The protective mechanism of SIRT1 on cartilage through regulation of LEF-1

SIRT1通过调控LEF-1对软骨的保护机制

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作者:Xueyu Hu #, Gangning Feng #, Zhiqiang Meng, Long Ma, Qunhua Jin

Background

Osteoarthritis (OA) is a chronic degenerative disease that suppresses middle-aged and older people worldwide. Silent information regulator 1(SIRT-1) is associated with several age-related diseases, such as cardiovascular diseases, neurodegenerative diseases and tumors, etc. The protective role of SIRT-1 in bone and joint diseases has become increasingly well known.

Conclusion

SRT-1720, as a specific activator of SIRT-1, does increase the protein level of SIRT-1. SIRT-1 may play a protective role in cartilage by regulating the expression of LEF-1 and related inflammatory factors in OA.

Methods

Fresh tibial plateau specimens were collected from 30 patients with knee OA who underwent total knee arthroplasty. According to the

Objective

To explore the relationship between SIRT-1 and its related factors in OA.

Results

In the human cartilage samples, according to the results of Safranin O Fast Green Staining, compared with the mild group, the moderate group and the severe group showed damage cartilage layer structure, the number of chondrocytes decreased, the cell hypertrophic, the cartilage surface discontinuous, and the OARSI grade increased. The severe group had severe cartilage injury and the highest OARSI grade. In the mice cartilage samples, according to immunohistochemical analysis, the protein levels of β-catenin, LEF-1 and MMP-13 in cartilage specimens of model 2 W and model 8 W groups were significantly increased than the sham 2 W and sham 8 W groups. The protein levels of SIRT-1 and Collagen II were significantly decreased (P < 0.05), the results of srt 2 W and srt 8 W groups were between the sham group and the model group. According to immunofluorescence analysis, the protein levels of β-catenin, LEF-1 and MMP-13 in model 2 W and model 8 W groups were significantly increased than sham 2 W and sham 8 W groups. The results of srt 2w and srt 8w groups were between the sham group and the model group. According to the real-time qPCR results: Compared with sham 2 W and sham 8 W groups, the mRNA expression of SIRT-1 in model 2 W and model 8 W groups was significantly decreased, while the mRNA expression of LEF-1 was significantly increased. In contrast, the results of srt 2 W and srt 8 W groups were between the sham group and the model group.

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