Knockdown of Ggps1 in chondrocyte expedites fracture healing by accelerating the progression of endochondral ossification in mice.
J Bone Miner Metab
; 36(2): 133-147, 2018 Mar.
Article
en En
| MEDLINE
| ID: mdl-28357594
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-CreERT2 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-CreERT2 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Osteogénesis
/
Curación de Fractura
/
Condrocitos
/
Farnesiltransferasa
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Técnicas de Silenciamiento del Gen
/
Complejos Multienzimáticos
Límite:
Animals
Idioma:
En
Revista:
J Bone Miner Metab
Asunto de la revista:
METABOLISMO
Año:
2018
Tipo del documento:
Article