Chondrocyte apoptosis in temporomandibular joint osteoarthritis promotes bone resorption by enhancing chemotaxis of osteoclast precursors

Guo, Yan-Ning; Cui, Shengjie; Tian, Yajing; Zhao, Ningrui; Zhang, Yidan; Gan, Ye‐Hua; Zhou, Yanheng; Zhang, Jieni

doi:10.1016/j.joca.2022.04.002

Cited by 11 publications

(6 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MAPK signaling pathways have been implicated in the progression of TMJOA and is considered a major signaling pathways that regulates the disease [45][46][47]. The P38MAPK signaling pathways, for example, can stimulate the chemokine CX3CL1, worsening the course of TMJOA [48]. PLB reduced the development of periodontitis in rats by inactivating MAPK and lowering the production of inflammatory factors [49].…”

Section: Discussionmentioning

confidence: 99%

Plumbagin alleviates temporomandibular joint osteoarthritis progression by inhibiting chondrocyte ferroptosis via the MAPK signaling pathways

Cui,

Lan,

et al. 2023

Aging

View full text Add to dashboard Cite

Aims: The acceleration of osteoarthritis (OA) development by chondrocytes undergoing ferroptosis has been observed. Plumbagin (PLB), known for its potent antioxidant and anti-inflammatory properties, has demonstrated promising potential in the treatment of OA. However, it remains unclear whether PLB can impede the progression of temporomandibular joint osteoarthritis (TMJOA) through the regulation of ferroptosis. The study aims to investigate the impact of ferroptosis on TMJOA and assess the ability of PLB to modulate the inhibitory effects of ferroptosis on TMJOA. Materials and methods: The study utilized an in vivo rat model of unilateral anterior crossbite (UAC)-induced TMJOA and an in vitro study of chondrocytes exposed to H 2 O 2 to create an OA microenvironment. Various experiments including cell viability assessment, quantitative RT-PCR, western blot analysis, histology, and immunofluorescence were conducted to examine the impact of ferroptosis on TMJOA and evaluate the potential of PLB to mitigate the inhibitory effects of ferroptosis on TMJOA. Additionally, RNA-seq and bioinformatics analysis were performed to investigate the underlying mechanism by which PLB regulates ferroptosis in TMJOA. Results: Fer-1 demonstrated its potential in mitigating the advancement of TMJOA through its inhibitory effects on ferroptosis and matrix degradation in chondrocytes, thereby substantiating the role of ferroptosis in the pathogenesis of TMJOA. Furthermore, the observed protective impact of PLB on cartilage implied that PLB can modulate the inhibition of ferroptosis in TMJOA by regulating the MAPK signaling pathways. Conclusions: PLB alleviates TMJOA progression by suppressing chondrocyte ferroptosis via MAPK pathways, indicating PLB to be a potential therapeutic strategy for TMJOA.

show abstract

Section: Discussionmentioning

confidence: 99%

Plumbagin alleviates temporomandibular joint osteoarthritis progression by inhibiting chondrocyte ferroptosis via the MAPK signaling pathways

Cui,

Lan,

et al. 2023

Aging

View full text Add to dashboard Cite

show abstract

“…In fact, neuronal p‐38 MAPK have been associated with experimental models of nerve degeneration in Alzheimer's disease and HIV‐induced neurotoxicity (Corrêa & Eales, 2012; Medders et al., 2010; Schnöder et al., 2016). Recently, it has been shown that FKN‐CX 3 CR 1 signaling in TMJ arthritis is not only involved in the pain signal, but also in bone resorption, cartilage degradation, and chondrocyte apoptosis (Guo et al., 2022).…”

Section: Discussionmentioning

confidence: 99%

Blockage of the fractalkine pathway reduces hyperalgesia and prevents morphological glial alterations—Comparison between inflammatory and neuropathic orofacial pain in male rats

Lisboa,

Pereira,

Alves

et al. 2023

J of Neuroscience Research

View full text Add to dashboard Cite

This study aimed to evaluate the effects of inhibitors of the fractalkine pathway in hyperalgesia in inflammatory and neuropathic orofacial pain in male rats and the morphological changes in microglia and satellite glial cells (SGCs). Rats were submitted to zymosan‐induced arthritis of the temporomandibular joint or infraorbital nerve constriction, and treated intrathecally with a P2X7 antagonist, a cathepsin S inhibitor or a p‐38 mitogen‐activated protein kinase (MAPK) inhibitor. Mechanical hyperalgesia was evaluated 4 and 6 h following arthritis induction or 7 and 14 days following nerve ligation. The expression of the receptor CX3CR1, phospho‐p‐38 MAPK, ionized calcium‐binding adapter molecule‐1 (Iba‐1), and glutamine synthetase and the morphological changes in microglia and SGCs were evaluated by confocal microscopy. In both inflammatory and neuropathic models, untreated animals presented a higher expression of CX3CR1 and developed hyperalgesia and up‐regulation of phospho‐p‐38 MAPK, which was prevented by all drugs (p < .05). The number of microglial processes endpoints and the total branch length were lower in the untreated animals, but the overall immunolabeling of Iba‐1 was altered only in neuropathic rats (p < .05). The mean area of SGCs per neuron was significantly altered only in the inflammatory model (p < .05). All morphological alterations were reverted by modulating the fractalkine pathway (p < .05). In conclusion, the blockage of the fractalkine pathway seemed to be a possible therapeutic strategy for inflammatory and neuropathic orofacial pain, reducing mechanical hyperalgesia by impairing the phosphorylation of p‐38 MAPK and reverting morphological alterations in microglia and SGCs.

show abstract

“…15 It is the main cause of disability in middle-aged and elderly people, with increasing incidences and lack of effective treatment. 16 The etiology of OA is still unclear. 17 In order to further improve therapeutic outcomes in patients, it is necessary to have a deeper understanding of the pathogenesis of OA and discover more key proteins.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of DAPK1 attenuates IL-1β-induced extracellular matrix degradation and inflammatory response in osteoarthritis chondrocytes via regulating the p38 MAPK-signaling pathway

Wei

Chen

et al. 2022

Allergol Immunopathol

View full text Add to dashboard Cite

Objective: To reveal the possible effects of death-associated protein kinase 1 (DAPK1) on the progression of osteoarthritis (OA) and the potential underlying mechanism. Methods: The expression of DAPK1 in OA and normal samples and interleukin (IL)-1β-stimulated chondrocytes was analyzed by quantitative real-time polymerase chain reaction and Immunoblot assay. Cell viability, proliferation, and apoptosis in DAPK1-knockdown cells stimulated with IL-1β were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution, 5-ethynyl-2′-deoxyuridine staining and flow cytometry. The chondrocyte degradation and inflammatory response in IL-1β-induced chondrocytes were investigated by Immunoblot analysis and enzyme-linked-immunosorbent serologic assay. In addition, the effect of DAPK1 on p38 mitogen-activated protein kinase (MAPK) activation was analyzed by immunoblot assay. Results: This study revealed that DAPK1 was highly expressed in OA patients and IL-1β-induced chondrocytes. Down-regulation of DAPK1 enhanced IL-1β-induced chondrocyte proliferation. DAPK1 knockdown inhibited IL-1β-induced chondrocyte degradation. In addition, DAPK1 depletion inhibited IL-1β-induced chondrocyte inflammation. Mechanically, it was revealed that down-regulation of DAPK1 could inhibit the p38 MAPK pathway, and therefore affected progression of OA. Conclusion: DAPK1 knockdown attenuates IL-1β-induced extracellular matrix degradation and inflammatory response in OA chondrocytes by regulating the p38 MAPK pathway.

show abstract

Chondrocyte apoptosis in temporomandibular joint osteoarthritis promotes bone resorption by enhancing chemotaxis of osteoclast precursors

Cited by 11 publications

References 30 publications

Plumbagin alleviates temporomandibular joint osteoarthritis progression by inhibiting chondrocyte ferroptosis via the MAPK signaling pathways

Plumbagin alleviates temporomandibular joint osteoarthritis progression by inhibiting chondrocyte ferroptosis via the MAPK signaling pathways

Blockage of the fractalkine pathway reduces hyperalgesia and prevents morphological glial alterations—Comparison between inflammatory and neuropathic orofacial pain in male rats

Knockdown of DAPK1 attenuates IL-1β-induced extracellular matrix degradation and inflammatory response in osteoarthritis chondrocytes via regulating the p38 MAPK-signaling pathway

Contact Info

Product

Resources

About