ObjectiveTo review and summarize the role and progress of innate immunity in the pathogenesis of osteoarthritis (OA).MethodsThe domestic and foreign literature in recent years was reviewed. The role of innate immune-mediated inflammation, macrophages, T cells, and complement systems in the pathogenesis of OA, potential therapeutic targets, and the latest research progress were summarized.ResultsWith the deepening of research, OA is gradually considered as a low-grade inflammation, in which innate immunity plays an important role. The polarization of synovial macrophage subpopulation in OA has been studied extensively. Current data shows that the failure of transformation from M1 subtype to M2 subtype is a key link in the progression of OA. T cells and complement system are also involved in the pathological process of OA.ConclusionAt present, the role of innate immunity in the progress of OA has been played in the spotlight, whereas the specific mechanism has not been clear. The macrophage subtype polarization is a potential therapeutic target for early prevention and treatment of OA.
Objective To investigate the effect of sodium hyaluronate (SH) intra-articular injection on the treatment of knee osteoarthritis (OA), andto compare the contents of free radicals and inflammatory factors in joint fluids of pre-and pro-treatment as to explore the treatment mechanism of SH. Methods Ninety-two patients (111 knees) with mild(51)，moderate(35) and serious(25) knee OA were treated with intra-articular injections of SH (20 mg once a week for 5 weeks). According to Lysholm scoring, clinical signs such aspain, swelling,and the ability to walk, squat, run, go upstairs and downstairs were assessed before and after the treatment, and the contents of nitric oxide (NO), superoxide dismutase(SOD), malonic dialdehyde(MDA) and IL-1β、TNF-α in joint fluids from the OA joints before 1st,2nd, and 5th injection and 3 months after each injection were observed. Results All cases were followed up for 3 months. The improvements in the signs and function of knees were excellent in 42 knees, good in 38 knees, fair in 21 knees and poor in 10 knees, with 72.1% excellent and good results. The lighter the illness was, the better the improvement was: the rate of the excellent and good was 92.1% in mild group, 68.6% in moderate group and 42.9% in serious group. The contents of oxygen free radicals and IL-1β、TNF-α of the patients with mild and moderate OA decreasedmarkedly after being treated with SH（Plt;0.05）, but these decreased lightlyin serious OA group（Pgt;0.05）. SH had mild effect on the contents of NO. Three months after treatment, only in mild OA group the contents of NO significantly decreased（Plt;0.05）, and no significant change in moderate and serious groups was observed（Pgt;0.05）. Conclusion SH intraarticular injection has a positive effect on the relief of clinical symptoms and on the improvement of articular function of knee OA. The therapeutical effect of SH on OA is achieved possibly by decreasing the contents of free radicals especially oxygen free radicals and inflammatory factors in joint fluids.
Objective To examine the effects of alendronate (ALN) on IL-1β-stimulated chondrocyte of rabbit in vitro and on cartilage and subchondral bone in rabbit osteoarthritis (OA) induced by anterior cruciate l igament transection (ACLT). Methods The chondrocytes from articular surface of healthy 3-month-old Japanese White rabbits were obtained by the method of enzyme digestion and cultured in vitro. The third generation chondrocytes were assigned into three groups: thechondrocytes were cultured in DMEM medium with 10 ng/mL IL-1β for 2 days, subsequently with (ALN group, group A1) orwithout (IL-1β group, group B1) 1 × 10-6 mol/L ALN for 3 days; the chondrocytes in vacant group (group C1) were cultured in DMEM medium for 5 days. The expression of Col II and MMP-13 were analyzed by immunocytochemical staining observation and real time RT-PCR test. Another twenty-four 3-month-old male Japanese White rabbits were randomized into three groups (n=8 per group). The OA model was made by ACLT in ACLT+ALN group (group A2) and ACLT group (group B2); the joint cave was sutured after exposure of ACL in sham group (group C2). After 4 days, the rabbits of group A2 received the subcutaneous injection of ALN at a dosage of 10 μg/(kg·d) for 8 weeks. Rabbits of group B2 and C2 received equal normal sal ine treatment. After 8 weeks, the rabbits were executed. The macro-pathologic changes of right knee joints were observed, so were the histological changes of femoral condyles. Expression levels of Col II and MMP-13 were detected by immunohistochemical staining. The bone histomorphometry analysis was appl ied to subchondral bone of proximal tibia. Results In vitro, the Col II immunocytochemical staining showed intensely positive staining in group C1, and the intensity of staining was sl ightly decreased in group A1, but the intensity of Col II immunocytochemical staining was extremely lower in the group B1. The integrated absorbance (IA) value for Col II in group A1 was significantly higher than that of group B1 (P lt; 0.05), but there was no significant difference between group A1 and group C1 (P gt; 0.05). Immunocytochemical detection of MMP-13 showed intense staining in group B1, and the intensity of staining was sl ightly decreased in group A1, but no MMP-13 expression was detected in the group C1. The IA value for MMP-13 in group A1 was significantly lower than that of group B1 (P lt; 0.05), but significantly higher than that of group C1 (P lt; 0.05). The real time RT-PCR analysis showed significantly higher mRNA levels of Col II in group A1 than in group B1 (P lt; 0.05), but there was no significant difference between group A1 and group C1 (P gt; 0.05). The MMP-13 mRNA level of the chondrocytes in group A1 was significantly lower than that of group B1 (P lt; 0.05), but significantly higher than that of group C1 (P lt; 0.05). In vivo, the gross appearance of surface of knee joint showed that there was no ulcer in group C2, and there was some ulcers in group A2, but many and all layers ulcers in group B2. Mankin score of group A2 was significantly lowerthan that of group B2 (P lt; 0.05), but significantly higher than that of group C2 (P lt; 0.05). Immunohistochemical staining showed that Col II in articular cartilage was intensely staining in group C2, the intensity of staining was sl ightly decreased in group A2, and the intensity of Col II immunohistochemical staining was extremely low in group B2, but there was no significant difference between group A2 and group C2 (P gt; 0.05..........
Objective To assess the effect of medial distal femoral osteotomy combined with interlocking nailing on the treatment of knee osteoarthritis with valgus deformity. Methods From May 1996 toAugust 2000, 16 patients with knee osteoarthritis accompanied by valgus deformity were treated by medial wedged distal femoral osteotomy combined with interlocking nailing. Full-length radiographs were taken before operation and 8 weeks and 2 years after operation. The parameters, including the femorotibial angle, the tibial angle, the femoral angle, the femoral condyletibial plateau angle, and the lateral joint space, were measured by these radiographs. The function of knee was evaluated by the 100 point rating scale standard of knee. Results The mean postoperative score was significantly improved from 50.4±15.9 points to 78.5±12.9 points 2 years after the surgery. The lateraljoint space was increased from 2.1±1.8 mm to 4.7±1.7 mm and the femoral condyletibial angle decreased from 5.6±2.9° to 1.6±3.4°. There were complications in 2 cases: 1 case of delayed union and 1 case of superficial wound infection. Conclusion Medial distal femoral osteotomy combined with interlocking nailing proves to be an effective approach to treat knee osteoarthritis with valgus deformity.
ObjectiveTo evaluate the efficacy and safety of glucosamine hydrochloride in the treatment of osteoarthritis. MethodsA total of 150 patients with osteoarthritis treated between April 2014 and April 2015 were randomly divided into control group and trial group with 75 in each. Patients in the trial group accepted oral glucosamine hydrochloride, while those in the control group were given diclofenac sodium. Lequesne index, total effective rate and the incidence of adverse reactions of both groups were calculated before and 2, 4, 6 and 8 weeks after treatment, and 2 weeks after drug withdrawal. ResultsIn both groups, Lequesne index started to decrease after 2 weeks of treatment (P<0.05), and reached the minimum value at treatment week eight (P<0.05). The Lequesne index 2 weeks after drug withdrawal was still obviously lower than that before treatment (P<0.05). There was no significant differences in the total effective rate at treatment week eight (83.1% for the control group and 80.9% for the trial group) or the total effective rate 2 weeks after drug withdrawal (80.0% for the control group and 79.4% for the trial group) between the control group and the trial group (P>0.05). The incidence of adverse reactions of the trial group (6.7%) was significantly lower than that of the control group (21.3%) (P<0.05). ConclusionGlucosamine hydrochloride is effective and safe in the treatment of osteoarthritis, which is suitable for long-term treatment.
ObjectiveTo detect the metabolites of the serum and joint fluid from rabbits’ osteoarthritis model with 1H nuclear magnetic resonance spectroscopy (NMR) technique, study the metabolic differences and connections of serum, synovial and cartilage of rabbits after the articular cavity injection of sodium hyaluronate, and explore osteoarthritis and metabolic mechanism in the process of treating sodium hyaluronate using sodium hyaluronate, thus provide new ideas and basis of the specific mechanisms in the treatment of osteoarthritis via sodium hyaluronate.MethodsWe selected 30 healthy New Zealand white rabbits, 6 months old, and randomly divided them into three groups as follows: blank control group, model phosphate buffer saline (PBS) liquid injection group and model injection of sodium hyaluronate group, with 10 rabbits in each group. Ten weeks after surgery, all experimental animals were put to death and observed in correlation studies regarding general condition, imaging examination, and histological examination. Metabolites 1H NMR detection and data preprocessing were performed in the serum and joint fluid samples.ResultsThe results considering general condition, general sample observation, imaging examination and histology indicated advantages in sodium hyaluronate group over PBS group. Metabolomics analysis showed statistically significant changes of metabolites in the serum and joint fluid compared with the PBS group and the blank control group (P<0.05). According to the relevant ways of differences metabolites retrieval, analysis found that the effect of sodium hyaluronate on osteoarthritis might be related to protein biosynthesis, amino acid circulation, the metabolic process of pyruvic acid, gluconeogenesis and other metabolic pathways.ConclusionsBased on the research of 1H-NMR metabolomics, the results suggest that the effect of sodium hyaluronate on osteoarthritis is mainly related with the activation of protein metabolism, abnormal lipid and energy metabolic pathways. This study provides new ideas and basis on the concrete mechanism in the treatment of knee osteoarthritis using sodium hyaluronate.
Objective To investigate the influence on matrix metalloproteinases (MMP) 3, 9, and 13 levels of human articular cartilage cells after blocking stromal cell derived factor 1 (SDF-1)/ chemokine receptor 4 (CXCR4) signaling pathway withAMD3100 and to define the function mechanism of AMD3100. Methods A total of 144 cartilage blocks from 12 osteoarthritis (OA) patients undergoing total knee arthroplasty (OA cartilage group) and 144 normal cartilage blocks (Mankin score of 0 or 1) from 12 patients undergoing traumatic amputation (normal cartilage group). OA cartilage group was further divided into subgroups A1, B1, and C1, and normal cartilage group into subgroups A2, B2, and C2. The cartilage tissues were cultured in DMEM solution containing 100 ng/mL SDF-1 and 1 000 nmol/L AMD3100 in subgroup A, 100 ng/mL SDF-1 and 1 000 nmol/L MAB310 in subgroup B, and 100 ng/mL SDF-1 in subgroup C, respectively. The levels of MMP-3, 9, and 13 were measured by ELISA; the expressions of MMP-3, 9, and 13mRNA were tested by RT-PCR. Results ELISA and RT-PCR results showed that the levels of MMP-3, 9, and 13 and the expressions of MMP-3, 9, and 13 mRNA were significantly lower in subgroup A than in subgroups B and C at the same time points (P lt; 0.05); the levels of MMP-3, 9, and 13 and the expressions of MMP-3, 9, and 13 mRNA were significantly higher in OA cartilage group than in normal cartilage group at the same time points (P lt; 0.05). Conclusion SDF-1 could induce overexpression and release of MMP-3, 9, and 13 in the articular cartilage through the SDF-1/CXCR4 signaling pathway; AMD3100 could reduce the mRNA expressions and secretion of MMP-3, 9, and 13 in OA cartilage by blocking the SDF-1/CXCR4 signaling pathway; but AMD3100 could not make the secretion of MMP-3, 9, and 13 return to normal levels in OA cartilage.
ObjectiveTo compare the clinical efficacy of glucosamine hydrochloride and diacerein for patients with knee osteoarthritis and the MRI variation. MethodsBetween January and June 2014, 90 patients with knee osteoarthritis were randomized into three groups: group A (treated by glucosamine hydrochloride), group B (treated by diacerein) and group C (treated by both glucosamine hydrochloride and diacerein). The score of Western Ontario and McMaster Universities (WOMAC) index of osteoarthritis, MRI cartilage injury Recht grading and the curative effects for bone marrow edema, joint cavity effusion and meniscus injury were compared before and after the treatment. ResultsThe scores of WOMAC after treatment in all the groups were improved, while the therapeutic effect of group C lasted longer when medical treatment suspended. The number of articular surface with different degrees of cartilage injury showed no statistically significant change in all three groups (P ＞ 0.05) . The state of bone marrow edema and joint cavity effusion were improved with a statistically significant difference in all groups (P ＜ 0.05) . Patients with lateral meniscus degeneration in group A and patients with medial meniscal tear in group B both increased with statistically significant differences (P ＜ 0.05) . However, in group C, patients with lateral meniscus degeneration or meniscal tear decreased with statistically significant differences (P ＜ 0.05) . ConclusionsThe treatment for osteoarthritis by glucosamine hydrochloride is effective, and the curative effect lasts longer when treated by both glucosamine hydrochloride and diacerein. Glucosamine hydrochloride ameliorates the bone marrow edema and joint cavity effusion. Treatment together with diacerein leads to a better therapeutic effect for patients with meniscus degeneration, yet further studies are needed to prove its effects in ameliorating cartilage injury.
Objective To investigate the feasibil ity of alendronate (ALN) in treating osteoarthritis (OA) by observing the effects of ALN on interleukin 1β (IL-1β) induced chondrocytes of rat in vitro. Methods The chondrocytes of knee articular surface from 15 SD rats (1-month-old, female or male, weighing 100-150 g) were cultured. The chondrocytes were observed by inverted phase contrast microscope and identified by toluidine blue staining and HE staining. The third passage chondrocytes were divided into 3 groups: the chondrocytes were cultured with DMEM for 5 days in group A, with 10 ng/mL IL-1β for 2 days and with DMEM for 3 days in group B, and with 10 ng/mL IL-1β for 2 days and with 1 × 10-6 mol/L ALN for 3 days in group C. Immunocytochemistry and real-time PCR were performed to determine the expression levels of collagen type II (Col II), matrix metalloproteinase 13 (MMP-13), and β-catenin. Results Toluidine blue staining proved that the cultured cells were chondrocytes. The integrated absorbency (IA) value of Col II in group C (10.290 7 ± 0.499 2) was lower than that in group A (15.377 0 ± 0.571 8) and higher than that in group B (5.463 2 ± 0.450 4), showing significant differences (P lt; 0.05). The IA value of MMP-13 in group C (3.068 6 ± 0.205 6) was significantly lower than that in group B (6.998 1 ± 0.329 7, P lt; 0.05), but there was no significant differenc when compared with group A (2.777 5 ± 0.199 6, P gt; 0.05). The IA value of β-catenin in group C (6.611 7 ± 0.381 8) was lower than that in group B (11.799 9 ± 0.348 7) and higher than that in group A (4.390 3 ± 0.551 9), showing significant differences (P lt; 0.05). The mRNA expression of Col II in group C was significantly higher than those in groups A and B (P lt; 0.05), the mRNA expression of MMP-13 in group C was significantly lower than that in group B (P lt; 0.05) but there was no significant difference when compared with group A (P gt; 0.05). The mRNA expression of β-catenin in group C was significantly lower than that in group B (P lt; 0.05) and higher than that in group A (P lt; 0.05). Conclusion ALN can protect rat chondrocyte from OA induced by IL-1β in vitro possibly by upregulating Col II and inhibiting the expression of MMP-13 and β-catenin in the chondrocytes.
Osteoarthritis is a common degenerative joint disease, which is often analyzed by X-ray images. However, if there is a lack of clinical experience when reading the films, it is easy to cause misdiagnosis. Although deep learning has made significant progress in the field of medical image processing, existing models still have limitations in capturing subtle lesion features such as joint spaces. This paper proposes an automatic diagnosis method for osteoarthritis based on the improved shifted windows Transformer (Swin Transformer) and graph convolutional network. By enhancing the modeling of joint space features and cross-layer feature fusion, it is expected to effectively improve the accuracy of early diagnosis of osteoarthritis. Firstly, this paper designs the shifted windows horizontal attention mechanism (SW-HAM), which can enhance the feature extraction ability in the horizontal direction. Secondly, the central-attention graphSAGE (CAG-SAGE) is introduced to conduct weighted aggregation of the feature information of the lesion area through the dynamic attention mechanism. Finally, cross-layer connection technology is utilized to achieve efficient fusion of multi-layer features. The experimental results show that the SW-HAM and CAG-SAGE modules and cross-layer connections significantly improve the model performance. The classification accuracy, recall rate, precision rate, F1 score, and area under the curve are 94.59%, 95.14%, 94.05%, 94.41%, and 96.30% respectively, all of which are superior to the classical network and existing methods. It provides a new and effective method for the classification and diagnosis of osteoarthritis.