Quercetin mediates TSC2-RHEB-mTOR pathway to regulate chondrocytes autophagy in knee osteoarthritis.

Abstract

OBJECTIVE:

This study aimed to explore the specific molecular mechanism of the therapeutic effect of quercetin in knee osteoarthritis (KOA).

METHODS:

The KOA rat model was constructed by excising the medial meniscus and transecting the anterior meniscus. Joint injuries in rats were determined by Hematoxylin-Eosin (H&E) and Safranin O staining. The severity of KOA was then assessed according to the Osteoarthritis Research Society International (OARSI). The expressions of TSC2 and LC2B in joint tissue were measured by immunohistochemistry. Besides, chondrocytes treated with 10 ng/ml IL-1β were used to construct a chondrocyte arthritis model, while those treated with 4 or 8 μM quercetin were served as treatment groups. MTT, flow cytometry and toluidine blue staining were used to detect cell viability, apoptosis and mucopolysaccharide synthesis, respectively. qRT-PCR or Western blot was performed to determine the expressions of MMP-13, collagen II, Aggrecan, TSC2, RHEB, mTOR, p-mTOR, ULK1, p-ULK1, LC3B-I, LC3B-II and P62 in chondrocytes.

RESULTS:

Quercetin alleviated the joint injury and suppressed the increase in MMP-13 expression and the decreases in collagen II and Aggrecan expressions in KOA rats. In addition, quercetin suppressed RHEB, p-mTOR, p-ULK1 and P62 expressions but promoted TSC2 and LC3BII expressions in KOA rats. Furthermore, quercetin could relieve the decrease of cell viability and the increase of apoptosis that induced by IL-1β, and promote the synthesis of IL-1β-inhibited mucopolysaccharide in chondrocytes. Nevertheless, siTSC2 partially offset the therapeutic effects of quercetin in chondrocytes.

CONCLUSION:

Quercetin alleviated KOA by mediating the TSC2-RHBE-mTOR signaling pathway.

• Authors: Shuaijie Lv, Xiaojian Wang, Shuaijie Jin, Shaoning Shen, Rui Wang, Peijian Tong
• Journal: Gene (Gene) Vol. 820 Pg. 146209 (Apr 30 2022) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 35093450 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Glycosaminoglycans
• Interleukin-1beta
• Ras Homolog Enriched in Brain Protein
• Rheb protein, rat
• Tsc2 protein, rat
• Tuberous Sclerosis Complex 2 Protein
• Collagen
• Quercetin
• mTOR protein, rat
• TOR Serine-Threonine Kinases
• Matrix Metalloproteinase 13

Topics

• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Chondrocytes (drug effects, metabolism)
• Collagen (metabolism)
• Disease Models, Animal
• Gene Expression Regulation
• Glycosaminoglycans (metabolism)
• Inflammation (metabolism)
• Interleukin-1beta (metabolism)
• Male
• Matrix Metalloproteinase 13 (metabolism)
• Osteoarthritis, Knee (drug therapy, metabolism)
• Quercetin (pharmacology)
• Ras Homolog Enriched in Brain Protein (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Tuberous Sclerosis Complex 2 Protein (metabolism)