Sam68 Promotes NF-κB Activation and Apoptosis Signaling in Articular Chondrocytes during Osteoarthritis

Xu, Le; Sun, Chi; Zhang, Sihui; Xu, Xiangdong; Zhai, Leilei; Wang, Youhua; Wang, Shitao; Liu, Zhongbing; Cheng, Hongbing; Xiao, Min; Tao, Ran; Zhang, Dongmei

doi:10.1007/s00011-015-0872-3

Cited by 32 publications

(32 citation statements)

References 24 publications

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“…Many studies provide evidence for the role of NF-κB in mediating enhancement of apoptosis [14,15]. Apoptosis, or programmed cell death, has been suggested to have a close relationship with OA progression [29,30]. In the adult of TMJ dysfunction, apoptosis has been found in the course of joint remodeling [31].…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Genistein on Condylar Cartilage through Downregulating NF-κB Expression in Experimentally Created Osteoarthritis Rats

Jian

Ding

et al. 2019

BioMed Research International

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Temporomandibular joint osteoarthrosis (TMJOA) is characterised by chronic inflammatory changes, with subsequent gradual loss of joint cartilage. NF-κB is a crucial transcription factor in the course of inflammatory and immune responses, which are involved in OA pathology activated by proinflammatory cytokines. Genistein is known to have anti-inflammation and modulation of metabolic pathways through repression of the NF-κB signaling pathway in inflammatory disease. But so far, studies on the effects of genistein on TMJOA are very limited. So, the purpose of this study is to investigate the protective effect of genistein against experimentally induced condylar cartilage degradation through downregulating NF-κB expression in created osteoarthritis rats in vivo. Male SD rats were created as temporomandibular joint osteoarthritis models and administered through oral gavage with low and high dosage genistein (30 mg/kg and 180 mg/kg, respectively) daily for 4 weeks. The morphological changes of the condylar cartilage were studied with HE and Masson staining. The expressions of p65 and inflammatory cytokines (IL-1β and TNFα) were detected using immunohistochemistry and real-time PCR. The results showed that experimentally created osteoarthritis reduced the condylar cartilage thickness of rats and increased the gene expression of cytokines (IL-1β and TNFα) and positive cells of p65. Genistein treatment had positive effects on the condylar cartilage renovation, while high dose genistein treatment had more significant effects on the reversing of OA changes and reduction of the expression of p65 and inflammatory cytokines (IL-1β and TNFα). The results indicated that high dose genistein treatment had obvious therapeutic effects on condyle cartilage damages of OA rats. The mechanism may be that genistein suppresses the NF-κB expression activated by inflammatory cytokines.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Genistein on Condylar Cartilage through Downregulating NF-κB Expression in Experimentally Created Osteoarthritis Rats

Jian

Ding

et al. 2019

BioMed Research International

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“…MMP-3, MMP-9, and MMP-13 levels increased in animals induced with osteoarthritis [18,30,33,34,63], but the TIMP-2 level was shown to decline [72]. Similarly, MMP-13, MMP-3, MMP-2, and MMP-9 increased in the cell line model of osteoarthritis [26,28]. Furthermore, several studies have investigated the MMP-13 level in osteoarthritis patients, and consistent observation is obtained, whereby the MMP-13 level increased significantly in patients with osteoarthritis [30,48,59,[73][74][75][76][77][78].…”

Section: The Role Of Matrix Metalloproteinases (Mmps) In Osteoarthritismentioning

confidence: 95%

“…TNF-α and IL-1β have been used to trigger inflammation in chondrocyte and synoviocyte culture. Upon stimulation, the cells release IL-6 [26], IL-8 [27], IL-10 [28], IL-1β [29], and TNF-α [28]. Similar cytokine profile was increased in animal models of osteoarthritis [18,[30][31][32][33][34].…”

Section: The Role Of Cytokines In Osteoarthritismentioning

confidence: 99%

“…It is triggered by proinflammatory cytokines and ECM degradation products [89]. The activated NF-κB will 11 Mediators of Inflammation modulate the expression of several cytokines, chemokines, and matrix-degrading enzymes, which explains its role in regulating catabolic events in osteoarthritis [26]. The NF-κB signaling pathway begins with the activation of IκB kinase (IKK), resulting in phosphorylation and degradation of IκBα by the proteasome.…”

Section: The Role Of Signaling Pathways and Other Inflammatory Componmentioning

confidence: 99%

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The Role of Inflammation in the Pathogenesis of Osteoarthritis

Chow

Chin

2020

Mediators of Inflammation

363

221

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A joint is the point of connection between two bones in our body. Inflammation of the joint leads to several diseases, including osteoarthritis, which is the concern of this review. Osteoarthritis is a common chronic debilitating joint disease mainly affecting the elderly. Several studies showed that inflammation triggered by factors like biomechanical stress is involved in the development of osteoarthritis. This stimulates the release of early-stage inflammatory cytokines like interleukin-1 beta (IL-1β), which in turn induces the activation of signaling pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), and mitogen-activated protein kinase (MAPK). These events, in turn, generate more inflammatory molecules. Subsequently, collagenase like matrix metalloproteinases-13 (MMP-13) will degrade the extracellular matrix. As a result, anatomical and physiological functions of the joint are altered. This review is aimed at summarizing the previous studies highlighting the involvement of inflammation in the pathogenesis of osteoarthritis.

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“…The activated NF-κB was detected in OA synovial tissue, which contributed to the initiation and maintenance of chronic inflammation [31]. In addition, it has been proved that NF-κB activation promoted synovial hyperplasia via promoting cell proliferation and inhibiting c-myc–induced apoptosis [32]. The c-Jun NH2-terminal Kinase (JNK) pathway represents one sub-group of the mitogen-activated protein (MAP) kinases.…”

Section: Discussionmentioning

confidence: 99%

MiR-125b Inhibits LPS-Induced Inflammatory Injury via Targeting MIP-1α in Chondrogenic Cell ATDC5

Jia

Wang

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Chondrocyte apoptosis is largely responsible for cartilage degeneration in osteoarthritis (OA). MicroRNAs (miRNAs) play an important role in chondrogenesis and cartilage remodeling. This study explored the effect of miR-125b on inflammatory injury in chondrogenic cells. Methods: LPS was used to simulate inflammatory injury in murine chondrogenic ATDC5 cell lines. Targeting effect of miR-125b on MIP-1α 3’UTR was assessed by dual luciferase activity assay. Regulatory effect of miR-125b on MIP-1α expression and the potential regulatory mechanism on inflammatory injury were assessed by Western blot. Results: miR-125b expression was decreased in LPS-induced ATDC5 cells and overexpression of miR-125b inhibited LPS-induced cell viability decline, the rise of apoptosis and inflammatory factors’ productions. MIP-1α expression was negatively related to miR-125b, and miR-125b directly targeted with 3’UTR of MIP-1α. Knockdown of miR-125b promoted LPS-induced inflammatory response via upregulation of MIP-1α. miR-125b expression in LPS-induced ATDC5 cells was negatively related with activations of NF-κB and JNK signaling pathways. Overexpression of miR-125b inhibited LPS-induced inflammation injury via suppressing MIP-1α expression and inhibiting activations of NF-κB and JNK signaling pathways. Conclusion: miR-125b could play an important role in inflammatory injury of chondrogenic cells and miR-125b affected inflammatory injury of ATDC5 cells via regulating expression of MIP-1α and regulating NF-κB and JNK signaling pathways.

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Sam68 Promotes NF-κB Activation and Apoptosis Signaling in Articular Chondrocytes during Osteoarthritis

Abstract: The highly expressed Sam68 promotes NF-κB signaling activation, catabolic gene expression and cellular apoptosis in TNF-α-treated chondrocytes, which may provide better insights into the pathophysiology of OA and a potential target for its treatment.

Cited by 32 publications

References 24 publications

Protective Effect of Genistein on Condylar Cartilage through Downregulating NF-κB Expression in Experimentally Created Osteoarthritis Rats

Protective Effect of Genistein on Condylar Cartilage through Downregulating NF-κB Expression in Experimentally Created Osteoarthritis Rats

The Role of Inflammation in the Pathogenesis of Osteoarthritis

MiR-125b Inhibits LPS-Induced Inflammatory Injury via Targeting MIP-1α in Chondrogenic Cell ATDC5

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