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In recent years, difficult-to-treat rheumatoid arthritis (D2T RA) has attracted significant attention from rheumatologists due to its poor treatment response and the persistent symptoms or signs experienced by patients. The therapeutic demands of patients with D2T RA are not properly met due to unclear pathogenic causes and a lack of high-quality data for current treatment options, creating considerable management difficulties with this patient population. This review describes the clinical challenges associated with disease-modifying antirheumatic drugs (DMARDs) and explores contributing factors associated with inappropriate response to DMARDs that may lead to D2T RA and related immunological dysregulation. It is now understood that D2T RA is a highly heterogeneous pathological status that involves multiple factors. These factors include but are not limited to genetics, environment, immunogenicity, comorbidities, adverse drug reactions, inappropriate drug application, poor adherence, and socioeconomic status. Besides, these factors may manifest in the selection and utilization of specific DMARDs, either individually or in combination, thereby contributing to inadequate treatment response. Finding these variables may offer hints for enhancing DMARD therapy plans and bettering the condition of D2T RA patients.

Asunto(s)

Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Humanos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico

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INTRODUCTION: Osteoporosis is related to lncRNA-neighboring enhancer of FOXA2 (NEF) and inversely correlated to ankylosing spondylitis (AS), implying that lncRNA-NEF might also relate to AS. Thus, the study was carried out to investigate the involvement of lncRNA-NEF in AS. METHODS: The study included 60 AS patients and 60 healthy controls. LncRNA-NEF expression in synovial fluid samples was analyzed by reverse transcription quantitative real-time polymerase chain reaction. Disease activity of the 60 AS patients was determined using the Ankylosing Spondylitis Disease Activity Score (ASDAS) 1-4 and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Western blot was carried out to investigate the effects of lncRNA-NEF on inflammatory factors in human fibroblast-like synovial (HFLS) cells. A 3-year follow-up was performed to analyze the role of lncRNA-NEF in the prediction of the recurrence of AS. RESULTS: Our study observed that lncRNA-NEF expression was upregulated in synovial fluid of AS patients and significantly correlated with the ASDAS 1-4, BASDAI, erythrocyte sedimentation rate (ESR), and C-reactive protein level (p < .05). Treatment with nonsteroidal anti-inflammatory drugs significantly downregulated lncRNA-NEF expression (p < .01). A 3-year follow-up showed that patients with high lncRNA-NEF levels had a high recurrence rate (hazard ratio = 2.266). In addition, lncRNA-NEF was found to regulate the expression of inflammatory factors in HFLS cells. CONCLUSIONS: Therefore, lncRNA-NEF upregulation can predict recurrence and poor treatment outcomes of AS and has a great potential to serve as a predictive biomarker factor for the recurrent AS.

Asunto(s)

ARN Largo no Codificante , Espondilitis Anquilosante , Sedimentación Sanguínea , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/uso terapéutico , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/genética , Resultado del Tratamiento , Productos del Gen nef del Virus de la Inmunodeficiencia Humana/uso terapéutico

RESUMEN

BACKGROUND: Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease. Deficiency pattern (DP) and excess pattern (EP), as crucial types of Chinese medicine pattern diagnoses published by International Classification of Diseases 11th Revision (ICD-11), could provide new strategies for RA diagnosis. However, the biological basis of DP and EP of RA is not explicit. METHODS: 19 female RA DP patients, 41 female RA EP patients and 30 female healthy participants were included in the study. The serums of participants were collected and analyzed by metabolomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to profile metabolic characteristics of RA DP and EP. Furthermore, bioinformatics analysis results were obtained by using Ingenuity Pathway Analysis (IPA) and statistical analysis was performed by SAS version 9.4 for further identification of potential biomarkers. RESULTS: Serum metabolic profiling revealed 25 and 24 differential metabolites in RA DP and EP respectively, and 19 metabolites were common to RA DP and EP. Compared with DP group, L-Homocysteic acid, LysoPE(P-16:0/0:0), N(omega)-Hydroxyarginine and LysoPC(16:0/0:0) decreased (P < 0.05), and Pyruvic acid, D-Ribose, Gamma-Glutamylserine, PE(22:0/24:1(15Z)), Inosinic acid increased (P < 0.05) in EP group. Menawhile, S-Nitrosoglutathione, 5-Thymidylic acid, SN38 glucuronide, PE(22:0/24:0), PC(24:0/24:1(15Z)) and Bisdiphosphoinositol tetrakisphosphate increased significantly in DP group compared to EP group (P < 0.05). For the unique metabolites, bioinformatics analysis results showed that 5-Methoxytryptamine involved in Melatonin Degradation II and Superpathway of Melatonin Degradation is the key metabolite to RA DP. Meanwhile, GABA is the key metabolite in EP group, which involved in Glutamate Dependent Acid Resistance, GABA Receptor Signaling, Glutamate Degradation III (via 4-aminobutyrate) and 4-aminobutyrate Degradation I. Bioinformatics analysis between unique metabolites of RA DP and EP groups with human target genes for RA showed that 5-methoxytryptamine and LysoPC(18:1(9Z)/0:0), the unique metabolites of RA DP, might participate in colorectal cancer metastasis signaling, tumor microenvironment pathway, apoptosis signaling, MYC mediated apoptosis signaling, erythropoietin signaling pathway and LXR/RXR activation. Simultaneously, GABA, LysoPA(18:1(9Z)/0:0) and L-Targinine, the unique metabolites of RA EP, might participate in neuroinflammation signaling pathway, osteoarthritis pathway, glucocorticoid receptor signaling, ILK signaling, IL-17 signaling and HIF1α signaling. CONCLUSIONS: The study indicates that serum metabolomics preliminarily revealed the biological basis of RA DP and EP. 5-methoxytryptamine, LysoPC(18:1(9Z)/0:0) and GABA, LysoPA(18:1(9Z)/0:0), L-Targinine might be the predictors to distinguish the DP and EP of RA respectively. These interesting results provide thoughts for further study of traditional medicine patterns of ICD-11. It also contributes to provide strategy for personalized precision treatment of RA and further validation is needed.

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Objective: This study aimed to systematically review the efficacy and clinical safety of different courses and doses of tripterygium glycoside (TG) adjuvant methotrexate (MTX) therapy in the treatment of rheumatoid arthritis (RA). Methods: Randomized controlled trials (RCTs) of TG adjuvant MTX therapy in patients with RA were retrieved from SinoMed, China Network Knowledge Infrastructure, WanFang Data, PubMed, Cochrane Library, and Embase from inception to September 30, 2021. The effects and clinical safety evaluations were conducted using RevMan 5.3 software. Results: A total of 9 RCTs and 892 patients with RA were included in this study. In the meta-analysis, a total of 463 and 429 patients were enrolled into the TG adjuvant MTX therapy group and MTX monotherapy group, respectively. In comparison with MTX monotherapy, the results of the analyzed effects showed that the TG adjuvant MTX therapy can achieve 20%, 50%, and 70% improvements in American College of Rheumatology (ACR) criteria ACR20, ACR50, and ACR70 at P = 0.005, P = 0.0001, and P = 0.004, respectively. Simultaneously, the efficacy of the TG adjuvant MTX therapy was improved at either 30 or 60 mg/day over a six-month course compared to MTX monotherapy (P < 0.0001). There was no statistical difference in the effects between the doses of 30 and 60 mg/day after three months (P = 0.82). TG adjuvant MTX also reduced the expression rate of the swollen joint count, tender joint count, erythrocyte sedimentation rate, rheumatoid factor, and C-reactive protein in subgroup analyses with different courses and doses. In terms of hepatic adverse effects (P = 0.28), leukopenia (P = 0.78), gastrointestinal adverse effects (P = 0.17), cutaneous adverse effects (P = 0.94), and irregular menstruation adverse effects (P = 0.29), there was no statistically significant difference with TG adjuvant MTX therapy and MTX monotherapy with different courses and doses. Conclusions: TG adjuvant MTX therapy is more effective than MTX monotherapy and is a safe strategy for RA treatment in doses of 30 or 60 mg/day over a treatment course of six months. However, high-quality multicenter RCT studies with large sample sizes are still needed to confirm the effects and clinical safety of different courses and doses of TG adjuvant MTX therapy.

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BACKGROUND: Secondary osteoporosis may occur in patients with rheumatoid arthritis (RA), causing irreversible joint damage and disability. Bisphosphonates, the recently developed bone resorption inhibitors, have demonstrated significant therapeutic effects on senile and postmenopausal osteoporosis. This study evaluated the efficacy and safety of zoledronic acid (ZOL), with or without methotrexate (MTX), for the prevention and treatment of bone destruction in RA patients. METHODS: We recruited 66 RA patients with symptoms of secondary osteoporosis. They were randomized into three treatment groups-combined treatment with MTX and ZOL, ZOL monotherapy, or MTX monotherapy-in two consecutive 6-month periods. The participants were followed for 12 months. At the end of each treatment period, improvement in disease activity, bone destruction, and fracture risk were evaluated. RESULTS: Combined treatment with ZOL and MTX had significantly better clinical efficacy compared with either ZOL or MTX monotherapy (P < 0.05). The combination significantly improved the lumbar spine and hip BMD and reduced FRAX scores, suggesting that ZOL combined with MTX reduces bone loss and risk of hip fracture in RA patients with secondary osteoporosis. CONCLUSION: ZOL has a synergistic effect when combined with MTX, inhibiting RA disease activity, reducing fracture risk, and improving quality of life in RA patients with secondary osteoporosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800019290. Registered 3 November 2018-Retrospective registered, http://www.chictr.org.cn/showproj.aspx?proj = 31758.

Asunto(s)

Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Conservadores de la Densidad Ósea/uso terapéutico , Osteoporosis/diagnóstico por imagen , Osteoporosis/tratamiento farmacológico , Ácido Zoledrónico/uso terapéutico , Artritis Reumatoide/complicaciones , Densidad Ósea/efectos de los fármacos , Densidad Ósea/fisiología , Conservadores de la Densidad Ósea/farmacología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/etiología , Ácido Zoledrónico/farmacología

RESUMEN

BACKGROUND: Data on indication of Unicompartmental Knee Arthroplasty (UKA) in the Asian population are currently not available. The current paper evaluates patients undergoing knee replacement at a Chinese Orthopaedic Specialty Hospital to report the percentage of patients who meet radiographic and clinical indication criteria for UKA. METHODS: Over a one-year period 463 consecutive patients (515 knees) underwent primary knee replacement surgery. Clinical data were recorded and preoperative radiographs were assessed. Patients were classified as suitable candidates for UKA based on the degree of deformity, preoperative ROM and radiographic appearance of osteoarthritis. The different indication criteria for body weight and extend of patellofemoral osteoarthritis as reported by Kozinn and Scott as well as the Oxford Group were applied. RESULTS: 160 knees (31%) were excluded because of inflammatory and posttraumatic arthritis. 55 knees had to be excluded because of incomplete radiographs. Of the remaining 300 knees with osteoarthritis, 241 knees were excluded because of extend of deformity (n=156), decreased range of motion (n=119), advanced patellofemoral arthritis with bone loss (n=11) and AP instability (n=1). Of the remaining 63 knees, 54 knees (18%) met the modified Oxford criteria for mobile UKA and only 25 knees (8%) met the Scott and Kozinn criteria for fixed UKA. CONCLUSION: The current paper suggests that in comparison to Caucasian population, only a smaller percentage of patients at a Chinese Orthopaedic Specialty Hospital meet the indication criteria for UKA. Therefore, it might make sense to concentrate UKA surgeries in high volume centers.

RESUMEN

OBJECTIVE: To compare therapeutic effects between the normal rehabilitation and combined with manipulative method after arthroscopic capsular release for the treatment of severe frozen shoulder, and to evaluate the application value of manipulationp. METHODS: From March 2007 to July 2010,arthroscopic capsular release was performed in 48 cases (48 shoulders, 23 left side, 25 right side). All the patients were divided into two groups: control group (11 males and 15 females) and manipulation group (9 males and 13 females). The patients in the control group were treated with conventional rehabilitation procedure, and the patients in the manipulation group were treated with additional manipulation procedure. From the 2nd day after operation, the manipulation was performed for 20 minutes every time, twice daily, and it continued for 10 days. All the cases were followed up and the scale of American Shoulder and Elbow Surgeons Standardized Assessment Form (ASES self-report section) and the range of motion (ROM) were recorded. RESULTS: The mean follow-up period was (12.54 +/- 5.78) months (ranging from 4 to 25 months). Both ASES scores and ROM in the manipulation group were better than those in the control group at the 1st month after operation, and the difference between the ASES scores and flexion of the shoulder were significant. However, there was no significan difference at the latest follow-up. CONCLUSION: Compared with the conventional rehabilitative procedure, manipulation following arthroscopic capsular release could promote the process of joint rehabilitation and help the patient back to normal life earlier, but there is no evidence of long term advantage.

Asunto(s)

Bursitis/cirugía , Bursitis/terapia , Liberación de la Cápsula Articular , Manipulaciones Musculoesqueléticas , Artroscopía , Bursitis/fisiopatología , Estudios de Casos y Controles , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular , Resultado del Tratamiento

RESUMEN

OBJECTIVE: Through establishing the rat model of CIA to evaluate the effect and mechanism of Rhizoma Drynariae Flavone on bone destruction of CIA rat. METHODS: Subcutaneous injection of bovine type II collagen was used to induce Wistar rats to fall ill, and then established the rat model of CIA. The rats whose inflammation scores reached to two points or above were randomly divided into four groups, and were treated accordingly. The effect of Rhizoma Drynariae Flavone on bone destruction was evaluated. RESULTS: At 12 weeks after treatment, bone trabecular area percentage and bone trabecular number in Rhizoma Drynariae Flavone group, Rhizoma Drynariae Flavone-1/2 Etanercept group, Etanercept group was obviously higher than that of sterilization water group (P < 0.05); and the trabecular resolving power of these groups was obviously less than that of sterilization water group (P < 0.05). CONCLUSION: Rhizoma Drynariae Flavone can obviously inhibit inflammation of joint bone destruction of CIA rats,the effect may be related with bone trabecular number reduction and trabecular resolving power increasing.

Asunto(s)

Artritis Experimental/tratamiento farmacológico , Flavonas/uso terapéutico , Polypodiaceae/química , Animales , Artritis Experimental/patología , Huesos/patología , Femenino , Ratas , Ratas Wistar

RESUMEN

OBJECTIVE: To evaluate the outcomes of primary total knee arthroplasty (TKA) in the treatment of knee with severe lateral instability and summarize the essential points of operation and rehabilitation. METHODS: From February 2005 to August 2010, primary TKA was performed in 27 severe lateral unstable knees (25 cases), including 3 males (3 knees) and 22 females (24 knees). Their mean age was 57.8 (37-71) years. And their primary diseases included rheumatoid arthritis (22 knees in 21 cases) and osteoarthritis (5 knees in 4 cases). Thirteen lateral unstable knees were accompanied with 18.08° ± 5.96°(15-35°) varus deformity; in the rest 14 knees, there was medial instability with 20.71° ± 7.03° (15-35°) valgus deformity. Blood loss volume, operative duration and complications were recorded. During the follow-up period, HSS score, knee stability and varus/valgus status were recorded preoperatively, 1, 3, 6, 12 months and then annually postoperatively. RESULTS: AORI type I bone defect was found at the proximal tibia in 18 knees and distal lateral femoral condyle in 10 knees. All defects were reconstructed with cement or autograft. AORI type II bone defects at proximal tibia in 3 knees were reconstructed with metal augmentation. Blood loss during the first 24 hours were (438.9 ± 109.5) (400-700) ml and operative duration (91.1 ± 11.6) (70-110) min. The mean follow-up period was (41.6 ± 10.9) (27-60) months. At the final follow-up, the HSS score increased from (45.8 ± 5.4) to (85.4 ± 4.5) (t = 30.15, P < 0.01) .Five knees in 5 cases had mild postoperative instability. All cases were allowed to walk with knee orthosis for 4-6 weeks. At the end of follow-up, mild lateral instability of 2 knees persisted. One augmented knee had osteolysis beneath metal block. CONCLUSION: TKA for knees with severe lateral instability requires a deep understanding of causes and a rational treatment. Proper handling of bone defects and careful release of lateral soft tissue are two critical points for postoperative knee stability. Wearing knee orthosis during the early postoperative stage may be helpful or residual mild instability.

Asunto(s)

Artroplastia de Reemplazo de Rodilla , Inestabilidad de la Articulación/cirugía , Articulación de la Rodilla , Adulto , Anciano , Femenino , Humanos , Prótesis de la Rodilla , Masculino , Persona de Mediana Edad , Resultado del Tratamiento

RESUMEN

BACKGROUND: Rheumatoid arthritis (RA) is a kind of chronic autoimmune disease and osteoporosis is one of its complications. OBJECTIVE: To explore the effects of Qianggu Capsule, a compound traditional Chinese herbal medicine, on bone mineral density (BMD) and osteoporosis in patients with RA. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: Eighty-two patients with rheumatoid arthritis and osteoporosis, who were treated in Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine from January 2010 to December 2011, were divided into treatment group (42 cases) and control group (40 cases). The patients in the treatment group were administered with Qianggu Capsule and two disease-modifying antirheumatic drugs. The patients in the control group were administered with two common-used antirheumatic drugs. The course of treatment was 6 months. MAIN OUTCOME MEASURES: Blood levels of alkaline phosphatase (ALP), calcium, phosphorus, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were determined before and after the treatment. BMD in the lumbar spine, femur and the left distal radius were also examined before and after the treatment. RESULTS: The ALP level, a bone metabolic parameter, was significantly increased in patients of the treatment group after treatment compared with before treatment. BMD values in the lumbar spine, femur and the radius were higher after treatment than before treatment (P<0.05). There were no changes in ALP level and BMD in the patients of the control group after the treatment when compared with before treatment. CONCLUSION: Treatment with Qianggu Capsule can increase BMD of RA patients, and then ameliorate their osteoporosis.

Asunto(s)

Artritis Reumatoide/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Osteoporosis/tratamiento farmacológico , Adulto , Fosfatasa Alcalina/sangre , Artritis Reumatoide/complicaciones , Densidad Ósea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/etiología

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BACKGROUND: Total knee replacement surgery is commonly used in end-stage diseases of the knee. It is important for improving surgical efficacy and patient satisfaction by promoting early rehabilitation of patients and improving knee function. OBJECTIVE: To observe the effects of early application of Tuina treatment on quadriceps surface electromyography (EMG) in patients with rheumatoid arthritis having undergone total knee arthroplasty. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: The study was performed at the Orthopedic Department of Huashan Hospital, Fudan University, and the Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine from June 2010 to September 2011. A total of 66 patients with rheumatoid arthritis who had undergone total knee replacement surgery were randomly divided into control group and observation group, 33 cases in each. The patients in the control group were administered with continuous passive training (CPM), and the patients in the observation group were treated with CPM combined with Tuina, from prior surgery to four weeks post-surgery. MAIN OUTCOME MEASURES: The knee function was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire at baseline and 4 weeks after the surgery. Quadriceps surface EMG was also detected at the same time points. RESULTS: After 4 weeks of Tuina and comprehensive rehabilitation intervention, the WOMAC questionnaire score of the observation group was decreased compared with the control group (P<0.01); median frequency and integrated electromyography of the rectus femoris and vastus medialis muscles, which were recorded by EMG, in the observation group were higher than those in the control group (P<0.01). CONCLUSION: Tuina can improve the recovery of patients who have undergone total knee replacement by increasing quadriceps EMG.

Asunto(s)

Medicina Tradicional China , Manipulaciones Musculoesqueléticas , Músculo Cuádriceps/fisiopatología , Anciano , Artroplastia de Reemplazo de Rodilla , Electromiografía , Femenino , Humanos , Persona de Mediana Edad , Periodo Posoperatorio

RESUMEN

Cysteine-rich protein 61 (Cyr61)/CCN1 is a product of an immediate early gene and functions in mediating cell adhesion and inducing cell migration. We previously showed that increased production of Cyr61 by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) promotes FLS proliferation and participates in RA pathogenesis with the IL-17-dependent pathway. However, whether Cyr61 in turn regulates Th17 cell differentiation and further enhances inflammation of RA remained unknown. In the current study, we explored the potential role of Cyr61 as a proinflammatory factor in RA pathogenesis. We found that Cyr61 treatment dramatically induced IL-6 production in FLS isolated from RA patients. Moreover, IL-6 production was attenuated by Cyr61 knockdown in FLS. Mechanistically, we showed that Cyr61 activated IL-6 production via the αvß5/Akt/NF-κB signaling pathway. Further, using a coculture system consisting of purified CD4(+) T cells and RA FLS, we found that RA FLS stimulated Th17 differentiation, and the pro-Th17 differentiation effect of RA FLS can be attenuated or stimulated by Cyr61 RNA interference or addition of exogenous Cyr61, respectively. Finally, using the collagen-induced arthritis animal model, we showed that treatment with the anti-Cyr61 mAb led to reduction of IL-6 levels, decrease of Th17 response, and attenuation of inflammation and disease progression in vivo. Taken together, our results reveal a novel role of Cyr61 in promoting Th17 development in RA via upregulation of IL-6 production by FLS, thus adding a new layer into the functional interplay between FLS and Th17 in RA pathogenesis. Our study also suggests that targeting of Cyr61 may represent a novel strategy in RA treatment.

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Artritis Reumatoide/inmunología , Diferenciación Celular/inmunología , Proteína 61 Rica en Cisteína/fisiología , Fibroblastos/inmunología , Interleucina-6/biosíntesis , Membrana Sinovial/inmunología , Células Th17/inmunología , Adulto , Anciano , Animales , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Células Cultivadas , Técnicas de Cocultivo , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Interleucina-6/fisiología , Masculino , Ratones , Ratones Endogámicos DBA , Persona de Mediana Edad , Receptores de Vitronectina/fisiología , Transducción de Señal/inmunología , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Células Th17/patología

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OBJECTIVE: To observe the effects of Bushen Qianggu decoction proliferation and PCNA and Bcl-2 expression. METHODS: Serum containing BQD was made and synovial fibroblasts were separated and cultured and passaged in vitro. Four groups were divided as 20% blank control group, serum containing 20% Tripterygium wilfordii multi-glycosides drug (TWMD), 20% of serum containing high and low of BQD, respectively. Serum containing drugs of different concentration were added into the synovial fibroblasts of the third generation, and then the synovial fibroblasts were cultured continued. The effects of different drugs on synovial fibroblasts and PCNA and Bcl-2 expression were observed. RESULTS: Compared with the control serum, BQD-containing serum promoted the apoptosis of synovial fibroblasts (P < 0.000 1); especially, high dose could inhibit proliferation. The expression of PCNA and Bcl-2 was significantly lower in BQD-containing serum (P < 0.000 1 vs control group). CONCLUSION: BQD can promote the apoptosis of synovial fibroblasts by improving of expression of PCNA and Bcl-2, which may be one of the mechanisms of BQD in preventing and treating osteoporosis of rheumatoid arthritis.

Asunto(s)

Medicamentos Herbarios Chinos/farmacología , Antígeno Nuclear de Célula en Proliferación/análisis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Membrana Sinovial/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Ratas , Ratas Wistar , Membrana Sinovial/química , Membrana Sinovial/citología

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Total glucoside of paeony (TGP), an active compound extracted from paeony root, has been used in therapy for rheumatoid arthritis (RA). Th1 and Th17 cells are now believed to play crucial roles in the lesions of RA. However, the molecular mechanism of TGP in inhibition of Th1 and Th17 cells remains unclear. In this study, we found that TGP treatment significantly decreased percentage and number of Th1 and Th17 cells in collagen induced arthritis (CIA) mice. Consistently, treatment with TGP decreased expression of T-bet and RORγt as well as phosphorylation of STAT1 and STAT3. In particular, TGP treatment inhibited dendritic cells (DCs) maturation and reduced production of IL-12 and IL-6. Moreover, TGP-treatment RA patients showed shank population of matured DCs and IFN-γ-, IL-17-producing cells. Taken together, our results demonstrated that TGP inhibited maturation and activation of DCs, which led to impaired Th1 and Th17 differentiation in vivo.

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Artritis Reumatoide/tratamiento farmacológico , Células Dendríticas/efectos de los fármacos , Glucósidos/farmacología , Paeonia/química , Células TH1/efectos de los fármacos , Células Th17/efectos de los fármacos , Adulto , Anciano , Animales , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Artritis Reumatoide/inmunología , Artritis Reumatoide/metabolismo , Células Dendríticas/inmunología , Femenino , Humanos , Interleucina-12/biosíntesis , Interleucina-6/biosíntesis , Masculino , Ratones , Ratones Endogámicos DBA , Persona de Mediana Edad , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/metabolismo

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Fixed versus rotating-platform knee arthroplasty for total knee arthroplasty is still a controversial topic. In this article, biomechanical and clinical aspects of rotating-platform knee arthroplasty are reviewed. In regard to its biomechanical characteristics, the rotating-platform knee arthroplasty design has been proved to provide less tibiofemoral contact stress under conditions of tibiofemoral malalignment. It also reduces the wear rate. However, in regard to its clinical characteristics, the mid-term and long-term survivorship of rotating-platform knee arthroplasties is not superior to that of fixed-platform knees. It appears that we are at a crossroads. In this article, progress in biomechanical and clinical aspects of rotating-platform knee prosthesis is reviewed.

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Artroplastia de Reemplazo de Rodilla/métodos , Prótesis de la Rodilla , Diseño de Prótesis/métodos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Falla de Prótesis , Rango del Movimiento Articular/fisiología , Recuperación de la Función , Medición de Riesgo , Resultado del Tratamiento

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OBJECTIVE: To evaluate the efficacy of Tuina and Chinese patent drug Shuxuetong injection in preventing patients undergoing total knee arthroplasty from deep venous thrombosis and in functional rehabilitation. METHODS: A total of 120 patients with diagnosed rheumatoid arthritis in the Department of Orthopaedic Surgery, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine in China were enrolled for this study. The patients underwent total knee arthroplasty and were divided into treatment group (n=60) and control group (n=60) after surgery. Patients in the control group received conventional rehabilitation training, including using a continuous passive motion machine and training of muscle contractions of the lower limb. Patients in the treatment group were administered Shuxuetong injection and Tuina based on the conventional rehabilitation training. The course of treatment lasted for 2 weeks. Hospital for Special Surgery (HSS) knee score, rate of deep venous thrombosis and range of motion of the knee joint were evaluated before and after treatment. RESULTS: There was no significant difference in HSS knee score and range of motion as compared before and after treatment in two group (P>0.05). The rate of deep venous thrombosis of the treatment group was 13.33%, which was lower than 20% of the control group (P<0.05). CONCLUSION: Tuina combined with Shuxuetong injection treatment can prevent deep venous thrombosis in patients with rheumatoid arthritis after total knee arthroplasty.

Asunto(s)

Artroplastia de Reemplazo de Rodilla/rehabilitación , Medicamentos Herbarios Chinos/uso terapéutico , Manipulaciones Musculoesqueléticas/métodos , Fitoterapia , Trombosis de la Vena/prevención & control , Adulto , Femenino , Humanos , Articulación de la Rodilla , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Rango del Movimiento Articular

RESUMEN

OBJECTIVE: Fibroblast-like synoviocytes (FLS) are a major component of the hyperplastic synovial pannus that aggressively invades cartilage and bone during the course of rheumatoid arthritis (RA). Cyr61 (CCN1) is a product of a growth factor-inducible immediate early gene and is involved in cell adhesion, proliferation, and differentiation. However, the role that Cyr61 plays in FLS proliferation has remained undetermined. The aim of this study was to identify the role of Cyr61 in regulating the proliferation of FLS derived from patients with RA. METHODS: Expression of Cyr61 in synovial tissue (ST) and in FLS was determined simultaneously using immunohistochemistry, real-time polymerase chain reaction, and Western blotting. Cyr61 levels in synovial fluid (SF) were determined by enzyme-linked immunosorbent assay. FLS proliferation stimulated by SF, Cyr61, and interleukin-17 (IL-17) was measured by thymidine incorporation. Activation of signal transduction pathways was determined by Western blotting and confocal microscopy. RESULTS: Cyr61 was overexpressed in ST, FLS, and SF samples from RA patients as compared with samples from normal controls. Elevated levels of Cyr61 in RA SF promoted the proliferation of FLS, an effect that was abrogated by a neutralizing monoclonal antibody against human Cyr61. Furthermore, in samples from RA patients, Cyr61 was found to protect FLS from apoptosis and to sustain the expression of Bcl-2 in FLS. Most importantly, the expression of Cyr61 in FLS was regulated by IL-17 mainly via the p38 MAPK and NF-kappaB signaling pathways. Knockdown of expression of the Cyr61 gene inhibited IL-17-stimulated FLS proliferation. CONCLUSION: Our findings indicate that Cyr61 plays a critical role in IL-17-mediated proliferation of FLS in RA and likely contributes to hyperplasia of synovial lining cells and eventually to joint destruction in patients with RA.

Asunto(s)

Artritis Reumatoide/metabolismo , Proteína 61 Rica en Cisteína/fisiología , Membrana Sinovial/metabolismo , Adulto , Anciano , Anticuerpos Neutralizantes/farmacología , Artritis Reumatoide/patología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Proteína 61 Rica en Cisteína/farmacología , Femenino , Regulación de la Expresión Génica , Silenciador del Gen , Humanos , Interleucina-17/farmacología , Masculino , Persona de Mediana Edad , Osteoartritis/metabolismo , Interferencia de ARN , Líquido Sinovial/metabolismo , Membrana Sinovial/patología

Asunto(s)

Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Morfinanos/uso terapéutico , Fitoterapia , Animales , Humanos , Interleucina-1beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

OBJECTIVE: To examine estrogen receptor (ER) in osteoblasts from adult human and to elucidate the mechanism of estrogen in modulating bone metabolism. METHODS: The cultured osteoblasts were harvested from bone chips by modified sequential digestive enzyme release and immunohistochemical assay of ER in osteoblasts were carried out in three groups of female adults: normal control (group 1), patients with moderate osteoporosis (group 2) and patients with serious osteoporosis (group 3). The percentages of ER-positive osteoblasts from the three groups were compared by t test. RESULTS: The brown marks that indicate ER were found in nuclei and plasma of the osteoblasts, and the percentages of ER-positive osteoblasts among three groups were significantly different. CONCLUSION: ERs exist in nuclei and plasma of the osteoblasts. Estrogen may modulate bone metabolism through binding ER in nuclei and plasma of the osteoblasts. The reduction of ER of osteoblasts may play an important role in the pathogenesis of postmenopausal osteoporosis.

Asunto(s)

Osteoblastos/metabolismo , Receptores de Estrógenos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Células Cultivadas , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Osteoblastos/citología , Osteoporosis/metabolismo , Osteoporosis/patología , Receptores de Estrógenos/análisis

RESUMEN

OBJECTIVE: To establish a stable, useful culture system for human osteoclasts and to investigate the effect of osteoblasts on the differentiation, proliferation and activation of osteoclasts so as to provide a base for the studies on prevention and treatment of osteolysis and osteoporosis. METHODS: In the presence of 1,25-(OH)2D3, monocytes abstracted from human bone marrow were cultured in three groups: co-culture of monocytes and osteoblasts, monocytes alone, monocytes with conditional media (CM) of osteoblasts. Differentiation process of the cultured cells was observed under biological microscope. HE staining and tartrate-resistant acid phosphatase (Trap) staining were employed to assay the cultured cells. The resorption pits on bone slices, on which cells were cultured, were observed under scanning electronic microscope (SEM). RESULTS: In the group of co-culture of monocytes and osteoblasts, monocytes gradually fused to form multinucleated cells (MNCs), and the MNCs were also indicated in HE staining and Trap staining. The SEM showed a number of resorption pits on bone slices. In the other two groups, Trap-positive MNCs were not obtained, and resorption pits were not observed on bone slices. CONCLUSION: In this culture, monocytes obtained from human marrow fused to form multinucleated cells (MNCs) that express the main characteristics of the osteoclast phenotype, such as Trap-positive and the ability to form resorption lacunae when cultured on bone slices. Cell-to-cell contact with osteoblasts was necessary for the differentiation, proliferation and activation of osteoclasts.

Asunto(s)

Técnicas de Cocultivo , Osteoclastos/citología , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Humanos , Monocitos/citología , Osteoblastos/citología