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Haploinsufficiency of endogenous parathyroid hormone‐related peptide impairs bone fracture healing
Author(s) -
Wang YinHe,
Qiu Yong,
Han XiaoDong,
Xiong Jin,
Chen YiXin,
Shi HongFei,
Karaplis Andrew
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12161
Subject(s) - bone healing , medicine , endocrinology , haploinsufficiency , parathyroid hormone , parathyroid hormone related protein , bone remodeling , runx2 , endogeny , bone resorption , chemistry , femur fracture , alkaline phosphatase , femur , anatomy , surgery , calcium , biochemistry , enzyme , gene , phenotype
Summary Previous studies have demonstrated that endogenous parathyroid hormone‐related peptide ( PTH r P ) plays a central role in the physiological regulation of bone formation. However, it is unclear whether endogenous PTH r P plays an important function in enhancing bone fracture healing. To determine whether endogenous PTH r P haploinsufficiency impaired bone fracture healing, closed mid‐diaphyseal femur fractures were created in 8‐week‐old wild‐type and Pthrp +/− mice. Callus tissue properties were analysed 1, 2 and 4 weeks after fracture by radiography, histology, histochemistry, immunohistochemistry and molecular biology. The size of the calluses was reduced 2 weeks after fracture, and the fracture repairs were poor 4 weeks after fractures, in Pthrp +/− compared with wild‐type mice. Cartilaginous callus areas were reduced 1 week after fracture, but were increased 2 weeks after fracture in Pthrp +/− mice. There was a reduction in the number of ostoblasts, alkaline phosphatase ( ALP )‐positive areas, Type I collagen immunopositive areas, m RNA levels of ALP , Runt‐related transcription factor 2 ( Runx2 ) and Type I collagen, R unx2 and insulin‐like growth factor‐1 protein levels, the number of osteoclasts and the surface in callus tissues in Pthrp +/− compared with wild‐type mice. These results demonstrate that endogenous PTH r P haploinsufficiency impairs the fracture repair process by reducing cartilaginous and bony callus formation, with downregulation of osteoblastic gene and protein expression and a reduction in endochondral bone formation, osteoblastic bone formation and osteoclastic bone resorption. Together, the results indicate that endogenous PTH r P plays an important role in fracture healing.