Maresin-1 suppresses IL-1β-induced MMP-13 secretion by activating the PI3K/AKT pathway and inhibiting the NF-κB pathway in synovioblasts of an osteoarthritis rat model with treadmill exercise

Lu, Jinghan; Feng, Xinyuan; Zhang, He; Wei, Yuansong; Yang, Yue; You, Tian; Bai, Lan

doi:10.1080/03008207.2020.1780218

Cited by 39 publications

(31 citation statements)

References 38 publications

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“…In degenerative response, ECM degradation cannot be separated from matrix metalloproteinase such as MMP1, MMP3, and MMP13 [ 7 ]. So we choose MMP13 to evaluate degrading enzyme activity, and the results were identified that LY294002 upregulated MMP13 expression and IGF-1 downregulated MMP13 expression which consistent with the findings of Lu et al that in the osteoarthritis rat model via activating P13K/AKT, MMP13 secretion was suppressed [ 32 ]. What is more, Liu et al also argued MMP3 can be decreased in the treatment of IGF-1 [ 21 ].…”

Section: Discussionsupporting

confidence: 77%

Role of PI3K/AKT Signaling Pathway in Nucleus Pulposus Cells

Xiao¹,

Teng

Xu³

et al. 2021

BioMed Research International

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Objective. To investigate the role of PI3K/AKT signaling pathway in nucleus pulposus (NP) cells. Methods. Nucleus pulposus (NP) cells were isolated from SD rat, and thereafter, passage three (P3) NP cells were divided into the following experimental groups: control, PI3K/AKT agonist IGF-1 (25 ng/ml, 50 ng/ml, and 100 ng/ml), and PI3K/AKT inhibitor LY294002 (5 μM, 10 μM, and 20 μM). Flow cytometry and BrdU cell proliferation assays were performed to assess apoptosis and the proliferation rate of NP cells. Western blot analysis was performed to examine the protein expression level of Col II, Col X, Aggrecan, and MMP13. Results. PI3K/AKT inhibitor LY294002 increased the rate of apoptosis in NP cells when compared to the control and decreased the proliferation rate when compared to control. Moreover, LY294002 decreased the protein expression level of Col-II and Aggrecan in NP cells. At the same time, LY294002 increased the protein expression level of MMP13 and Col-X in NP cells. Through activating PI3K/AKT, IGF-1 increased the proliferation rate when compared to control and decreased the rate of apoptosis when compared to control. Additionally, IGF-1 decreased the protein expression level of MMP13 and Col-X and increased Col-II and Aggrecan in NP cells. Conclusion. The inhibition of PI3K/AKT signaling pathway accelerated the apoptosis of NP cells and facilitated the extracellular matrix degradation. However, the activation of PI3K/AKT pathway partly prevented the NP cell from apoptosis and promoted their proliferation. Meanwhile, its activation also delayed the loss of extracellular matrix.

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Section: Discussionsupporting

confidence: 77%

Role of PI3K/AKT Signaling Pathway in Nucleus Pulposus Cells

Xiao¹,

Teng

Xu³

et al. 2021

BioMed Research International

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“…The aging model was divided into four groups according to age ( n = 6 per group): 1 month old (1 M), 6 months old (6 M), 12 months old (12 M), and 18 months old (18 M). The MIA model (induced by the injection of 40 µl saline with or without 0.2 mg MIA into the intra‐articular cavity of 8‐week‐old SD rats after anesthetization with isoflurane as previously described) (Lu et al, 2020; Udo et al, 2016; H. Zhang et al, 2019) was also divided into four groups ( n = 6 per group) according to MIA treatment time: saline control (Ctrl), MIA treatment for 1 week (1 W), MIA treatment for 2 weeks (2 W), and MIA treatment for 3 weeks (3 W).…”

Section: Methodsmentioning

confidence: 99%

JUNB‐FBXO21‐ERK axis promotes cartilage degeneration in osteoarthritis by inhibiting autophagy

Lin

Jiang²,

Zhang

et al. 2021

Aging Cell

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Osteoarthritis (OA) is a heterogeneous disease that is extremely hard to cure owing to its complex regulation network of pathogenesis, especially cartilage degeneration. FBXO21 is a subunit of ubiquitin E3 ligases that degrades P‐glycoprotein and EID1 by ubiquitination and activates the JNK and p38 pathways; however, its role in OA remains unknown. Here, the main objective of this study was to evaluate the potential effects and mechanism of FBXO21 in OA degeneration, we revealed that FBXO21 is upregulated in the cartilage of patients with OA, aging, and monosodium iodoacetate‐induced OA rats, and chondrocytes treated with interleukin‐1β, tumor necrosis factor‐α, and lipopolysaccharide. Moreover, the in vivo and in vitro knockdown of FBXO21 suppressed OA‐related cartilage degeneration, as evidenced by activated autophagy, upregulated anabolism, alleviated apoptosis, and downregulated catabolism. In contrast, its overexpression promoted OA‐related cartilage degeneration. In addition, using mass spectrometry and co‐immunoprecipitation assay, we demonstrated that the downstream mechanism of FBXO21 inhibits autophagy by interacting with and phosphorylating ERK. Furthermore, FBXO21 alleviated anabolism and enhanced apoptosis and catabolism by inhibiting autophagy in rat chondrocytes. Interestingly, for its upstream mechanism, JUNB promoted FBXO21 expression by directly targeting the FBXO21 promoter, thus further accelerating cartilage degeneration in SW1353 cells and rat chondrocytes. Overall, our findings reveal that the JUNB‐FBXO21‐ERK axis regulates OA apoptosis and cartilage matrix metabolism by inhibiting autophagy. Therefore, FBXO21 is an attractive target for regulating OA pathogenesis, and its knockdown may provide a novel targeted therapy for OA.

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“…One hour treadmill activity showed an increase in Maresin-1 content, a strong anti-inflammatory molecule, in intra-articular lavage fluid of MIA-induced rat OA. Maresin-1 was able to decrease MMP13, activate the PI3k/Akt pathway, and suppress the NF-κB p65 pathway in IL-1β-induced rat fibroblast-like synoviocytes in vitro, suggesting a pivotal role of Maresin-1 in exerting the anti-inflammatory activity of exercise [ 74 ].…”

Section: Physical Exercise As a Modulator Of Osteoarthritis Molecular Pathwaysmentioning

confidence: 99%

“…However, they also exert their action in a high number of intracellular signaling and metabolic pathways [ 26 ]. PUFAs and their metabolites act as second messengers when intercalated in the cell membrane, inhibiting the expression of MMP-13 through the inactivation of the p38MAPK and NF-κB p65 pathway, and promoting the activation of the PI3k/Akt signaling [ 58 , 74 ].…”

Section: Nutrigenomic: Role Of Nutraceuticals On Osteoarthritismentioning

confidence: 99%

Role of Physical Exercise and Nutraceuticals in Modulating Molecular Pathways of Osteoarthritis

Sire

Marotta

Marinaro

et al. 2021

IJMS

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Osteoarthritis (OA) is a painful and disabling disease that affects millions of patients. Its etiology is largely unknown, but it is most likely multifactorial. OA pathogenesis involves the catabolism of the cartilage extracellular matrix and is supported by inflammatory and oxidative signaling pathways and marked epigenetic changes. To delay OA progression, a wide range of exercise programs and naturally derived compounds have been suggested. This literature review aims to analyze the main signaling pathways and the evidence about the synergistic effects of these two interventions to counter OA. The converging nutrigenomic and physiogenomic intervention could slow down and reduce the complex pathological features of OA. This review provides a comprehensive picture of a possible signaling approach for targeting OA molecular pathways, initiation, and progression.

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Maresin-1 suppresses IL-1β-induced MMP-13 secretion by activating the PI3K/AKT pathway and inhibiting the NF-κB pathway in synovioblasts of an osteoarthritis rat model with treadmill exercise

Cited by 39 publications

References 38 publications

Role of PI3K/AKT Signaling Pathway in Nucleus Pulposus Cells

Role of PI3K/AKT Signaling Pathway in Nucleus Pulposus Cells

JUNB‐FBXO21‐ERK axis promotes cartilage degeneration in osteoarthritis by inhibiting autophagy

Role of Physical Exercise and Nutraceuticals in Modulating Molecular Pathways of Osteoarthritis

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