Effect Of Both Endogenous And Exogenous PTH On Mice Bone Fracture Healing

【Objective】:To demonstrate whether both endogenous and exogenous PTH stimulate bone fracture healing.【Mathods】:Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type (WT) and PTH null (PTH-/-) mice. Mice received daily injections of vehicle (V) or of PTH1-34 (80μg/kg) for 1-4 weeks post-fracture, and callus tissue properties was analyzed at 1, 2 and 4 weeks post-fracture by radiography, micro-CT, histology, histochemistry and immunohistochemistry. RNA and proteins were isolated from callus tissues and bone formation related gene and protein expression levels were evaluated by RT-PCR and Western blots.【Results】:At 1 week post-fracture, cartilaginous callus areas were reduced in V-treated and PTH-treated PTH-/- mice compared to V-treated and PTH-treated WT mice respectively, but were increased in both PTH-treated WT and PTH-/- mice compared to V-treated WT and PTH-/- mice respectively. In contrast, at 2 weeks post-fracture, remnant cartilaginous callus areas were increased in V-treated and PTH-treated PTH-/- mice compared to V-treated and PTH-treated WT mice respectively and were reduced in PTH-treated WT and PTH-/- mice compared to V-treated WT and PTH-/- respectively. As well, at 2 weeks post-fracture, the mineral density in callus and bony callus areas, the mRNA levels of ALP, type I collagen, and the protein levels of Cbfa1 and IGF-I were reduced in V-treated and PTH-treated PTH-/- mice compared to V-treated and PTH-treated WT mice respectively and were increased in PTH-treated WT and PTH-/- mice compared to V-treated WT and PTH-treated PTH-/- mice respectively. At 4 weeks post-fracture, total collagen positive bony callus areas, osteoblast number, ALP positive areas and type I collagen positive areas were all reduced in V-treated and PTH-treated PTH-/- mice compared to V-treated and PTH-treated WT mice respectively and were increased in PTH-treated WT and PTH-/- mice compared to V-treated WT and PTH-/- mice respectively. At 2 and 4 weeks post-fracture, TRAP positive osteoclast number and surface were also reduced in V-treated and PTH-treated PTH-/- mice compared to V-treated and PTH-treated WT mice respectively,but were increased in PTH-treated WT and PTH-/- mice compared to V-treated WT and PTH-/- mice respectively.【Conclusion】:These results indicate that both endogenous and exogenous PTH enhance bone fracture healing by increasing callus areas, endochondral bone formation and osteoblastic bone formation.