title: Malfunction of bone marrow-derived osteoclasts and the delay of bone fracture healing in diabetic mice.
abstract: It is well known that bone fracture healing is delayed in diabetes mellitus, but the mechanism remains to be elucidated. Since several studies have demonstrated that diabetes causes abnormalities in bone marrow-derived cells, we used the streptozotocin (STZ)-induced diabetic mouse model after bone marrow transfer from green fluorescent protein (GFP) transgenic mice, and examined fracture healing. Compared with nondiabetic mice, diabetic mice at 3 weeks after fracture showed a decrease in mineralized callus, with the remainder consisting of cartilage. Bone formation parameters and mineralization rate were not altered in the STZ mice, but bone resorption parameters were significantly decreased. Therefore, the delayed bone formation in the STZ mice may have resulted from an impairment of cartilage resorption. Interestingly, we found that 80% of the osteoclasts in the callus were derived from bone marrow and the sizes of the osteoclasts as well as the resorption pits formed were significantly smaller in the diabetic mice. Moreover, transcript analysis using RNA isolated by laser capture microdissection (LCM) showed that the expression of DC-STAMP, a putative pivotal gene for osteoclast fusion, was decreased in osteoclasts from diabetic mice. Since the sustainability of osteoclast function depends on the controlled renewal of multinuclear osteoclasts, impaired osteoclast function in diabetes may contribute to decreased cartilage resorption and delayed endochondral ossification.
authors.affiliation: Department of Orthopedic Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan. tkasa@belle.shiga-med.ac.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kasahara
authors.forename: Sinji
authors.initials: S
authors.lastname: Imai
authors.forename: Hideto
authors.initials: H
authors.lastname: Kojima
authors.forename: Miwako
authors.initials: M
authors.lastname: Katagi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chan
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Matsusue
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D001862:Bone Resorption; D002356:Cartilage / Q000166:cytology / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D017102:Fracture Healing / Q000502:physiology*; D050723:Fractures, Bone / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*