Periodic Mechanical Stress Stimulates GIT1-Dependent Mitogenic Signals in Rat Chondrocytes Through ERK1/2 Activity

Tang, Jilei; Jiang, Xuefeng; Sun, Huiqing; Nong, Luming; Shen, Nan; Gu, Yanqing

doi:10.1159/000494513

Cited by 4 publications

(3 citation statements)

References 38 publications

(46 reference statements)

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“…Periodic mechanical load activates downstream protein kinase C (PKC) signals by stimulating chondrocytes α5β1 integrin, which can cause hyperpolarization of chondrocyte membrane (Wright et al, 1997). Mechanical signal pathways mediated by integrins are involved in the proliferation and matrix synthesis of chondrocytes, such as integrin β1-Src-GIT ArfGAP 1 (GIT1)-focal adhesion kinase (FAK) (Tyr576/577)extracellular regulated protein kinase 1/2 (ERK1/2), integrin β1-FAK(Tyr397)-ERK1/2, and integrin β1-Ca2+/calmodulin dependent protein kinase II (CaMKII)-Proline-rich tyrosine kinase 2 (Pyk2)-ERK1/2 signal pathway (Liang et al, 2017;Ren et al, 2018). Studies suggested that the death signaling pathway mediated by integrins also participated in the process that excessive mechanical load acting on cartilage explants (Jang et al, 2014).…”

Section: Integrins In Chondrocyte Mechanotransductionmentioning

confidence: 99%

Mechanistic Insight Into the Roles of Integrins in Osteoarthritis

Jin

Jiang²,

Wang³

et al. 2021

Front. Cell Dev. Biol.

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Osteoarthritis (OA), one of the most common degenerative diseases, is characterized by progressive degeneration of the articular cartilage and subchondral bone, as well as the synovium. Integrins, comprising a family of heterodimeric transmembrane proteins containing α subunit and β subunit, play essential roles in various physiological functions of cells, such as cell attachment, movement, growth, differentiation, and mechanical signal conduction. Previous studies have shown that integrin dysfunction is involved in OA pathogenesis. This review article focuses on the roles of integrins in OA, especially in OA cartilage, subchondral bone and the synovium. A clear understanding of these roles may influence the future development of treatments for OA.

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Section: Integrins In Chondrocyte Mechanotransductionmentioning

confidence: 99%

Mechanistic Insight Into the Roles of Integrins in Osteoarthritis

Jin

Jiang²,

Wang³

et al. 2021

Front. Cell Dev. Biol.

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“…The GIT1 protein is one of the key regulators of FA formation and cell migration (107,108). This protein has a complex structure, containing various domains and effector sites (109).…”

Section: Mirnas and Mechanotransduction Pathwaysmentioning

confidence: 99%

Key Regulatory miRNAs and their Interplay with Mechanosensing and Mechanotransduction Signaling Pathways in Breast Cancer Progression

Najminejad

Farhadihosseinabadi

Dabaghian

et al. 2020

Molecular Cancer Research

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According to the WHO, breast cancer is the most common cancer in women worldwide. Identification of underlying mechanisms in breast cancer progression is the main concerns of researches. The mechanical forces within the tumor microenvironment, in addition to biochemical stimuli such as different growth factors and cytokines, activate signaling cascades, resulting in various changes in cancer cell physiology. Cancer cell proliferation, invasiveness, migration, and, even, resistance to cancer therapeutic agents are changed due to activation of mechanotransduction signaling. The mechanotransduction signaling is frequently dysregulated in breast cancer, indicating its important role in cancer cell features. So far, a variety of experimental investigations have been conducted to determine the main regulators of the mechanotransduction signaling. Currently, the role of miRNAs has been well-defined in the cancer process through advances in molecular-based approaches. miRNAs are small groups of RNAs (22 nucleotides) that contribute to various biological events in cells. The central role of miRNAs in the regulation of various mediators involved in the mechanotransduction signaling has been well clarified over the last decade. Unbalanced expression of miRNAs is associated with different pathologic conditions. Overexpression and downregulation of certain miRNAs were found to be along with dysregulation of mechanotransduction signaling effectors. This study aimed to critically review the role of miRNAs in the regulation of mediators involved in the mechanosensing pathways and clarify how the cross-talk between miRNAs and their targets affect the cell behavior and physiology of breast cancer cells.

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“…Several studies have reported the promoting effect of PMS on the proliferation of chondrocytes and matrix synthesis. [21][22][23][24] For example, van Valburg et al reported that joint traction provided mechanical stress to promote the repair of cartilage. 25 Additionally, Gao et al discovered that PMS significantly induced the expression of extracellular matrix (ECM) Col-2A1 and aggrecan in nucleus pulposus (NP) cells.…”

Section: Introductionmentioning

confidence: 99%

Periodic Mechanical Stress Inhibits the Development of Osteoarthritis via Regulating ATF3-Akt Axis

Lou,

Song,

Kang

et al. 2023

JIR

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Purpose The development of osteoarthritis (OA) has been linked to mechanical factors. Studies suggest that periodic mechanical stress (PMS) may be a factor contributing to cartilage repair and the onset of OA. Therefore, this study was designed to explore the effects and underlying mechanisms of PMS on OA development. Patients and Methods Firstly, surgery and interleukin (IL)-1β were used for the establishment of rat/cell models of OA, respectively. Subsequently, activating transcription factor (ATF) 3 expression was knocked down in OA rats, and OA chondrocytes were treated with different heights (0, 1, 2, 4, 8 cm) of PMS or si-ATF. Safranin O staining was used to observe the histological changes in the rat knee joint, and enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of tumor necrosis factor (TNF)-α, IL-6, and IL-8 in vivo and in vitro. Further, the expression of extracellular matrix (ECM) proteins in the rat knee joint was assessed immunohistochemistry. Flow cytometry was used to evaluate chondrocyte apoptosis. Lastly, Western blot was performed to detect the expression of related proteins of the protein kinase B (Akt) signaling pathway and ECM. Results The OA rat model was successfully constructed. Further experiments indicated that the knockdown of ATF3 not only alleviated joint swelling, pain, inflammatory response and pathological damage, but also promoted ECM synthesis and the phosphorylation of Akt in OA rats. In vitro experiments showed that PMS (4 cm) effectively inhibited cell apoptosis, decreased the levels of TNF-α, IL-6 and IL-8, promoted ECM synthesis, and activated the Akt signaling pathway in osteoarthritic chondrocytes. However, ATF3 overexpression reversed the positive effects of PMS on osteoarthritic chondrocytes. Conclusion PMS can effectively inhibit the development of OA, and its protective effects may be attributed to the down-regulation of ATF3 expression and activation of the Akt signaling pathway.

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Periodic Mechanical Stress Stimulates GIT1-Dependent Mitogenic Signals in Rat Chondrocytes Through ERK1/2 Activity

Cited by 4 publications

References 38 publications

Mechanistic Insight Into the Roles of Integrins in Osteoarthritis

Mechanistic Insight Into the Roles of Integrins in Osteoarthritis

Key Regulatory miRNAs and their Interplay with Mechanosensing and Mechanotransduction Signaling Pathways in Breast Cancer Progression

Periodic Mechanical Stress Inhibits the Development of Osteoarthritis via Regulating ATF3-Akt Axis

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