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Magnolin exhibits anti-inflammatory effects on chondrocytes via the NF-κB pathway for attenuating anterior cruciate ligament transection-induced osteoarthritis.
Connect Tissue Res. 2020 Jun 30 [Online ahead of print]CT

Abstract

PURPOSE

This study aimed to investigate whether magnolin (MGL) possesses the capability of suppressing inflammatory responses that can in turn alleviate osteoarthritis (OA).

METHODS

We investigated the effects of MGL on the viability of rat chondrocytes at concentrations of 5 to 100 µM, and selected 10 µM for further study. We elucidated the molecular mechanisms and signaling pathways mediating these effects via RNA sequencing, qRT-PCR, immunofluorescent staining, and Western blotting techniques. Following this, we established an anterior cruciate ligament (ACL) transection-induced OA rat model, and injected MGL into the knee articular cavities to verify the in vivo anti-inflammatory effects of MGL.

RESULTS

We found that MGL could recover the TNF-α-induced upregulation of IL-1β, COX2, ADAMTS-5, and MMP-1/3/13 at the gene/protein level, as well as the downregulation of cartilaginous ECM synthesis. Gene expression profiles of different groups identified 49 common differentially expressed genes (DEGs), which were mainly enriched in the structural constituents of the ribosome, the extracellular space, and inflammatory response. The NF-κB pathway was highly enriched, and the expression levels of DEGs associated with it (Nfkbia, Ptgs2, Rela, Tnfrsf1a, Tradd, Traf2) under TNF-α stimulation were reversed by MGL. Further studies proved that MGL simultaneously suppressed the cell nucleus translocation of p65 and the phosphorylation of IκBα. Moreover, in vivo, MGL suppressed cartilage matrix degradation, inhibited MMP-13 expression, and promoted cartilage matrix construction by upregulating SOX9 synthesis.

CONCLUSION

MGL demonstrated significant anti-inflammatory bioactivity on chondrocytes by suppressing the activation of NF-κB pathway, which in turn exhibited a significant alleviation of OA.

Authors+Show Affiliations

National Innovation and Attracting Talents "111" Base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University , Chongqing, China.National Innovation and Attracting Talents "111" Base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University , Chongqing, China.National Innovation and Attracting Talents "111" Base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University , Chongqing, China.Hubei Engineering Technology Research Center of TCM Processing, College of Pharmacy, Hubei University of Chinese Medicine , Wuhan, China.National Innovation and Attracting Talents "111" Base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University , Chongqing, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32602381

Citation

Xu, Kang, et al. "Magnolin Exhibits Anti-inflammatory Effects On Chondrocytes Via the NF-κB Pathway for Attenuating Anterior Cruciate Ligament Transection-induced Osteoarthritis." Connective Tissue Research, 2020, pp. 1-10.
Xu K, Gao Y, Yang L, et al. Magnolin exhibits anti-inflammatory effects on chondrocytes via the NF-κB pathway for attenuating anterior cruciate ligament transection-induced osteoarthritis. Connect Tissue Res. 2020.
Xu, K., Gao, Y., Yang, L., Liu, Y., & Wang, C. (2020). Magnolin exhibits anti-inflammatory effects on chondrocytes via the NF-κB pathway for attenuating anterior cruciate ligament transection-induced osteoarthritis. Connective Tissue Research, 1-10. https://doi.org/10.1080/03008207.2020.1778679
Xu K, et al. Magnolin Exhibits Anti-inflammatory Effects On Chondrocytes Via the NF-κB Pathway for Attenuating Anterior Cruciate Ligament Transection-induced Osteoarthritis. Connect Tissue Res. 2020 Jun 30;1-10. PubMed PMID: 32602381.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Magnolin exhibits anti-inflammatory effects on chondrocytes via the NF-κB pathway for attenuating anterior cruciate ligament transection-induced osteoarthritis. AU - Xu,Kang, AU - Gao,Yan, AU - Yang,Li, AU - Liu,Yanju, AU - Wang,Chunli, Y1 - 2020/06/30/ PY - 2020/7/1/entrez PY - 2020/7/1/pubmed PY - 2020/7/1/medline KW - Magnolia flos KW - TNF-Α KW - cartilage injury KW - inflammatory responses KW - rna-sequencing SP - 1 EP - 10 JF - Connective tissue research JO - Connect. Tissue Res. N2 - PURPOSE: This study aimed to investigate whether magnolin (MGL) possesses the capability of suppressing inflammatory responses that can in turn alleviate osteoarthritis (OA). METHODS: We investigated the effects of MGL on the viability of rat chondrocytes at concentrations of 5 to 100 µM, and selected 10 µM for further study. We elucidated the molecular mechanisms and signaling pathways mediating these effects via RNA sequencing, qRT-PCR, immunofluorescent staining, and Western blotting techniques. Following this, we established an anterior cruciate ligament (ACL) transection-induced OA rat model, and injected MGL into the knee articular cavities to verify the in vivo anti-inflammatory effects of MGL. RESULTS: We found that MGL could recover the TNF-α-induced upregulation of IL-1β, COX2, ADAMTS-5, and MMP-1/3/13 at the gene/protein level, as well as the downregulation of cartilaginous ECM synthesis. Gene expression profiles of different groups identified 49 common differentially expressed genes (DEGs), which were mainly enriched in the structural constituents of the ribosome, the extracellular space, and inflammatory response. The NF-κB pathway was highly enriched, and the expression levels of DEGs associated with it (Nfkbia, Ptgs2, Rela, Tnfrsf1a, Tradd, Traf2) under TNF-α stimulation were reversed by MGL. Further studies proved that MGL simultaneously suppressed the cell nucleus translocation of p65 and the phosphorylation of IκBα. Moreover, in vivo, MGL suppressed cartilage matrix degradation, inhibited MMP-13 expression, and promoted cartilage matrix construction by upregulating SOX9 synthesis. CONCLUSION: MGL demonstrated significant anti-inflammatory bioactivity on chondrocytes by suppressing the activation of NF-κB pathway, which in turn exhibited a significant alleviation of OA. SN - 1607-8438 UR - https://www.unboundmedicine.com/medline/citation/32602381/Magnolin_exhibits_anti-inflammatory_effects_on_chondrocytes_via_the_NF-κB_pathway_for_attenuating_anterior_cruciate_ligament_transection-induced_osteoarthritis L2 - http://www.tandfonline.com/doi/full/10.1080/03008207.2020.1778679 DB - PRIME DP - Unbound Medicine ER -
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