SMAD7 prevents heterotopic ossification by regulating endothelial-mesenchymal transition after Achilles tendon imjury
10.3969/j.issn.2095-4344.2017.08.006
- VernacularTitle:SMAD7调控内皮间质转化可预防跟腱损伤后的异位骨化
- Author:
Chi ZHANG
;
Fang JI
- From:
Chinese Journal of Tissue Engineering Research
2017;21(8):1178-1185
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: The endothelial-mesenchymal transition is known to play a central role in the pathological process of heterotopic ossification. OBJECTIVE: To verify the inhibitory effect of SMAD7 on endothelial-mesenchymal transition such as myofibroblast transformation and to explore whether it is a potential target for heterotopic ossification.METHODS: A lentivirus overexpressing SMAD7 was contructed and the optimal titre and transfection efficiency in rat aortic endothelial cells were determined. The lentivirus was then injected into a rat model of Achilles tendon injury, while the controls were given the injection of normal saline. Expressions of endothelial and mesenchymal markers at the injured site were analyzed by quantitative PCR and western blot assay. The heterotopic ossification was observed radiologically and histologically.RESULTS AND CONCLUSION: Local injection of SMAD7-delivering lentivirus resulted in an upregulation of CD31 and VE-cadherin, and a downregulation of N-cadherin and vimentin, suggesting that the endothelial-mesenchymal transition is blocked due to local SMAD7 overexpression. The inhibitory effect became more evident at 10 weeks than at 6 weeks after modeling. Radiology and histological staining further confirmed that the ossified structures in the tendon tissue disappeared after injection of SMAD7-delivering lentivirus, as opposed to the control group. These data suggest that local overexpression of SMAD7 can prevent postoperative heterotopic ossification with no effect on wound healing.
