Deletion of FOXO1 in chondrocytes rescues the effect of diabetes on mechanical strength in fracture healing

Diabetes increases the risk of fracture, impairs fracture healing and causes rapid loss of the fracture callus cartilage, which was linked to increased FOXO1 expression in chondrocytes. We recently demonstrated that deletion of FOXO1 in chondrocytes blocked the premature removal of cartilage associa...

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Bibliographic Details
Published in:Bone (New York, N.Y.) N.Y.), 2019-06, Vol.123, p.159-167
Main Authors: Lu, Yongjian, Alharbi, Mohammed, Zhang, Citong, O'Connor, J. Patrick, Graves, Dana T.
Format: Article
Language:English
Subjects:
Bone
Chondrocyte
Diabetic
Forkhead
FOXO
Hyperglycemia
Long bone
Mechanical testing
Transcription factor
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Summary:Diabetes increases the risk of fracture, impairs fracture healing and causes rapid loss of the fracture callus cartilage, which was linked to increased FOXO1 expression in chondrocytes. We recently demonstrated that deletion of FOXO1 in chondrocytes blocked the premature removal of cartilage associated with endochondral bone formation during fracture healing. However, the ultimate impact of this deletion on mechanical strength was not investigated and remains unknown. Closed fractures were induced in Col2α1Cre+.FOXO1L/L mice with lineage specific deletion of FOXO1 in chondrocytes compared to littermate controls. Type 1 diabetes was induced by multiple low dose streptozotocin treatment. Thirty-five days after fracture micro CT analysis showed that diabetes significantly reduced callus volume and bone volume (P 
ISSN:8756-3282
1873-2763
DOI:10.1016/j.bone.2019.03.026