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A Non-Invasive Method for Generating the Cyclic Loading-Induced Intra-Articular Cartilage Lesion Model of the Rat Knee
Published on: July 5, 2021
Intra-articular delivery of Si-Vangl2 limits cartilage degeneration in an osteoarthritis rat model
Peiru Li1, Ke Zhang1,2, Zhuoying Li1
1Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Abstract:
Osteoarthritis (OA) is driven by progressive cartilage degeneration associated with dysregulated chondrocyte metabolism and inflammatory signaling, for which effective disease-modifying treatments remain limited. In this study, we observed that Van Gogh-like 2 (Vangl2), a core component of the non-canonical Wnt/planar cell polarity (PCP) pathway, is upregulated in chondrocytes under inflammatory conditions. In a collagenase-induced OA rat model, intra-articular delivery of small interfering RNA targeting Vangl2 (Si-Vangl2) attenuated cartilage degeneration and partially preserved cartilage structure and matrix. Immunohistochemical (IHC) analysis showed that Vangl2 silencing increased the expression of anabolic and proliferative markers including Sox9, type II collagen (Col2), aggrecan, and PCNA, while reducing the levels of catabolic enzymes including matrix metalloproteinase 3 (MMP3), MMP13, as well as the hypertrophic marker type X collagen (Col10a1). Wnt5a-associated inflammatory signaling through JNK and NF-κB pathways, was also diminished following Si-Vangl2 treatment. In vitro findings suggest that Vangl2 act as a pro-chondrogenic factor, examined by real-time quantitative polymerase chain reaction (RT-qPCR), Western blot and cell counting kit-8 (CCK-8) assays. These results indicate that Si-Vangl2 limits cartilage degeneration by enhancing anabolic activity, suppressing matrix degradation and chondrocyte hypertrophy, and restoring chondrocyte homeostasis in OA.
Insights
Targeting Van Gogh-like 2 (Vangl2) with small interfering RNA (Si-Vangl2) in osteoarthritis (OA) reduces cartilage degeneration. This approach enhances anabolic activity and restores chondrocyte homeostasis, offering a potential disease-modifying treatment for OA.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Osteoarthritis (OA) involves progressive cartilage degeneration and dysregulated chondrocyte metabolism.
- Current disease-modifying treatments for OA are limited.
- The non-canonical Wnt/planar cell polarity (PCP) pathway component, Van Gogh-like 2 (Vangl2), is upregulated in chondrocytes during inflammation.
Purpose of the Study:
- To investigate the role of Vangl2 in OA pathogenesis.
- To evaluate the therapeutic potential of Vangl2 inhibition using small interfering RNA (Si-Vangl2) in an OA rat model.
Main Methods:
- A collagenase-induced OA rat model was used.
- Intra-articular delivery of Si-Vangl2 was administered.
- Immunohistochemistry (IHC), real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, and cell counting kit-8 (CCK-8) assays were performed.
Main Results:
- Si-Vangl2 treatment attenuated cartilage degeneration and preserved cartilage structure.
- Vangl2 silencing increased anabolic markers (Sox9, Col2, aggrecan, PCNA) and decreased catabolic markers (MMP3, MMP13, Col10a1).
- Inflammatory signaling pathways (JNK, NF-κB) were diminished, and Vangl2 was identified as a pro-chondrogenic factor in vitro.
Conclusions:
- Si-Vangl2 limits OA cartilage degeneration by enhancing anabolic activity and suppressing matrix degradation.
- Vangl2 inhibition restores chondrocyte homeostasis and reduces chondrocyte hypertrophy.
- Targeting Vangl2 represents a promising therapeutic strategy for osteoarthritis.
