Serine protease inhibitor E2 protects against cartilage tissue destruction and inflammation in osteoarthritis by

Linzhu Wang1, Shuangshuang Chen1, Huizhen Zhang1

  • 1Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), College of Pharmacy, Harbin Medical University, Harbin, PR China.

PubMed
Abstract

Insights

Serine peptidase inhibitor clade E member 2 (serpinE2) shows protective effects in osteoarthritis (OA) by reducing cartilage degeneration and inflammation. Upregulating serpinE2 may offer new therapeutic strategies for OA treatment.

Area of Science:

  • Molecular Biology
  • Genetics
  • Immunology

Background:

  • Osteoarthritis (OA) is a degenerative joint disease with no current disease-modifying treatments.
  • Cartilage degeneration and inflammation are key pathological features of OA.

Purpose of the Study:

  • To identify pathogenic genes involved in OA.
  • To elucidate the underlying molecular mechanisms of these genes in OA pathogenesis.

Main Methods:

  • Combined single-cell and bulk transcriptome analysis of OA cartilage.
  • In vivo studies using a rat model of OA (monosodium iodoacetate-induced).
  • In vitro experiments on chondrocytes involving gene silencing and exogenous protein administration.

Main Results:

  • Serine peptidase inhibitor clade E member 2 (serpinE2) expression is elevated and hypomethylated in OA, correlating with collagen pathway activity.
  • Silencing serpinE2 worsened OA in rats, while exogenous serpinE2 ameliorated cartilage degeneration, pain, and synovitis.
  • Exogenous serpinE2 inhibited NLRP3 inflammasome activation, reduced reactive oxygen species (ROS), and suppressed NF-κB signaling in chondrocytes.

Conclusions:

  • SerpinE2 demonstrates a protective role in both cartilage and synovium in OA.
  • SerpinE2 gene therapy or agents that boost serpinE2 levels are potential therapeutic avenues for OA.

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
963
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.7K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.4K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
120
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.3K