title: Exogenous Parathyroid Hormone-Related Peptide Promotes Fracture Healing in Lepr(-/-) Mice.
abstract: Diabetic osteoporosis continues to surge worldwide, increasing the risk of fracture. We have previously demonstrated that haploinsufficiency of endogenous parathyroid hormone-related peptide (PTHrP) impairs fracture healing. However, whether an exogenous supply of PTHrP can repair bone damage and accelerate fracture healing remains unclear. This study aimed to assess the efficacy and safety of PTHrP in healing fractures. Standardized mid-diaphyseal femur fractures were generated in 12-week-old wild-type and leptin receptor null Lepr(-/-) mice. After administration of PTHrP for 2 weeks, callus tissue properties were analyzed by radiography, micro-computed tomography, histology, histochemistry, immunohistochemistry, and molecular biology techniques. At 2 weeks post-fracture, cartilaginous callus areas were reduced, while total callus and bony callus areas were increased in PTHrP-treated Lepr(-/-) animals and control wild-type mice, compared with vehicle-treated Lepr(-/-) mice. The following parameters were enhanced both in Lepr(-/-) mice after treatment with PTHrP and vehicle-treated wild-type animals, compared with vehicle-treated Lepr(-/-) mice: osteoblast numbers; tissue alkaline phosphatase (ALP) and Type I collagen immunopositive areas; mRNA levels of ALP, Type I collagen, osteoprotegerin, and receptor activator for nuclear factor-κ B ligand; protein levels of Runt-related transcription factor 2 and insulin-like growth factor-1; and the number and surface of osteoclasts. In conclusion, exogenous PTHrP by subcutaneous injection promotes fracture repair in Lepr(-/-) mice by increasing callus formation and accelerating cell transformation: upregulated osteoblastic gene and protein expression, increased endochondral bone formation, osteoblastic bone formation, and osteoclastic bone resorption. However, complete repair was not obtained in PTHrP-treated Lepr(-/-) mice as in control wild-type animals.
authors: Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China.
authors: Anlong
authors: A
authors: Liu
authors: Department of International Training, PLA University of Science and Technology, Nanjing, 210007, Jiangsu, China.
authors: Yishan
authors: Y
authors: Li
authors: Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. wangyinhesci@126.com.
authors: Yinhe
authors: Y
authors: Wang
authors: Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China.
authors: Li
authors: L
authors: Liu
authors: Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China.
authors: Hongfei
authors: H
authors: Shi
authors: Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. scoliosis2002@sina.com.
authors: Yong
authors: Y
authors: Qiu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001862:Bone Resorption / Q000378:metabolism; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D017102:Fracture Healing / Q000187:drug effects*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000187:drug effects; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D044162:Parathyroid Hormone-Related Protein; D054411:Receptors, Leptin; C515447:leptin receptor, mouse
keywords: Bone fracture healing; Lepr(−/−); Mouse model; PTHrP; Subcutaneous injection