Roles of Hippo–YAP/TAZ signalling in intervertebral disc degeneration

Zheng-Wei, Shi; Yuan, Tuo; Chao-Shuai, Feng; Li, Zhu; Song, Zongrang; Liu, Tuan-Jiang; Hao, Ding-Jun

doi:10.1016/j.biopha.2022.114099

Cited by 8 publications

(2 citation statements)

References 72 publications

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“…Additionally, it disrupted H 2 O 2 -induced phosphorylation of mammalian STE20-like protein kinase 1/2 (Mst1/2) and large tumor suppressor 1/2 (Lats1/2), reversed H 2 O 2 -induced reduction of Yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz) and diminished H 2 O 2 -induced ROS increase [ 60 ]. The anti-senescence effect was abolished after the blockade of Hippo signaling by Yap/Taz inhibition, consistent with the established close association of Hippo signaling activity with NP cell senescence [ 192 , 193 ]. In vivo, morroniside has been shown to decrease to a great extent the elevated expression of p53 and p21 WAF1 and positive SA-β-Gal staining, while it significantly alleviated the decrease in aggrecan and increase in ADAMTS-5 in the NP tissues of a lumbar spine instability surgery-induced mouse IDD model.…”

Section: Plant-derived Compounds With a Reported Senotherapeutic Acti...supporting

confidence: 83%

Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

Mavrogonatou,

Kletsas

2024

Metabolites

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Chronic low back pain, a major cause of disability with a great global socioeconomic impact, has been inextricably associated with intervertebral disc degeneration. On the other hand, an enhanced number of senescent cells has been identified in aged and degenerated intervertebral discs and their senescence-associated secretory phenotype (SASP) has been connected with qualitative/quantitative alterations in the extracellular matrix and ultimately with the disturbance of tissue homeostasis. Given that selective elimination of senescent cells (by the so-called senolytics) or amendment of their secretome towards a less catabolic/inflammatory phenotype (by molecules known as senomorphics) has been reported to alleviate symptoms of several age-associated diseases and to improve tissue quality during aging, here we will review the emerging role of senolytic and senomorphic agents derived from plants and natural products against intervertebral disc degeneration. The mode of action of these senotherapeutics, as well as the challenges in their practical application, will also be explicitly discussed in an attempt to direct their more targeted and effective use in exclusive or combinatorial therapeutic schemes for the prevention and/or treatment of disc degenerative disorders.

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Section: Plant-derived Compounds With a Reported Senotherapeutic Acti...supporting

confidence: 83%

Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

Mavrogonatou,

Kletsas

2024

Metabolites

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“…Furthermore, we delved into additional mechanisms through which HNK inhibited malignant behavior of OVCA cells. Prior investigations have elucidated the engagement of the Hippo‐YAP/TAZ pathway in various human diseases, encompassing cancers and proliferative disorders 25,26 . Importantly, the signaling pathway has the capacity to regulate cancer cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Honokiol regulates ovarian cancer cell malignant behavior through YAP/TAZ pathway modulation

Liu,

Zhang,

Xia

et al. 2024

J of Obstet and Gynaecol

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BackgroundOvarian cancer (OVCA) stands as one of the most fatal gynecological malignancies. Honokiol (HNK) has been substantiated by numerous studies for its anti‐tumor activity against malignancies including OVCA. Consequently, this work was designed to elucidate the impact of HNK‐mediated modulation of the YAP/TAZ pathway on the biological functions of OVCA cells.MethodsOVCA cells were subjected to treatment with varying concentrations (0, 25, 50, 75, and 100 μM) of HNK, concomitant with the administration of YAP agonist (XMU). Assessment of cellular viability was executed employing the CCK‐8 assay, while quantification of cellular proliferation transpired via colony formation assays. Apoptosis was ascertained using flow cytometry, and expression of apoptosis‐related proteins (caspase‐3, Bcl‐2, Bax), EMT‐related proteins (E‐cadherin, N‐cadherin), migration‐associated proteins (MMP‐2, MMP‐9), and YAP/TAZ pathway‐related proteins was evaluated by western blot. Transwell experiments were conducted to assess cellular migratory and invasive propensities. Xenograft tumor models were built to observe tumor growth (volume and weight), apoptosis was assessed by TUNEL staining, and Ki67 expression was evaluated through IHC.ResultsHNK exerted inhibitory effects on the viability and proliferative capacity of OVCA cells, elicited apoptotic responses, curtailed the migratory and invasive tendencies of cells, and downregulated the YAP/TAZ pathway. Stimulation with YAP agonist (XMU‐MP‐1) partially attenuated the impacts of HNK on OVCA cell biology. Experiments in vivo confirmed that HNK inhibited OVCA tumor growth.ConclusionThe outcomes of this investigation conclusively established that HNK orchestrated the modulation of the YAP/TAZ pathway, thereby exerting control over the malignant phenotypic manifestations of OVCA cells. The ascertained function of HNK in restraining cellular proliferation and tumor progression provided novel evidence of its anti‐proliferative activity within OVCA cells.

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Biological effects of material mechanics and its application in soft tissue regeneration

2024

Bioactive Materials for Soft Tissue Regeneration

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Roles of Hippo–YAP/TAZ signalling in intervertebral disc degeneration

Cited by 8 publications

References 72 publications

Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

Plant-Derived Senotherapeutics for the Prevention and Treatment of Intervertebral Disc Degeneration and Aging

Honokiol regulates ovarian cancer cell malignant behavior through YAP/TAZ pathway modulation

Biological effects of material mechanics and its application in soft tissue regeneration

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