Endogenous Parathyroid Hormone (PTH) By Activating Hedgehog(Hh) Pathway To Accelerate Fracture Healing

[Objective]:To demonstrate the molecular mechanism of endogenous parathyroid hormone (PTH) promoting fracture healing in adult mice, and the relationship between PTH and Hedgehog (Hh) signaling pathway in fracture healing.[Methods]:Opened mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type (WT) and PTH null (PTH-/-) mice. Callus tissue properties was analyzed at 3、7、10、14 and 21 days post-fracture by radiography、micro-CT、histology、histochemistry and immunohistoche mistry. RNA and proteins were isolated from callus tissues and Hedgehog (Hh) pathway related gene and protein expression levels were evaluated by RT-PCR and Westernblots.[Results]:Bone fracture healig in mice is in cartilage fracture healing callus period at 7、10 and 14 days post-fracture, while is in hard callus phase at 21 days post-fracture.Bone fracture healing process in WT mice is faster than that in KO (PTH-/-) mice; At 7、10 and 14 days post-fracture, expression of Shh GLI1 Smo and ColⅡ in callus of KO mice is significantly downregulated, while GLI3 and PTHR1 expression was significantly up-regulated.[Conclusion]:Compare with WT mice, KO mice fracture healing process is delayed, indicating that endogenous PTH deficiency can lead to fracture healing delayed, that endogenous PTH can promote fracture healing in mice; Endogenous PTH deficiency leads to relatively inhibition of Hh pathway, leading to delayed fracture healing process, that endogenous PTH can activate the Hh pathway, thereby promoting bone fracture healing.