Mechanical stress protects against osteoarthritis via regulation of the AMPK/NF‐κB signaling pathway

Yang, Yue; Wang, Yan; Kong, Yawei; Zhang, Xiaoning; Zhang, He; Ye, Gang; Bai, Lan

doi:10.1002/jcp.27592

Cited by 51 publications

(57 citation statements)

References 42 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…AMPK/NF-κB pathway is a sensitive signaling mechanism involved in OA cartilage degradation and inflammatory response. Regulation of this pathway is beneficial to the prevention of OA [22].…”

Section: Introductionmentioning

confidence: 99%

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

Wang¹,

Fang²,

Ye³

et al. 2020

Bioscience Reports

View full text Add to dashboard Cite

Purpose: To explore the regulatory mechanism of miR-137 and transcription factor 4 (TCF4) in the progression of osteoarthritis (OA). Patients and Methods: The expressions of miR-137 and TCF4 were detected in OA cartilage tissue, chondrocytes and OA rat cartilage tissue. miR-137 and TCF4 were up-regulated or down-regulated and transfected into chondrocytes and OA rat cartilage tissue. The gene expression, protein level, cell proliferation, apoptosis and inflammatory factors were detected, respectively. LPS and anterior cruciate ligament transection (ACLT) on the right knee were used to induce chondrocyte inflammation and establish rat OA model, respectively. Results: miR-137 was low expressed in cartilage tissue of OA group, while TCF4 expression and protein level were significantly higher, showing significant negative correlation. In LPS group, chondrocyte activity was significantly inhibited, cell apoptosis ability was significantly enhanced, and the levels of inflammatory factors TNF-α, IL-1β, IL-6 were significantly increased. However, the above results were significantly improved after the up-regulation of miR-137 or down-regulation of TCF4. Double luciferase report revealed that miR-137 and TCF4 had targeted relationship. LPS induced activation of AMPK/NF-κB pathway and higher level of apoptosis. AMPK/NF-κB pathway inhibitor C could inhibit activation of this pathway, and up-regulation of miR-137 or down-regulation of TCF4 could significantly weaken the regulation of LPS on the pathway and apoptosis. Analysis of OA rat model showed that over-expression of miR-137 could inhibit up-regulation of inflammatory factors and activation of AMPK/NF-κB pathway. Conclusion: miR-137 targets the inhibition of TCF4 to reverse the progression of OA through the AMPK/NF-κB signaling pathway.

show abstract

Section: Introductionmentioning

confidence: 99%

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

Wang¹,

Fang²,

Ye³

et al. 2020

Bioscience Reports

View full text Add to dashboard Cite

show abstract

“…It is characterized by progressive degeneration of the cartilage and extracellular matrix (ECM) [2,3]. OA progression has been linked to obesity, inflammation, and mechanical stress [4,5]. The specific molecular mechanism of OA remains unclear, but it is clearly complex.…”

Section: Introductionmentioning

confidence: 99%

Catalpol Attenuates IL-1β Induced Matrix Catabolism, Apoptosis and Inflammation in Rat Chondrocytes and Inhibits Cartilage Degeneration

et al. 2019

View full text Add to dashboard Cite

BackgroundChondrocyte dysfunction and apoptosis are 2 major features during the progression of osteoarthritis. Catalpol, an iridoid glycoside isolated from the root of Rehmannia, is a valuable medication with anti-inflammatory, anti-oxidative, and anti-apoptotic effects in various diseases. However, whether catalpol protects against osteoarthritis has not been investigated.Material/MethodsTo assess the role of catalpol in osteoarthritis and the potential mechanism of action, chondrocytes were treated with interleukin (IL)-1β and various concentrations of catalpol. Catabolic metabolism, apoptotic level and relative signaling pathway were measured by western blot, real-time polymerase chain reaction and immunofluorescence staining. Meanwhile, we assess the cartilage degeneration in an experimental rat model using Safranin O fast green staining and cartilage was graded according to the Osteoarthritis Research Society International (OARSI) system.ResultsThe results showed that catalpol prevented chondrocyte apoptotic level triggered by IL-1β, suppressed the release of catabolic enzymes, and inhibited the degradation of extracellular matrix induced by IL-1β. Catalpol also inhibited the nuclear factor kappa B (NF-κB) pathway, reduced the production of inflammatory cytokines (IL-6, tumor necrosis factor-α) in IL-1β-treated chondrocytes, and partially reversed cartilage degeneration in the knee joint in animal model of osteoarthritis.ConclusionsOur work suggested that catalpol treatment attenuates IL-1β-induced inflammatory response and catabolism in rat chondrocytes by inhibiting the NF-κB pathway, suggesting the therapeutic potential of catalpol for the treatment of osteoarthritis.

show abstract

“…NF-kappaB is an important transcription factor that plays a crucial role in OA. More NF-kappaB in the nucleus means more activity and inflammation (Yang et al, 2018b). We investigated whether RGFP966 could reverse OA progression by regulating NF-kappaB activity.…”

Section: Resultsmentioning

confidence: 99%

The Therapeutic Effects of Treadmill Exercise on Osteoarthritis in Rats by Inhibiting the HDAC3/NF-KappaB Pathway in vivo and in vitro

Zhang

Yang

et al. 2019

Front. Physiol.

Self Cite

View full text Add to dashboard Cite

Osteoarthritis (OA) is a disease characterized by non-bacterial inflammation. Histone deacetylase 3 (HDAC3) is a crucial positive regulator in the inflammation that leads to the development of non-OA inflammatory disease. However, the precise involvement of HDAC3 in OA is still unknown, and the underlying mechanism of exercise therapy in OA requires more research. We investigated the involvement of HDAC3 in exercise therapy-treated OA. Expression levels of HDAC3, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), matrix metalloproteinase-13 (MMP-13), HDAC3 and nuclear factor-kappaB (NF-kappaB) were measured by western blotting, reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Cartilage damage and OA evaluation were measured by hematoxylin and eosin staining and Toluidine blue O staining according to the Mankin score and OARSI score, respectively. We found that moderate-intensity treadmill exercise could relieve OA. Meanwhile, the expression of HDAC3, MMP-13, ADAMTS-5 and NF-kappaB decreased, and collagen II increased in the OA + moderate-intensity treadmill exercise group (OAM) compared with the OA group (OAG) or OA + high- or low-intensity treadmill exercise groups (OAH or OAL). Furthermore, we found the selective HDAC3 inhibitor RGFP966 could also alleviate inflammation in OA rat model through inhibition of nuclear translocation of NF-kappaB. To further explore the relationship between HDAC3 and NF-kappaB, we investigated the change of NF-kappaB relocation in IL-1β-treated chondrocytes under the stimulation of RGFP966. We found that RGFP966 could inhibit the expression of inflammatory markers of OA via regulation of HDAC3/NF-kappaB pathway. These investigations revealed that RGFP966 is therefore a promising new drug for treating OA.

show abstract

Mechanical stress protects against osteoarthritis via regulation of the AMPK/NF‐κB signaling pathway

Cited by 51 publications

References 42 publications

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

Catalpol Attenuates IL-1β Induced Matrix Catabolism, Apoptosis and Inflammation in Rat Chondrocytes and Inhibits Cartilage Degeneration

The Therapeutic Effects of Treadmill Exercise on Osteoarthritis in Rats by Inhibiting the HDAC3/NF-KappaB Pathway in vivo and in vitro

Contact Info

Product

Resources

About