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.

Background. Cancer-induced bone pain (CIBP) is a highly prevalent symptom, which afflicts vast majority of patients who suffer from cancer. The current treatment options failed to achieve satisfactory effect and the side effects were prominent. Recent randomized controlled trials (RCTs) of animal demonstrate the benefit of acupuncture for CIBP. We sought to determine if the pooled data from available RCTs supports the use of acupuncture for CIBP. Methods. A literature search for randomized controlled trials was conducted in six electronic databases from inception to May 31, 2019. Meta-analysis was performed with Review Manager 5.3 software; the publication bias was assessed by Stata 12.0 software. We used random effects model for pooling data because heterogeneity is absolute among studies to some extent. Results. Twenty-four trials were included in the review, of which 12 trials provided detailed data for meta-analyses. Preliminary evidence indicates that compared to wait list/sham group, acupuncture was effective on increasing paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Compared to medicine, acupuncture was less effective on PWT, but as effective as medicine on PWL. Acupuncture can reinforce medicine’s effect on PWT and PWL. Compared to the control group, acupuncture was superior to increase body weight (BW), decrease spinal cord glial fibrillary acidic protein (GFAP), and interleukin-1β (IL-1β). Furthermore, some studies showed acupuncture delay or partially reverse morphine tolerance. Three studies found acupuncture has no effect on PWT, but 2 of them found acupuncture could enhance small dose of Celebrex’s effect on CIBP. Conclusions. Acupuncture was superior to wait list/sham acupuncture on increasing PWT and has no less effect on increasing PWL compared to medicine; acupuncture improved the efficacy of drugs, increased the CIBP animals’ body weight, and decreased their spinal cord GFAP and IL-1β. High-quality studies are necessary to confirm the results.

Background: The clear understanding of the underlying mechanism of Osteoarthritis(OA) remains elusive.Researches have shown that Vascular Endothelial Growth Factor(VEGF) induced angiogenesis and inflammation were important processes in the pathophysiology of OA.Now, Anterior Cruciate Ligament Transection surgery(ACLT) induced OA model was often used to invesgate the molecular mechanism of OA,but till now the angiogenesis and inflammation reaction in different pathological stages of ACLT-induced OA model has never been revealed.Methods:Moderate OA 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,new blood vessel labeled by CD31 can been 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:VEGF-A related signaling pathway played an irreplaceable role in the occurrence and development of ACLT model,and the underlying mechanism may be related to the angiogenesis and inflammation in cartilage.

Background Knee Osteoarthritis (KOA) is one of the main causes of disability in the elderly and with limited treatment options. Swimming was considered as an ideal form of non-surgical management of KOA. Nevertheless, the mechanism of swimming intervene OA remains unclear. ACLT induced OA model was often used to study the pathogenesis and treatment of OA. Thus, we evaluated the protective effect of swimming on KOA mouse and tried to explore the underlying mechanism. Methods Forty C57BL/6 mice were randomly divided into five groups: Blank group, ACLT group, ACLT + Swim group, Sham group and Sham + Swim group (n = 8). OA model was established by Anterior Cruciate Ligament Transection surgery (ACLT). After modeling, mice in ACLT + Swim and Sham + Swim groups were trained with a moderate swimming program, 5 d/week, for 6 weeks. HE and Safranin-O/fast staining, Immunohistochemistry, TUNEL assay and Western blot were used to detect the effect of swimming on pathological changes, cell death and the mechanism in KOA mouse. Results Swimming significantly enhanced CoII expression and suppressed ADAMTS5 expression in cartilage of KOA mouse, thus ameliorated KOA development. Apoptotic and autophagic processes were enhanced in OA cartilage, which might be caused by down-regulation of PI3K/AKT pathway; swimming could activate PI3K/AKT pathway and thus regulate apoptosis and autophagy processes of chondrocytes. Conclusion Swimming could prevent cell death of chondrocytes via PI3K/AKT pathways, thus delayed the progression of KOA in an experimental model.