Exogenous Parathyroid Hormone-Related Peptide Promotes Fracture Healing in Lepr(−/−) Mice

Verfasser / Beitragende:
[Anlong Liu, Yishan Li, Yinhe Wang, Li Liu, Hongfei Shi, Yong Qiu]
Ort, Verlag, Jahr:
2015
Enthalten in:
Calcified Tissue International, 97/6(2015-12-01), 581-591
Format:
Artikel (online)
ID: 605520526
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024 7 0 |a 10.1007/s00223-015-0041-2  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00223-015-0041-2 
245 0 0 |a Exogenous Parathyroid Hormone-Related Peptide Promotes Fracture Healing in Lepr(−/−) Mice  |h [Elektronische Daten]  |c [Anlong Liu, Yishan Li, Yinhe Wang, Li Liu, Hongfei Shi, Yong Qiu] 
520 3 |a 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. 
540 |a Springer Science+Business Media New York, 2015 
690 7 |a Bone fracture healing  |2 nationallicence 
690 7 |a Lepr(−/−)  |2 nationallicence 
690 7 |a PTHrP  |2 nationallicence 
690 7 |a Subcutaneous injection  |2 nationallicence 
690 7 |a Mouse model  |2 nationallicence 
700 1 |a Liu  |D Anlong  |u Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China  |4 aut 
700 1 |a Li  |D Yishan  |u Department of International Training, PLA University of Science and Technology, 210007, Nanjing, Jiangsu, China  |4 aut 
700 1 |a Wang  |D Yinhe  |u Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China  |4 aut 
700 1 |a Liu  |D Li  |u Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China  |4 aut 
700 1 |a Shi  |D Hongfei  |u Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China  |4 aut 
700 1 |a Qiu  |D Yong  |u Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China  |4 aut 
773 0 |t Calcified Tissue International  |d Springer US; http://www.springer-ny.com  |g 97/6(2015-12-01), 581-591  |x 0171-967X  |q 97:6<581  |1 2015  |2 97  |o 223 
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950 |B NATIONALLICENCE  |P 700  |E 1-  |a Liu  |D Anlong  |u Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Li  |D Yishan  |u Department of International Training, PLA University of Science and Technology, 210007, Nanjing, Jiangsu, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Yinhe  |u Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Liu  |D Li  |u Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Shi  |D Hongfei  |u Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Qiu  |D Yong  |u Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, Jiangsu, China  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Calcified Tissue International  |d Springer US; http://www.springer-ny.com  |g 97/6(2015-12-01), 581-591  |x 0171-967X  |q 97:6<581  |1 2015  |2 97  |o 223