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Exogenous PTHrP Repairs the Damaged Fracture Healing of PTHrP plus /- Mice and Accelerates Fracture Healing of Wild Mice
Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Geriatrics, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Department of Geriatrics, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
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2017 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 18, no 2, 337Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
MDPI AG , 2017. Vol. 18, no 2, 337
Keyword [en]
bone fracture healing, parathyroid hormone-related protein (PTHrP), PTHrP plus /- mice, exogenous, endogenous, callus tissue
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-57003DOI: 10.3390/ijms18020337ISI: 000395457700105Scopus ID: 2-s2.0-85011957139OAI: oai:DiVA.org:oru-57003DiVA: diva2:1087915
Note

Funding Agencies:

National Natural Science Foundation of China  81271997  81401793

Medical Science and Technology Development Foundation, Department of Health of Nanjing City  ZKX10007

Postdoctoral Science Foundation of China  20100481130

Medical Key Personnel Program of Jiangsu Province, China  RC2011150

Available from: 2017-04-10 Created: 2017-04-10 Last updated: 2017-04-10Bibliographically approved

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