caa a22 4500 605520526 CHVBK 20210128100735.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00223-015-0041-2 doi (NATIONALLICENCE)springer-10.1007/s00223-015-0041-2 Exogenous Parathyroid Hormone-Related Peptide Promotes Fracture Healing in Lepr(−/−) Mice [Elektronische Daten] [Anlong Liu, Yishan Li, Yinhe Wang, Li Liu, Hongfei Shi, Yong Qiu] 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 2weeks, callus tissue properties were analyzed by radiography, micro-computed tomography, histology, histochemistry, immunohistochemistry, and molecular biology techniques. At 2weeks 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. Springer Science+Business Media New York, 2015 Bone fracture healing nationallicence Lepr(−/−) nationallicence PTHrP nationallicence Subcutaneous injection nationallicence Mouse model nationallicence Liu Anlong Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China aut Li Yishan Department of International Training, PLA University of Science and Technology, 210007, Nanjing, Jiangsu, China aut Wang Yinhe Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China aut Liu Li Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China aut Shi Hongfei Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China aut Qiu Yong Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China aut Calcified Tissue International Springer US; http://www.springer-ny.com 97/6(2015-12-01), 581-591 0171-967X 97:6<581 2015 97 223 https://doi.org/10.1007/s00223-015-0041-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-015-0041-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Liu Anlong Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Li Yishan Department of International Training, PLA University of Science and Technology, 210007, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Wang Yinhe Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Liu Li Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Shi Hongfei Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China aut NATIONALLICENCE 700 1- Qiu Yong Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 97/6(2015-12-01), 581-591 0171-967X 97:6<581 2015 97 223