According to the results of a study in mice, the inflammatory molecule TNF-? (tumor necrosis factor-alpha) could contribute to delayed bone fracture healing in diabetes.
Image: Computer rendered crystal structure of TNF-?.
Diabetes, a condition where the body either does not produce enough, or respond to, insulin, affects at least 171 million people worldwide, a figure that is likely to double by 2030. Long-term complications of diabetes include cardiovascular disease, nerve and blood vessel damage, chronic renal failure, and retinal damage that can lead to blindness.
Diabetes patients often experience low bone density, which is associated with increased risk of bone fractures and delayed fracture repair. To examine how diabetes affects bone, researchers explored bone repair in a mouse model of diabetes. They observed increased levels of inflammatory molecules, including TNF-?, during fracture healing.
The diabetic mice had rapid loss of cartilage in the healing bones, which was due to increased numbers of osteoclasts, cells that remove bone and cartilage. Factors that stimulate osteoclast formation were regulated by both TNF-? and a downstream mediator, FOXO1. These results suggest that diabetes mediated increases in TNF-? and FOXO1 may underlie the impaired healing of diabetic fractures.
The researchers suggest that “TNF-? dysregulation plays a prominent role in the recently identified catabolic events associated with diabetic fracture healing.” In future studies they plan to examine the effect of FOXO1 on mineralized tissue to examine how it may regulate factors that control bone resorption and osteoclastogenesis, in addition to effects it may have on osteoblastic cells.
References:
1. Alblowi J, Kayal RA, Siqueira M, McKenzie E, Krothapalli N, McLean J, Conn J, Nikolajczyk B, Einhorn TA, Gerstenfeld L, Graves DT. High Levels of TNF-? Contribute to Accelerated Loss of Cartilage in Diabetic Fracture Healing. Am J Pathol 2009 175: 1574-1585.
