Article

Effects of low-dose, intermittent treatment with recombinant human parathyroid hormone (1-34) on chondrogenesis in a model of experimental fracture healing.

Department of Orthopaedic Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8677, Japan.
Bone (impact factor: 4.02). 12/2005; 37(5):711-9. DOI:10.1016/j.bone.2005.06.013 pp.711-9
Source: PubMed

ABSTRACT Recent studies have demonstrated that intermittent administration of parathyroid hormone (PTH) enhances osteogenesis (hard callus formation) and increases mechanical strength in experimental fracture healing. Thus far, however, effects of PTH on chondrogenesis (soft callus formation) during fracture healing have not been fully elucidated. In the present study, we analyzed the underlying molecular mechanism by which exogenous PTH would affect chondrogenesis in a model of experimental fracture healing. Unilateral femoral fractures were produced in 2-month-old Sprague-Dawley rats. Daily subcutaneous injections of 10 microg/kg of recombinant human PTH(1-34) [rhPTH(1-34)] were administered over a 28-day period of fracture healing. Control animals were injected with vehicle solution (normal saline) alone. The results showed that, on day 14 after fracture, cartilage area in the PTH-treated group was significantly increased (1.4-fold) compared with the controls, but this increase was not observed at days 21 and 28. In the early stage of chondrogenesis (days 4-7), cell proliferation, expressed as the rate of proliferating cell nuclear antigen-positive cells, was increased in mesenchymal (chondroprogenitor) cells but not chondrocytes in the PTH-treated group compared with controls. In addition, gene expression of SOX-9 was up-regulated in the PTH-treated group on day 4 (1.4-fold), and this was accompanied by enhanced expression of pro-alpha1 (II) collagen (1.8-fold). After 14 days, there were no significant differences between groups in either cell proliferation or the expression levels of cartilage differentiation-related genes (SOX-9, pro-alpha1 (II) collagen, pro-alpha1 (X) collagen and osteopontin). These results suggest that intermittent treatment with low-dose rhPTH(1-34) induces a larger cartilaginous callus but does not delay chondrocyte differentiation during fracture healing.

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Keywords

2-month-old Sprague-Dawley rats
 
callus formation
 
cartilage area
 
cartilage differentiation-related genes
 
chondrogenesis
 
Control animals
 
delay chondrocyte differentiation
 
experimental fracture healing
 
expression levels
 
fracture healing
 
intermittent administration
 
larger cartilaginous callus
 
parathyroid hormone
 
PTH-treated group
 
Recent studies
 
recombinant human PTH(1-34)
 
soft callus formation
 
underlying molecular mechanism
 
Unilateral femoral fractures
 
vehicle solution