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Updated: Jun 15, 2025

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
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.
Objective:
OA is a chronic disease characterized by cartilage degeneration and inflammation, with no approved disease-modifying drugs. This study aimed to identify pathogenic genes and elucidate their mechanism in OA.
Methods:
We systematically identified pathogenic genes combined sing-cell and bulk transcriptome profiles of cartilage tissues in OA. Adenovirus carrying the serpin peptidase inhibitor clade E member 2 (serpinE2) or exogenous serpinE2 was injected into monosodium iodoacetate (MIA)-induced OA-model rats. Histological analysis, immunohistochemistry and Alcian blue staining were performed. In vitro, immunofluorescence, quantitative real-time PCR (RT-qPCR), ELISA and western blot assays were performed.
Results:
serpinE2 exhibited elevated expression and hypomethylation, showing a positive association with collagen pathway activities in patients with OA. Silencing serpinE2 aggravated MIA-induced knee cartilage degeneration in OA-model rats. Conversely, the intra-articular injection of exogenous serpinE2 ameliorated articular cartilage degeneration, reduced pain-related behavioural responses and relieve synovitis in MIA-induced OA-model rats. Exogenous serpinE2 not only attenuated the elevation of NLRP3, IL-1β and caspase1 expression levels but also restored the reduction in cell viability induced by lipopolysaccharide (LPS) in chondrocytes. Mechanistically, we found that exogenous serpinE2 inhibited LPS-induced reactive oxygen species (ROS) release and NF-κB signalling activation.
Conclusions:
serpinE2 plays a protective role in cartilage and synovium tissues, suggesting that serpinE2 gene transfer or molecules that upregulate serpinE2 expression could be therapeutic candidates for OA.
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.
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