin-Xiong
JX
Stern
David M
DM
Isales
Carlos M
CM
Mi
Qing-Sheng
QS
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology*; D048909:Diabetes Complications / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000172:deficiency*
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic