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Published on: January 12, 2024
L-Glutamine alleviates osteoarthritis by regulating lncRNA-NKILA expression through the TGF-β1/SMAD2/3 signalling
Xiao Ma1, Dechao Cai1, Yakun Zhu2
1Department of Orthopedics, The Second Hospital of Anhui Medical University, Hefei, China.
Abstract:
Osteoarthritis (OA) is a heterogeneous condition characterized by cartilage degradation, subchondral sclerosis, and osteophyte formation, and accompanied by the generation of pro-inflammatory mediators and degradation of extracellular matrix. The current treatment for early OA is focused on the relief of symptoms, such as pain, but this treatment cannot delay the pathological process. L-Glutamine (L-Gln), which has anti-inflammatory and anti-apoptotic effects, is the most abundant amino acid in human blood. However, its role in OA has not been systematically studied. Therefore, the objective of this work was to explore the therapeutic effect and molecular mechanism of L-Gln on OA. In vitro, we found that L-Gln could up-regulate the expression of the long non-coding RNA NKILA, which is regulated by the transforming growth factor-β1/SMAD2/3 pathway, and inhibit the activity of nuclear factor-κB, thereby decreasing the expression of nitric oxide synthase, cyclooxygenase-2, and matrix metalloproteinase-13 (MMP-13). This led to a reduction in the generation of nitrous oxide, prostaglandin E-2, tumour necrosis factor-α, and degradation of the extracellular matrix (i.e. aggrecan and collagen II) in rat OA chondrocytes. Moreover, intragastric administration of L-Gln reduced the degradation of cartilage tissue and expression of MMP-13 in a rat OA model. L-Gln also relieved the clinical symptoms in some patients with early knee joint OA. These findings highlight that L-Gln is a potential therapeutic drug to delay the occurrence and development of OA.
Insights
L-Glutamine (L-Gln) may treat osteoarthritis (OA) by reducing inflammation and cartilage breakdown. This abundant amino acid shows promise in delaying OA progression and alleviating knee joint pain in patients.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Osteoarthritis (OA) involves cartilage degradation and inflammation, with current treatments only managing symptoms.
- L-Glutamine (L-Gln), an abundant amino acid, possesses anti-inflammatory and anti-apoptotic properties.
- The therapeutic role of L-Gln in OA has not been extensively studied.
Purpose of the Study:
- To investigate the therapeutic potential of L-Gln in osteoarthritis.
- To elucidate the molecular mechanisms underlying L-Gln's effects on OA.
Main Methods:
- In vitro studies using rat OA chondrocytes to assess L-Gln's effects on gene expression and inflammatory markers.
- In vivo studies using a rat OA model to evaluate L-Gln's impact on cartilage degradation.
- Clinical observation of patients with early knee joint OA receiving L-Gln.
Main Results:
- L-Gln up-regulated long non-coding RNA NKILA expression via the TGF-β1/SMAD2/3 pathway.
- L-Gln inhibited nuclear factor-κB activity, reducing nitric oxide synthase, cyclooxygenase-2, and MMP-13 expression.
- L-Gln decreased inflammatory mediators (nitrous oxide, prostaglandin E-2, TNF-α) and extracellular matrix degradation (aggrecan, collagen II) in vitro and in vivo.
- L-Gln administration reduced cartilage degradation and MMP-13 expression in a rat OA model.
- L-Gln provided clinical symptom relief in some patients with early knee OA.
Conclusions:
- L-Glutamine demonstrates significant therapeutic effects against osteoarthritis.
- L-Gln acts by modulating the NKILA/NF-κB pathway, thereby reducing inflammation and matrix degradation.
- L-Gln presents a potential therapeutic strategy to delay osteoarthritis onset and progression.
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