Exogenous PTHrP Repairs the Damaged Fracture Healing of PTHrP+/- Mice and Accelerates Fracture Healing of Wild Mice.
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.
Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China. milkyway199@hotmail.com.
Yinhe
Y
Wang
Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 17177, Sweden. xin.fang@ki.se.
Xin
X
Fang
Department of Geriatrics, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China. wangchunglyy@hotmail.com.
Chun
C
Wang
Department of Geriatrics, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China. dingcongzhuglyy@hotmail.com.
Congzhu
C
Ding
Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China. lh2116@126.com.
Hua
H
Lin
Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China. liuanlongglyy@hotmail.com.
Anlong
A
Liu
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. wanglei@sh9hospital.org.
Lei
L
Wang
Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 17177, Sweden. yang.cao@ki.se.|Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro 70182, Sweden. yang.cao@ki.se.
Yang
Y
Cao
D000818:Animals; D015519:Bone Density; D001846:Bone Development / Q000235:genetics; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism; D002146:Bony Callus / Q000187:drug effects / Q000378:metabolism; D002356:Cartilage / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D017102:Fracture Healing / Q000187:drug effects* / Q000235:genetics*; D050723:Fractures, Bone; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics* / Q000494:pharmacology*; D013997:Time Factors
D044162:Parathyroid Hormone-Related Protein
PTHrP+/− mice; bone fracture healing; callus tissue; endogenous; exogenous; parathyroid hormone-related protein (PTHrP)