Bone morphogenetic protein 9 stimulates callus formation in osteoporotic rats during fracture healing

Wang,Xing; Huang,Jun; Huang,Fan; Zong,Jian‑Chun; Tang,Xi; Liu,Yang; Zhang,Qiong‑Fang; Wang,Yang; Chen,Liang; Yin,Liang‑Jun; He,Bai‑Cheng; Deng,Zhong‑Liang

doi:10.3892/mmr.2017.6302

Bone morphogenetic protein 9 stimulates callus formation in osteoporotic rats during fracture healing

Authors:
- Xing Wang
- Jun Huang
- Fan Huang
- Jian‑Chun Zong
- Xi Tang
- Yang Liu
- Qiong‑Fang Zhang
- Yang Wang
- Liang Chen
- Liang‑Jun Yin
- Bai‑Cheng He
- Zhong‑Liang Deng
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Affiliations: Department of Orthopaedic Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400010, P.R. China, Center for Musculoskeletal Surgery, Charité‑Universitätsmedizin, D‑13353 Berlin, Germany, Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China
Published online on: March 9, 2017 https://doi.org/10.3892/mmr.2017.6302
Pages: 2537-2545
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fracture healing involves the coordinated actions of multiple cytokines. Bone morphogenetic protein 9 (BMP9) is an important factor in bone formation. The present study aimed to investigate the osteogenic potential of bone marrow stem cells (BMSCs) in response to adenoviral (Ad)BMP9, and the early fracture repair properties of AdBMP9 in surgically‑created fractures in osteoporotic rats. Alkaline phosphatase (ALP) activity was assayed and matrix mineralization was examined by Alizarin Red S staining. mRNA and protein expression levels of BMP9, runt‑related transcription factor 2 (RUNX2) and type 1 collagen (COL‑1) were detected in vitro and in vivo. Femoral bone mineral density was assessed for osteoporosis in ovariectomized rats. An open femora fracture was subsequently created, and gelatin sponges containing AdBMP9 were implanted. The femora were harvested for radiographical, micro‑computed tomography, biomechanical and histological analysis 4 weeks later. BMP9 successfully increased ALP activity and induced mineralized nodule formation in BMSCs. BMP9 in gelatin sponges demonstrated marked effects on microstructural parameters and the biomechanical strength of bone callus. In addition, it upregulated the expression levels of RUNX2 and COL‑1. AdBMP9 in gelatin sponges significantly mediated callus formation, and increased bone mass and strength in osteoporotic rats with femora fractures. The results of the present study suggested that BMP9 enhanced callus formation and maintained early mechanical stability during fracture healing in osteoporotic rats, implicating it as a potential novel therapeutic target for fracture healing.

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