Serum 1alpha,25-dihydroxyvitamin D3 accumulates into the fracture callus during rat femoral fracture healing.
1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is thought to be an important systemic factor in the fracture repair process, but the mechanism of action of 1,25(OH)2D3 has not been clearly defined. In this study, the role of 1,25(OH)2D3 in the fracture repair process was analyzed in a rat closed femoral fracture model. The plasma concentration of 1,25(OH)2D3 rapidly decreased on day 3 and continued to decrease to 10 days after fracture. We assessed whether this decrease was based on the accelerated degradation or retardation of the synthesis rate of 1,25(OH)2D3, from 25(OH)D3. After radiolabeled 3H-1,25(OH)2D3 or 3H-25(OH)D3 was injected i.v. into fractured or control (unfractured) rats, the concentrations of 25(OH)D3 and 1,25(OH)2D3 metabolites were measured by HPLC. The plasma concentrations of these radiolabeled metabolites in fractured group were similar to those in control rats early after operation. However, radioactivity in the femurs of fractured rats was higher than that of the control group. Furthermore, the radioactivity was concentrated in the callus of the fractured group analyzed by autoradiography. 1,25(OH)2D3 receptor gene expression was detected early after fracture and, additionally, both in the soft and hard callus on days 7 and 13 after fracture. These results showed that the rapid disappearance of 1,25(OH)2D3 in the early stages after fracture was not due to either increased degradation or decreased synthesis of 1,25(OH)2D3, but rather to increased consumption. Further, these results suggest the possibility that plasma 1,25(OH)2D3 becomes localized in the callus and may regulate cellular events in the process of fracture healing.
Jingushi
S
S
Department of Orthopaedic Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan. jingushi@ortho.med.kyushu-u.ac.jp
Iwaki
A
A
Higuchi
O
O
Azuma
Y
Y
Ohta
T
T
Shida
J I
JI
Izumi
T
T
Ikenoue
T
T
Sugioka
Y
Y
Iwamoto
Y
Y
D000818:Animals; D001345:Autoradiography; D002112:Calcifediol / Q000097:blood / Q000378:metabolism; D002117:Calcitriol / Q000097:blood* / Q000378:metabolism*; D002356:Cartilage / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005264:Femoral Fractures / Q000378:metabolism*; D005269:Femur / Q000737:chemistry / Q000378:metabolism; D017102:Fracture Healing / Q000502:physiology*; D007700:Kinetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000235:genetics; D014316:Tritium
D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D014316:Tritium; D002117:Calcitriol; D002112:Calcifediol