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. 2022 May 30;23(1):513.
doi: 10.1186/s12891-022-05469-5.

The mechanism by which enoxaparin sodium-high-viscosity bone cement reduces thrombosis by regulating CD40 expression in endothelial cells

Linchao Sang  1 , Kangning Hao  1 , Luobin Ding  1 , Xiaoyu Shen  1 , Hui Sun  2 , Dehao Fu  3 , Xiangbei Qi  4
Affiliations

The mechanism by which enoxaparin sodium-high-viscosity bone cement reduces thrombosis by regulating CD40 expression in endothelial cells

Linchao Sang et al. BMC Musculoskelet Disord. .

Abstract

Objective: PMMA bone cement leads to the development of local thrombi. Our study found that ES-PMMA bone cement, a novel material, can reduce local thrombosis. We used a simple and reproducible animal model to confirm the reduction in local thrombosis and preliminarily explored the associated molecular mechanism.

Methods: New Zealand rabbits, which were used to model thrombosis using extracorporeal carotid artery shunts, were divided into the following three groups, with 10 rabbits in each group: the sham group, PMMA group and ES-PMMA group. Four hours after modelling, experimental samples were collected, and the degree of thrombosis was compared between the groups. The expression of thrombomodulin in endothelial cells was quantified in vascular tissues samples.

Results: Thrombosis was observed in the PMMA group and ES-PMMA group but not in the sham group. The thrombosis weight was 0.00732 ± 0.00089 g/cm in the PMMA group and 0.00554 ± 0.00077 g/cm in the ES-PMMA group (P < 0.001). Quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting revealed that the expression of CD40, which can regulate thrombosis in vascular endothelial cells, was significantly lower in the ES-PMMA group than in the PMMA group.

Conclusion: Compared with PMMA bone cement, ES-PMMA bone cement can reduce local thrombosis by decreasing the expression of the thrombus-associated regulatory protein CD40 in vascular endothelial cells.

Keywords: Bone cement; CD40; Endothelial cells; Enoxaparin sodium; Thrombosis.

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Conflict of interest statement

This material has not been published and is not under consideration elsewhere. The authors declare that they have no competing interests. All authors have read and contributed to the submitted manuscript, and there is no conflict of interest among the authors.

Figures

Fig. 1
Fig. 1
a Enoxaparin sodium (ES) and high-viscosity bone cement powder samples. b The extracorporeal shunt and prepared silk thread with bone cement. c The exposed arteriovenous vessels of New Zealand rabbits. d Establishment of the animal model. e Blood vessels contacting thread covered with bone cement. f: Intravascular bone cement-induced thrombus samples (the original images are presented in Supplementary Fig. 1)
Fig. 2
Fig. 2
a PMMA. There were many gaps between the bone cement particles. b ES-PMMA. The surface of the bone cement particles was covered with a syrup-like substance, which was considered the attached enoxaparin (the original images are presented in Supplementary Fig. 2)
Fig. 3
Fig. 3
mRNA expression levels of CD31, CD40, CD62p, CD106, endothelin, and thrombomodulin showing that CD62p and CD40 expression was decreased in the M group compared with the Con group (P < 0.01) and that CD40 mRNA expression was significantly decreased in the FS group compared with the Con group (P < 0.001. (the raw data and image are presented in Supplementary Fig. 3)
Fig. 4
Fig. 4
Protein expression levels of CD31, CD40, CD62p, CD106, endothelin, and thrombomodulin. The expression levels of CD31 and CD40 were decreased in the M group compared with the Con group (P < 0.05), and the expression levels of CD40 were significantly decreased in the FS group compared with the Con group (p < 0.01) (the original images were cropped to improve the clarity and conciseness of the presentation; the original blots/gels are presented in Supplementary Fig. 4)
Fig. 5
Fig. 5
The fluorescence intensity of CD40 in vascular endothelial cells was significantly lower in the M group and FS group than in the Con group (the original images are presented in Supplementary Fig. 5)
See this image and copyright information in PMC

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