Expression of VEGF-A Signaling Pathway in Cartilage of ACLT-induced Osteoarthritis Mouse Model

Abstract

Background Anterior cruciate ligament transection surgery (ACLT)-induced OA model was often used to investigate the molecular mechanism of knee osteoarthritis (KOA). Researches have shown that vascular endothelial growth factor (VEGF) played an important role in OA. The present study aimed to investigate the pathological changes after ACLT surgery and reveal the expression characteristics of the VEGF-A/VEGFR2 signaling pathway in this model. Methods Moderate KOA model was established by ACLT, and 1, 2, 4, 8, and 12 weeks after surgery, hematoxylin-eosin (HE) and Safranin-O(S-O) staining were used to detect the pathological changes in mouse knee cartilage, and the matrix biomarkers A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5(ADAMTS5), Collagen II (COL-II) were detected using immunohistochemistry (IHC), CD31 was detected by immunofluorescence (IF) to show the vascular invasion in cartilage, and proteins expression of VEGF-A pathway were detected by Western blot (WB). Meanwhile, the inflammatory biomarkers cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in cartilage were detected by WB. Results ACLT surgery can lead to degeneration of cartilage in mice, and the characteristics of the lesion were time-dependent. The ADAMTS5-positive cells increased while COL-II decreased in OA cartilage with time, and new blood vessels labeled by CD31 can be seen from 1 week in OA cartilage, and increased in 8 and 12 weeks. The expression of VEGF-A, VEGFR2, COX-2, and iNOS were higher than control groups, which were basically consistent with the degree of osteoarthritis. Conclusions The degenerative degree of articular cartilage was time-dependent; angiogenesis and inflammation were important pathological changes of cartilage in KOA. The expression of the VEGF-A/VEGFR2 signaling pathway was basically correlated with the degree of KOA.

A nitric oxide responsive AIE probe for detecting the progression of osteoarthritis

“…32 ACLT induced degradation of articular cartilage was time-dependent, and many inflammation factors including nitric oxide (NO) and vascular endothelial growth factor (VEGF) were positively correlated with the degree of KOA. 33 Time points for in vivo OA monitoring were conducted in accordance with the timeline in Fig. 4(A).…”

Treatment outcomes of injectable thermosensitive hydrogel containing bevacizumab in intervertebral disc degeneration

“…These findings suggest the local administration of bevacizumab for the treatment of disc degeneration has potential clinical application. Some studies have observed a relationship between VEGF and chondrocytes in terms of physiology and pathology (Chen et al, 2019;Qian et al, 2021;Xiao et al, 2021;Xiaoshi et al, 2021), but there was a lack of relevant studies in IVD. We found that VEGF is highly expressed in IDD of humans and rats.…”

“…Some studies have observed a relationship between VEGF and chondrocytes in terms of physiology and pathology ( Chen et al, 2019 ; Qian et al, 2021 ; Xiao et al, 2021 ; Xiaoshi et al, 2021 ), but there was a lack of relevant studies in IVD. We found that VEGF is highly expressed in IDD of humans and rats.…”

Knee osteoarthritis: A review of animal models and intervention of traditional Chinese medicine

“… 62 Qian et al. 63 established a moderate mouse KOA model using ACLT, and hematoxylin–eosin (HE) and safranin‐O (S‐O) staining were used to detect pathological changes in knee cartilage at 1, 2, 4, 8, and 12 weeks after surgery. It was found that the characteristics of cartilage degeneration in mice were time dependent and the expression of inflammatory factors was high, which were basically consistent with the degree of KOA, ensuring the success of the model.…”