This study aims to investigate the function and related mechanism of gene in intervertebral disc (IVD) degeneration of mice. X-ray, immunohistochemical staining, and alkaline phosphatase (ALP) histochemical staining were used to analyze the phenotypic difference of the intervertebral discs of 4-week-old mice with P27 gene knockout (P27) and wild-type (WT) mice in the same brood. Protein in the intervertebral disc was extracted and western blot analysis was employed to detect the changes in the expression of related molecules in the Shh-signal pathways, including Shh, Patched, Smoothened and Gli2. As a result, the ALP histochemical staining revealed that the ALP-positive area of mice in the P27 group was obviously increased compared to the 4-week-old mice of the same brood in the WT group. In addition, the Col-I immunohistochemical staining showed that the Col-I-positive area of mice in the P27 group was significantly increased compared to mice in the WT group. Furthermore, Smo-positive cell rate of mice in the P27 group was apparently increased compared to mice in the WT group. Western blot analysis revealed that in terms of changes of protein expression levels of Shh, Patched, Smoothened and Gli2 in the intervertebral disc, protein expression levels of Shh, Patched, Smoothened and Gli2 of mice in the P27 group were significantly increased compared to those of mice in the WT group. The results show that P27 deficiency activates the expression of Shh-signal pathway and promotes the proliferation of osteoblast, thus, playing a role in promoting IVD degeneration, which provides a scientific and reliable experimental basis for the treatment of the IVD degeneration-related diseases in clinical practice.
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http://dx.doi.org/10.3892/etm.2017.4584 | DOI Listing |
Int J Mol Sci
January 2025
MRL, Merck & Co., Inc., Rahway, NJ 07065, USA.
Despite the success of combination antiretroviral therapy (cART) to suppress HIV replication, HIV persists in a long-lived reservoir that can give rise to rebounding viremia upon cART cessation. The translationally active reservoir consists of HIV-infected cells that continue to produce viral proteins even in the presence of cART. These active reservoir cells are implicated in the resultant viremia upon cART cessation and likely contribute to chronic immune activation in people living with HIV (PLWH) on cART.
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January 2025
Department of Oral Pathology, Howard University, 600 W Street NW, Washington, DC 20059, USA.
MEK inhibitors, such as trametinib, have shown therapeutic potential in head and neck squamous cell carcinoma (HNSCC). However, the factors influencing cancer cell sensitivity and resistance to MEK inhibition remain poorly understood. In our study, we observed that MEK inhibition significantly reduced the expression of MYC, a transcription factor critical for the therapeutic response.
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January 2025
Allergen-reactive T helper (Th) 2 cells play a pivotal role in initiating asthma pathogenesis. The absence or interruption of CD28 signaling causes significant consequences for T-cell activation, leading to reduced cell proliferation and interleukin (IL)-2 production. A novel compound, Cyn-1324, exhibits a higher binding affinity to CD28 than CD80.
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February 2025
Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University, Sector-125, Noida 201313, Uttar Pradesh, India. Electronic address:
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and grave malignancies with confined and ineffective therapeutic options. XPO1 is a critical regulator of nuclear export and activation of tumor suppressor proteins. The present study evaluated the therapeutic potential and molecular mechanisms of XPO1 inhibition against PDAC.
View Article and Find Full Text PDFViruses
November 2024
Laboratory for Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp (UA), Universiteitsplein 1 S.7, 2610 Antwerp, Belgium.
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children, elderly and immunocompromised patients worldwide. The RSV fusion (F) protein, which has 5-6 N-glycosylation sites depending on the strain, is a major target for vaccine development. Two to three of these sites are located in the p27 peptide, which is considered absent in virions.
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