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Int. J. Mol. Sci. 2017, 18(2), 337; doi:10.3390/ijms18020337

Exogenous PTHrP Repairs the Damaged Fracture Healing of PTHrP+/− Mice and Accelerates Fracture Healing of Wild Mice

1
Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
2
Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 17177, Sweden
3
Department of Geriatrics, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
4
Department of Oral & Maxillofacial-Head & Neck Oncology, The Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China
5
Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro 70182, Sweden
*
Authors to whom correspondence should be addressed.
Academic Editor: Charles J. Malemud
Received: 18 December 2016 / Revised: 29 January 2017 / Accepted: 1 February 2017 / Published: 6 February 2017
(This article belongs to the Special Issue Musculoskeletal Diseases Therapy)
View Full-Text   |   Download PDF [4880 KB, uploaded 6 February 2017]   |  

Abstract

Bone fracture healing is a complicated physiological regenerative process initiated in response to injury and is similar to bone development. To demonstrate whether an exogenous supply of parathyroid hormone–related protein (PTHrP) helps in bone fracture healing, closed mid-diaphyseal femur fractures were created and stabilized with intramedullary pins in eight-week-old wild-type (WT) PTHrP+/+ and PTHrP+/− mice. After administering PTHrP for two weeks, callus tissue properties were analyzed at one, two, and four weeks post-fracture (PF) by various methods. Bone formation–related genes and protein expression levels were evaluated by real-time reverse transcriptase–polymerase chain reaction and Western blots. At two weeks PF, mineral density of callus, bony callus areas, mRNA levels of alkaline phosphatase (ALP), type I collagen, Runt-related transcription factor 2 (Runx-2), and protein levels of Runx-2 and insulin-like growth factor-1 decreased in PTHrP+/− mice compared with WT mice. At four weeks PF, total collagen-positive bony callus areas, osteoblast number, ALP-positive areas, and type I collagen-positive areas all decreased in PTHrP+/− mice. At both two and four weeks PF, tartrate-resistant acid phosphatase–positive osteoclast number and surface decreased a little in PTHrP+/− mice. The study indicates that exogenous PTHrP provided by subcutaneous injection could redress impaired bone fracture healing, leading to mutation of activated PTHrP by influencing callus areas, endochondral bone formation, osteoblastic bone formation, and bone turnover. View Full-Text
Keywords: bone fracture healing; parathyroid hormone-related protein (PTHrP); PTHrP+/− mice; exogenous; endogenous; callus tissue bone fracture healing; parathyroid hormone-related protein (PTHrP); PTHrP+/− mice; exogenous; endogenous; callus tissue
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MDPI and ACS Style

Wang, Y.; Fang, X.; Wang, C.; Ding, C.; Lin, H.; Liu, A.; Wang, L.; Cao, Y. Exogenous PTHrP Repairs the Damaged Fracture Healing of PTHrP+/− Mice and Accelerates Fracture Healing of Wild Mice. Int. J. Mol. Sci. 2017, 18, 337.

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