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29.03.2017 | Original Article

Knockdown of Ggps1 in chondrocyte expedites fracture healing by accelerating the progression of endochondral ossification in mice

verfasst von: Bingyang Dai, Qiangqiang Li, Xiaoxiao Song, Yuxiang Ge, Jing Wu, Kaijia Zhang, Chao Wang, Yifeng Zhang, Huajian Teng, Chaojun Li, Qing Jiang

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 2/2018

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Abstract

Bone fracture healing is achieved through the proliferation and differentiation of stem cells, while bone marrow stem cells (BMSCs) contribute to endochondral ossification. During fracture healing, mesenchymal progenitor cells first form a cartilaginous blastema that becomes vascularized to recruit precursor cells of osteoblasts through the bone morphogenetic protein 2 (Bmp2)/Smad-dependent Runx2 pathway. Statins deplete geranylgeranyl diphosphate (GGPP), which participates in the regulation of BMSCs differentiation, through the inhibition of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, leading to impaired protein geranylgeranylation, which strongly impacts the bone synthesis induced by Bmp2. Accordingly, we would like to investigate the role of geranylgeranyl diphosphate synthase 1 (Ggps1) in bone fracture via endochondral ossification in mice. We used a Cre-loxP system, namely the tamoxifen-inducible Collagen 2-CreER^T2 Ggps1 ^fl/fl, to eliminate specifically the Ggps1 activity in chondrocytes of 8–10-week-old mice. We found that the endochondral bone formation, calcification and vasculogenesis of the bony callus were accelerated in fractures in Ggps1^−/−mice. Together, the results of this study confirm that the specific deletion of Ggps1, using the Collagen 2-CreER^T2 mice, will accelerate the fracture healing process by activating the Bmp2/Smad-dependent Runx2 pathway. In addition, we managed to improve the fracture healing process by inhibiting the Ggps1 activity and its related products with statin drugs.

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Titel: Knockdown of Ggps1 in chondrocyte expedites fracture healing by accelerating the progression of endochondral ossification in mice
verfasst von: Bingyang Dai
Qiangqiang Li
Xiaoxiao Song
Yuxiang Ge
Jing Wu
Kaijia Zhang
Chao Wang
Yifeng Zhang
Huajian Teng
Chaojun Li
Qing Jiang
Publikationsdatum: 29.03.2017
Verlag: Springer Japan
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 2/2018
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-017-0824-9

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