AEG-1 Deletion Promotes Cartilage Repair and Modulates Bone Remodeling-related Cytokines Via TLR4/MyD88/NF-κB Inhibition in Ovariectomized Rats with Osteoporosis

Overview

Journal Ann Transl Med

Publisher AME Publishing Company

Date 2020 Nov 19

PMID 33209878

Citations 3

Authors

Yuan Zhang

Qing Zhao

Affiliations

Soon will be listed here.

Abstract

Background: Osteoporosis is a systemic skeletal disorder that can impact a variety of bones throughout the body. Astrocyte-elevated gene-1 (AEG-1) is involved in multiple pro-tumorigenic functions and participates in various inflammatory reactions. However, whether it has an impact on osteoporosis-related cartilage repair and bone remodeling remains unknown.

Methods: We utilized an ovariectomy mouse model with AEG-1 deletion to investigate the role of AEG-1 in osteoporosis. The mRNA level of AEG-1 was detected by RT-PCR, bone markers, bone volume/total volume (BV/TV), trabecular bone surface/bone volume (BSA/BV) and trabecular bone thickness (Tb. Th) were detected by micro computed tomography (µCT), bone injury was observed by HE and alcian blue staining. The contents of IL-6, IL-17, iNOS and IL-10 in peripheral blood of the three groups were detected by ELISA. The expression of OSX, coi1a1, OC, TLR4, MyD88 and NF-κB were detected by Western Blot.

Results: µCT revealed increased bone volume in the AEG-1 knockout (KO) ovariectomy (OVX) group compared to the wildtype (WT) OVX group 4 weeks after surgery, indicating restored bone formation after AEG-1 deletion. Flow sorting revealed that AEG-1 deletion inhibited the production of inflammatory factors. Western blot demonstrated activation of the TLR4/MyD88/NF-κB pathway after LPS exposure, which was reduced by AEG-1 deletion. AEG-1 deletion also improved lipopolysaccharide (LPS) induced adverse reactions.

Conclusions: Taken together, these findings indicate that AEG-1 deletion improves cartilage repair and bone remodeling during osteoporosis, which may partly occur through the inhibition of the TLR4/MyD88/NF-κB signaling pathway.

Citing Articles

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High-mobility group box chromosomal protein-1 deletion alleviates osteoporosis in OVX rat model via suppressing the osteoclastogenesis and inflammation.

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