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BACKGROUND: Suction drainages are commonly used after total knee arthroplasty (TKA) procedures; however, their use is somewhat controversial. Recently, some reports have claimed that the administration of tranexamic acid (TXA) may prevent postoperative bleeding following TKAs. Although numerous studies have reported regarding different dosages, timings of administration, or drain clamping times for intravenous and intra-articular TXA injections (IA-TXAs), few have examined whether suction drainage is necessary when TXA is administered. In this study, we compared using suction drainage without TXA administration and IA-TXA without suction drainage and aimed to examine the need for suction drainage during IA-TXA. METHODS: This retrospective study was conducted on 217 patients who had received TKA for osteoarthritis; 104 were placed on suction drainage after TKA without TXA (Group A), whereas the remaining 113 received IA-TXA immediately after surgery without suction drainage (Group B). Our clinical evaluation included assessments of the need for transfusion, presence of postoperative complications, incidence of deep vein thrombosis (DVT), and changes in hemoglobin (Hb), hematocrit (Hct), and D-dimer levels. RESULTS: No significant differences were observed in terms of postoperative complications and preoperative Hb, Hct, or D-dimer levels between the two groups. Although the prevalence of DVT was significantly higher in Group B (p < 0.05), all cases were asymptomatic. Hb and Hct levels were significantly lower in Group A than in Group B at 1, 3, 7, and 14 days postoperatively (p < 0.05), although none of the cases required blood transfusions. D-dimer levels were significantly higher in Group A than in Group B at 1 and 3 days postoperatively (p < 0.05). CONCLUSION: Suction drainage might not be necessary when IA-TXA is administered after TKA procedures.
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Antifibrinolíticos , Artroplastia do Joelho , Hemorragia Pós-Operatória , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/efeitos adversos , Estudos Retrospectivos , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Feminino , Masculino , Idoso , Sucção , Injeções Intra-Articulares , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/efeitos adversos , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/prevenção & controle , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/epidemiologia , Idoso de 80 Anos ou mais , Osteoartrite do Joelho/cirurgia , Trombose Venosa/prevenção & controle , Trombose Venosa/etiologia , Trombose Venosa/epidemiologia , Resultado do TratamentoRESUMO
Diabetes mellitus (DM) has been suggested as a potential risk factor for knee osteoarthritis (KOA), and its underlying mechanisms remain unclear. The infrapatellar fat pad (IPFP) contributes to OA through inflammatory mediator secretion. Mast cells' (MCs) role in diabetic IPFP pathology is unclear. In 156 KOA patients, hemoglobin A1c (HbA1c) was stratified (HbA1c ≥ 6.5, n = 28; HbA1c < 6.5, n = 128). MC markers (TPSB2, CPA3) in IPFP were studied. Propensity-matched cohorts (n = 27 each) addressed demographic differences. MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF) were isolated, comparing MC markers and genes elevated in diabetic skin-derived MC (PAXIP1, ARG1, HAS1, IL3RA). TPSB2 and CPA3 expression were significantly higher in HbA1c ≥ 6.5 vs. <6.5, both before and after matching. MC-RF showed higher TPSB2 and CPA3 expression than MC-PF in both groups. In the HbA1c ≥ 6.5 group, PAXIP1 and ARG1 expression were significantly higher in the MC-RF than MC-PF. However, no statistical difference in the evaluated genes was detected between the High and Normal groups in the MC-RF. Elevated TPSB2 and CPA3 levels in the IPFP of high HbA1c patients likely reflect higher numbers of MCs in the IPFP, though no difference was found in MC-specific markers on a cell-to-cell basis, as shown in the MC-RF comparison. These findings deepen our understanding of the intricate interplay between diabetes and KOA, guiding targeted therapeutic interventions.
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Diabetes Mellitus , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/genética , Hemoglobinas Glicadas , Mastócitos , Fenótipo , Serina Proteases , Diabetes Mellitus/genéticaRESUMO
(1) Introduction: Despite documented clinical and pain discrepancies between male and female osteoarthritis (OA) patients, the underlying mechanisms remain unclear. Synovial myofibroblasts, implicated in synovial fibrosis and OA-related pain, offer a potential explanation for these sex differences. Additionally, interleukin-24 (IL24), known for its role in autoimmune disorders and potential myofibroblast production, adds complexity to understanding sex-specific variations in OA. We investigate its role in OA and its contribution to observed sex differences. (2) Methods: To assess gender-specific variations, we analyzed myofibroblast marker expression and IL24 levels in synovial tissue samples from propensity-matched male and female OA patients (each n = 34). Gene expression was quantified using quantitative polymerase chain reaction (qPCR). The association between IL24 expression levels and pain severity, measured by a visual analog scale (VAS), was examined to understand the link between IL24 and OA pain. Synovial fibroblast subsets, including CD45-CD31-CD39- (fibroblast) and CD45-CD31-CD39+ (myofibroblast), were magnetically isolated from female patients (n = 5), and IL24 expression was compared between these subsets. (3) Results: Females exhibited significantly higher expression of myofibroblast markers (MYH11, ET1, ENTPD2) and IL24 compared to males. IL24 expression positively correlated with pain severity in females, while no correlation was observed in males. Further exploration revealed that the myofibroblast fraction highly expressed IL24 compared to the fibroblast fraction in both male and female samples. There was no difference in the myofibroblast fraction between males and females. (4) Conclusions: Our study highlights the gender-specific role of myofibroblasts and IL24 in OA pathogenesis. Elevated IL24 levels in females, correlating with pain severity, suggest its involvement in OA pain experiences. The potential therapeutic implications of IL24, demonstrated in autoimmune disorders, open avenues for targeted interventions. Notwithstanding the limitations of the study, our findings contribute to understanding OA's multifaceted nature and advocate for future research exploring mechanistic underpinnings and clinical applications of IL24 in synovial myofibroblasts. Additionally, future research directions should focus on elucidating the precise mechanisms by which IL24 contributes to OA pathology and exploring its potential as a therapeutic target for personalized medicine approaches.
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Interleucinas , Miofibroblastos , Osteoartrite , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Interleucinas/genética , Interleucinas/imunologia , Miofibroblastos/imunologia , Osteoartrite/genética , Osteoartrite/imunologia , Dor/genética , Dor/imunologia , Pontuação de Propensão , Fatores Sexuais , Membrana Sinovial/inervaçãoRESUMO
BACKGROUND: In primary total knee arthroplasty (TKA), tibial bone defects ≥ 10 mm in depth often become uncontained defects, a condition most surgeons find challenging to treat. Although the allogenous bone graft is a useful method, complications such as infection and nonunion are likely to occur. There are several reports on the use of allogenous bone graft in revision TKA; however, few studies have investigated its use in primary TKA. We performed primary TKA using the allogenous bone graft as a structural bone graft to treat uncontained defects ≥ 10 mm in depth. This study aimed to assess the clinical and radiographical results after primary TKA with allogenous structural bone graft (ASBG). METHODS: Seventeen patients (mean age, 69.2 years) with a follow-up period of at least 7 years, were retrospectively reviewed. All cases had been treated for medial bone defects using the ipsilateral medial tibial allogenous bone. Clinical evaluation included the assessment of the knee and function scores and knee angle, and the hip-knee-ankle (HKA) angle, bone union, and radiolucent line (RL) were assessed radiologically. RESULTS: The mean depth of the medial tibial defects after tibia cutting was 16.8 mm. Nonunion occurred in one case, and RL occurred in another. We observed a significant difference when the preoperative knee score and HKA angle of patients was compared with that at 1 year postoperatively and the final evaluation. No major complications were observed. CONCLUSION: The ASBG technique produced favorable surgical outcomes and may be an acceptable procedure for managing uncontained tibial bone defects ≥ 10 mm in depth in primary TKA.
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Artroplastia do Joelho , Prótese do Joelho , Idoso , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Transplante Ósseo/métodos , Humanos , Estudos Retrospectivos , Tíbia/diagnóstico por imagem , Tíbia/cirurgiaRESUMO
Obesity is a risk factor for knee osteoarthritis (KOA). Neuromedin U (NMU) and NMU receptors (NMUR1 and NMUR2) are associated with obesity-related disorders and found in mast cells (MCs), which are elevated in osteoarthritis. However, NMU/NMUR expression was not examined in the synovial membrane (SM) or synovial MCs of obese osteoarthritis patients. We compared expression of NMU, NMUR1, NMUR2, and the mast cell (MC) marker, CPA3, in the SM of KOA patients categorized as normal weight (NW; BMI < 25 kg/m2, n = 79), overweight (OW; BMI ≥ 25 and <30 kg/m2, n = 87), and obese (OB; ≥30 kg/m2, n = 40). To study NMU/NMUR expression in MCs, we compared the MC-rich fraction (MC-RF), CD88(+) MC-RF, and CD88(−) MC-RF, extracted using magnetic isolation, with the MC-poor fraction (MC-PF). While NMU and NMUR2 expression were comparable, NMUR1 was significantly elevated in OW and OB compared to NW. Moreover, CPA3 levels were significantly greater in OB than NW. NMUR1 and CPA3 expression were significantly higher in both the CD88(+) and CD88(−) MC-RF than MC-PF. Therefore, NMUR1 expression was elevated in the SM of OB KOA patients, and its expression was found in MCs. Further investigation to analyze the NMU/NMUR1 pathway in MC may provide a link between obesity and KOA pathology.
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Mastócitos , Osteoartrite , Humanos , Obesidade/complicações , Receptores de Neurotransmissores , Membrana SinovialRESUMO
Several studies have implicated ß2-microglobulin (B2M) in osteoarthritis (OA) pathology. Of the main constituents of synovial tissue, synovial fibroblasts and macrophages, the latter play a pivotal role in inflammation. Although several studies have investigated the effects of B2M on synovial fibroblasts, few have examined the impact on synovial macrophages. Here, we investigated the effect of B2M on the expression profiles of inflammatory cytokines and matrix metalloproteases (MMPs) in synovial macrophages. Synovial macrophages were isolated from the osteoarthritic synovium using an anti-CD14 anti- body and magnetic isolation system. Synovial macrophages were stimulated with B2M for 6 and 24 h. Following stimulation, cell surface marker (CD80, CD163, CD206), cytokine [interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α)] and matrix metalloprotease (MMP; MMP-9 and MMP-13) genes were evaluated by real-time PCR. Additionally, cytokine concentrations in cell culture supernatant were determined using enzyme-linked immunosorbent assay (ELISA). B2M significantly increased CD80 and decreased CD163 expression. In addition, B2M stimulation increased inflammatory cytokines at both the mRNA and protein levels. While B2M likewise elevated MMP-13 levels, there was no difference in MMP-9 expression between vehicle and B2M-treated cells. B2M increased M1 macrophage marker, inflammatory cytokine, and MMP-13 expression in synovial macrophages. B2M-related activation of synovial macrophages may thus be associated with OA pathology.
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Rheumatoid arthritis (RA), a systemic autoimmune disease, is known to cause chronic inflammation in synovial joints. A number of inflammatory conditions are associated with stimulation of Clec4e, a macrophage-inducible C-type lectin (MINCLE) and transmembrane pattern recognition receptor that functions in innate immunity. We previously reported MINCLE expression in synovial macrophages isolated from the synovium of osteoarthritis (OA) patients. However, MINCLE expression has not been examined in RA synovial tissue. To examine MINCLE expression in RA patients, synovial tissue specimens were obtained from patients with RA and OA during joint replacement surgery (n = 20 each). Total RNA was extracted from synovial tissue and used to compare MINCLE expression in OA and RA (n = 15 each). We also extracted fresh CD14+ (macrophage-rich) and CD14- cell fractions from synovial tissue and compared MINCLE expression between OA and RA patients (n = 5 each). MINCLE levels in synovial tissue were significantly elevated in RA patients compared to OA patients. MINCLE expression was significantly elevated in the CD14+ fraction compared to the CD14- fraction in both OA and RA patients. Further, while there were no differences in the CD14+ fraction between RA and OA, MINCLE expression in the CD14- fraction was elevated in RA compared to OA. Our findings indicate that MINCLE expression is elevated in the synovium of RA patients and that MINCLE expression in non-macrophage cell fractions may be a key feature of RA.
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INTRODUCTION: Obesity appears to be a powerful risk factor for the development of knee osteoarthritis (KOA), but the mechanisms of this are not fully understood. CD5L is expressed in tissue macrophages and is increased in obese mice. We hypothesized that CD5L expression is increased in the synovial membrane (SM) of obese KOA patients. Here, we investigated CD5L expression in the SM of these patients. MATERIAL AND METHODS: Ninety KOA patients (26 males, 64 females) were allocated to one of three groups based on body mass index (BMI): normal weight (NW, < 25 kg/m2), overweight (OW, 25-29.99 kg/m2) and obese (OB, ≥ 30 kg/m2), according to the World Health Organization BMI classification (each n = 30). Expression of CD5L in SM among the groups was compared using real-time polymerase chain reaction. To investigate CD5L-expressing cells in SM, CD14+ (macrophage fraction) and CD14- (fibroblast fraction) cells were separated from the SM. RESULTS: CD5L expression was significantly higher in the OB group than in the NW and OW groups (p < 0.001). CD5L expression was observed in the CD14+ fraction but not in the CD14- fraction. CONCLUSIONS: CD5L is highly expressed in the SM of KOA patients with obesity. Further investigation is required to identify the role of CD5L in the relationship between KOA pathology and obesity.
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Recent evidence suggests that synovial macrophage activation may be involved in cartilage destruction and pain in osteoarthritis (OA). The macrophage-inducible C-type lectin (Mincle) Clec4e is expressed in macrophages and is regulated in inflammatory conditions. Given that the regulation of Mincle in synovial macrophages has not been elucidated, we investigated the expression and regulation of Mincle in human synovial tissue (ST) harvested from patients with radiographic knee OA during total knee arthroplasty. Immunohistochemical and flow cytometric analyses were used to identify cells with Mincle expression in resected tissues. CD14-positive (CD14+; macrophage-rich cell fraction) and CD14-negative (CD14-; fibroblast-rich cell fraction) cells were extracted from the ST and used to assess MINCLE mRNA expression levels. To determine the role of tumor necrosis factor alpha (TNF-α) in the regulation of MINCLE expression, TNF-α was used to stimulate cultured CD14+ cells. Immunohistochemical staining revealed Mincle-positive cells in the synovial lining layer. Flow cytometric analysis showed that CD45+CD14+ cells were Mincle positive while CD45-/CD14- cells were Mincle negative. MINCLE expression was significantly higher in CD14+ cells than in CD14- cells. Stimulation of cultured CD14+ macrophages with TNF-α significantly increased MINCLE mRNA expression, while stimulation with TNF-α neutralizing antibody significantly decreased expression. That Mincle expression was observed in synovial macrophages and its expression was induced by TNF-α suggests that Mincle might have a key role in synovial inflammation in the osteoarthritic synovium.
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BACKGROUND: Nerve growth factor (NGF) contributes to pain in knee osteoarthritis (KOA) patients. Transforming growth factor-beta (TGF-ß) stimulates NGF expression in chondrocytes from KOA patients. However, the correlation between synovial TGF-ß and NGF levels has not been sufficiently studied in human KOA patients. Further, the mechanism governing NGF regulation by TGF-ß in synovial cells is unclear. METHODS: During total knee arthroplasty, we extracted the synovial tissue (SYT) of 107 subjects with unilateral Kellgren/Lawrence grade 3-4 KOA confirmed by radiography. We examined the distribution of TGF-ß and NGF using immunohistochemistry, and analyzed the relationship between NGF and TGFB mRNA levels. Cultured synovial cells extracted from SYT were exposed to culture medium (control), human recombinant TGF-ß (rhTGF-ß), rhTGF-ß + ALK5 inhibitor SB505124, rhTGF-ß + transforming growth factor activating kinase 1 (TAK1) inhibitor (5Z)-7-oxozeaenol, or rhTGF-ß + p38 inhibitor SB203580 for 30 min, 6 h and 24 h. NGF mRNA expressed by the cultured cells and NGF protein levels in the cell supernatant were detected by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Phosphorylation of p38 was evaluated by western blotting. RESULTS: NGF mRNA levels were positively correlated with those of TGFB. Cells expressing TGF-ß and NGF protein were observed in the lining layer of SYT. TGF-ß stimulated increased NGF mRNA expression and NGF protein production. The ALK5 inhibitor completely suppressed the TGF-ß-mediated increase in NGF expression and NGF production in synovial cells. ALK5, TAK1 and p38 inhibitors inhibited the TGF-ß-induced phosphorylation of p38, and TAK1 and p38 inhibitors partially inhibited the TGF-ß-mediated increase in NGF expression and NGF production in synovial cells. CONCLUSION: TGF-ß regulates NGF production via the TGF-ß/ALK5 signaling pathway in osteoarthritic synovium. This effect may partially occur through inhibition of the TAK1/p38 pathway in the SYT of KOA patients.
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Artralgia/patologia , Fator de Crescimento Neural/metabolismo , Osteoartrite do Joelho/complicações , Membrana Sinovial/patologia , Fator de Crescimento Transformador beta1/metabolismo , Idoso , Artralgia/etiologia , Células Cultivadas , Feminino , Humanos , Masculino , Osteoartrite do Joelho/patologia , Cultura Primária de Células , Membrana Sinovial/citologia , Sinoviócitos/metabolismoRESUMO
BACKGROUND: The infrapatellar fat pad (IFP) is implicated in knee osteoarthritis (KOA). Calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide expressed in joint tissues and synovial tissues (ST), was recently found to be associated with KOA progression and pain. CGRP is expressed in the IFPs of human KOA patients; however, its regulation has not been elucidated. METHODS: IFPs and STs were harvested from 138 KOA patients during total knee replacement (TKR) and analyzed for CGRP, cycloxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) expression using real-time polymerase chain reaction (PCR). To investigate CGRP regulation by prostaglandin E2 (PGE2), adipocytes (Ad) and the stromal vascular fraction (SVF) were harvested from IFPs using collagenase. Synovial cells (SYC) were also harvested from ST and stimulated with vehicle (serum-free culture medium), PGE2, or CGRP. RESULTS: CGRP, COX-2, and mPGES-1 expression levels were significantly higher in IFPs than STs. PGE2 stimulation increased CGRP expression in Ad, the SVF, and SYC; however, CGRP expression was significantly higher in PGE2-stimulated SVF than PGE2-stimulated SYC. CGRP stimulation had no effect on COX-2 or mPGES-1 expression. CONCLUSIONS: CGRP expression in the IFP of KOA patients is regulated by the COX-2/mPGES-1/PGE2 pathway.
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Tecido Adiposo/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/genética , Osteoartrite do Joelho/genética , Tecido Adiposo/patologia , Idoso , Idoso de 80 Anos ou mais , Ciclo-Oxigenase 2/genética , Dinoprostona/genética , Regulação da Expressão Gênica , Humanos , Osteoartrite do Joelho/patologia , Prostaglandina-E Sintases/genética , Transdução de Sinais/genéticaRESUMO
BACKGROUND: While epidemiological studies have reported a potential role for hypercholesterolemia (HCE) in osteoarthritis (OA), the association between HCE and OA has yet to be clarified. Adipose tissue is a primary locus for cholesterol metabolism and the presence of HCE reportedly causes adipose dysfunction. The knee joint contains adipose tissue in the form of the infrapatellar fat pad (IPFP), which has been shown to contribute to the pathophysiology of OA in the knee via the secretion of inflammatory mediators. However, the effect of HCE on the expression of inflammatory mediators in the IPFP has not been elucidated. METHODS: IPFP and synovial tissues (ST) were extracted from 145 subjects with OA, diagnosed by radiography, during total knee arthroplasty. OA patients were divided into three groups according to their total cholesterol levels (Desirable, Borderline high and High) based on the National Cholesterol Education Program Adult Treatment Panel III (NCEPATP III). We examined the expression of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES1), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 using real-time polymerase chain reaction and compared results among the Desirable, Borderline high and High groups. RESULTS: The mRNA expression levels of TNF-α, IL-1ß, and IL-6 in ST and the IPFP were not significantly different among the three groups. COX-2 mRNA expression in ST and IPFP was likewise not different among the three groups. While the mRNA expression level of mPGES1 in ST was also not significantly different, that of mPGES1 in the IPFP was significantly lower in the High group than in the Desirable and Borderline high groups. CONCLUSION: mRNA levels of mPGES-1 are reduced in the IPFP of knee OA patients with HCE. Additional studies are need to clarify the effect of mPGES-1 down-regulation in OA pathology.
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Tecido Adiposo/metabolismo , Colesterol/metabolismo , Hipercolesterolemia/genética , Osteoartrite do Joelho/genética , Prostaglandina-E Sintases/genética , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Hipercolesterolemia/cirurgia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Cápsula Articular/metabolismo , Masculino , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Patela/metabolismo , Prostaglandina-E Sintases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Research suggests that vascular endothelial growth factor (VEGF) levels in the synovial fluid of knee osteoarthritis (KOA) patients are positively correlated with KOA severity. The relationship between synovial VEGF levels and pain in human KOA patients is not fully understood, and the role of VEGF in the pain pathway remains unclear. METHODS: We harvested synovial membrane (SM) from 102 patients with radiographic evidence of KOA (unilateral Kellgren/Lawrence [K/L] grade 2-4) during total knee arthroplasty. Patients scored their pain on a 0 to 10 cm visual analog scale (VAS). VEGF levels in the SM of KOA patients with strong/severe (VAS ≥ 6) and mild/moderate pain (VAS < 6) were compared. Correlations between VAS and VEGF mRNA expression were investigated. To investigate a possible mechanism for VEGF-induced pain, the distribution of VEGF and the neuropeptide apelin was determined by immunohistochemical analyses. To investigate the role of VEGF in regulating apelin expression, SM cells were exposed to VEGF. RESULTS: VEGF expression in the VAS ≥ 6 group was significantly greater than expression in the VAS < 6 group. Expression levels of VEGF were also positively correlated with VAS. VEGF-positive cells were identified in the lining of the SM. Expression of apelin mRNA and protein were significantly elevated in SM cells treated with exogenous VEGF compared to those treated with vehicle. CONCLUSION: Synovial VEGF may be involved in pain pathways in KOA and its action may be mediated by apelin.
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Osteoartrite do Joelho/metabolismo , Dor/metabolismo , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/farmacologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Dor/patologia , Medição da Dor/métodos , Membrana Sinovial/patologia , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: Recent studies have suggested that the tumor necrosis factor-α (TNF-α) pathway is a potential target for the management of osteoarthritis (OA). Transforming growth factor (TGF)-ß-activated kinase 1 (TAK1) is essential in several cytokine-mediated cascades, including the TNF-α, interleukin-1 (IL-1), and TGF-ß pathways. The role of TAK1 in synovial tissue in OA is not fully understood. Using synovial cells harvested from OA patients during surgery, we investigated whether TAK1 inhibition suppresses production of TNF-α-induced extracellular matrix degrading enzymes and expression of pain-related molecules. METHODS: Synovial tissues were harvested from ten subjects with radiographic evidence of osteoarthritis (OA) during total knee arthroplasty. Synovial cells were cultured and stimulated with control (culture media), 10 ng/mL human recombinant TNF-α, or 10 ng/mL TNF-α and 10 µM of the TAK1 inhibitor (5Z)-7-oxozeaenol for 24 h. Real-time polymerase chain reaction (PCR) analysis was used to monitor expression of mRNA of the extracellular matrix degrading enzymes matrix metalloproteinase-3 (MMP-3) and a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 4 (ADAMTS-4); and of the pain-related molecules cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), and nerve growth factor (NGF). MMP-3 and NGF protein concentrations in cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). COX-2, mPGES-1 and ADAMTS-4 protein expression was also evaluated by western blotting. RESULTS: TNF-α stimulated increases in ADAMTS-4 and MMP3 mRNA (2.0-fold and 1.6-fold, respectively, p < 0.05) and protein expression (21.5-fold and 2.0-fold, respectively). Treatment with the TAK1 inihibitor (5Z)-7-oxozeaenol reduced ADAMTS-4 and MMP3 mRNA (0.5-fold and 0.6-fold, respectively) and protein expression (1.4-fold and 0.5-fold, respectively) in OA synovial cells. COX-2, mPGES-1 and NGF mRNA (11.2-fold, 3.1-fold and 2.7-fold, respectively) and protein expression (3.0-fold, 2.7-fold and 2.2-fold, respectively) were increased by TNF-α. (5Z)-7-oxozeaenol treatment reduced mPGES1 and NGF mRNA (1.5-fold and 0.8-fold, respectively) and protein (1.5-fold and 0.5-fold, respectively). CONCLUSION: TAK1 plays an important role in the regulation of TNF-α induced extracellular matrix degrading enzymes and pain-related molecule expression. TAK1 may be a potential target for therapeutic strategies aimed at preventing osteoarthritis progression and pain.
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Artralgia/metabolismo , Matriz Extracelular/enzimologia , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/fisiologia , Líquido Sinovial/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Idoso , Idoso de 80 Anos ou mais , Artralgia/cirurgia , Artroplastia do Joelho/tendências , Células Cultivadas , Matriz Extracelular/efeitos dos fármacos , Feminino , Expressão Gênica , Humanos , Lactonas/farmacologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/cirurgia , Resorcinóis/farmacologia , Líquido Sinovial/efeitos dos fármacosRESUMO
BACKGROUND AND PURPOSE: Sarcopenia is known to be associated with poor outcomes after arthroplasty; however, no study has reported the relationship between sarcopenia and postoperative walking independence. This study aimed to determine the impact of sarcopenia risk screening using the SARC-CalF questionnaire and calf circumference on the time to walk independently after total hip or knee arthroplasty in older patients. METHODS: We included 599 nonobese patients aged 65 years and older who underwent unilateral and primary total hip or knee arthroplasty. Preoperative sarcopenia risk was assessed using the SARC-CalF or calf circumference. The outcome of this study was the time to independent walking after surgery; it was calculated as the number of days from the date of surgery to the date when the patient was able to walk independently. The association between preoperative sarcopenia risk and time to independent walking after surgery was analyzed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Among the 599 patients undergoing total joint arthroplasty, 175 (29.2%) were determined to be at risk of sarcopenia using SARC-CalF and 193 (32.2%) using calf circumference. The Kaplan-Meier curve showed that sarcopenia risk assessed by SARC-CalF or calf circumference was associated with a prolonged time to independent walking in patients undergoing hip arthroplasty (log-rank test, P < .001 and P < .001, respectively). In patients undergoing hip arthroplasty, the Cox proportional hazards model showed that SARC-CalF score of 11 points and greater or a calf circumference less than the cutoff was a risk factor for delayed time to independent walking (hazard ratios: 0.55 and 0.57, P < .001 and P = .001, respectively). There was no association between preoperative sarcopenia risk and postoperative time to independent walking in patients who underwent knee arthroplasty. CONCLUSIONS: Sarcopenia screening tools, such as SARC-CalF or calf circumference, should be useful for planning postoperative rehabilitation in older adults scheduled for hip arthroplasty. However, the accuracy of SARC-CalF or calf circumference measurement in patients scheduled for knee arthroplasty may be low.
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Artroplastia do Joelho , Sarcopenia , Humanos , Idoso , Sarcopenia/epidemiologia , Sarcopenia/diagnóstico , Perna (Membro) , Caminhada , Inquéritos e Questionários , Avaliação Geriátrica , Programas de RastreamentoRESUMO
BACKGROUND: This is the first study to objectively assess the athletic ability of school-age congenital clubfoot patients. METHODS: Forty-six feet of 30 patients (18 boys, 12 girls) were evaluated in this study. Nine patients were treated conservatively, 8 patients underwent percutaneous tenotomy of the Achilles tendon, and 13 patients were treated with extensive soft-tissue release. The mean age at the investigation was 9.2±1.9 years, and the mean follow-up period was 8.3±2.9 years. Athletic ability was evaluated by calculating Z-scores for the patients' scores in 5 physical fitness tests routinely performed nationwide at elementary schools: 50-meter run; standing long jump; repetition side steps; 20-meter shuttle run; and sit-ups. The Z-scores were calculated based on data published as the nationwide standards. RESULTS: Of the 148 scores recorded for the 5 tests for the 30 clubfoot patients, 143 scores (96.6%) were higher than the -2 SD value. The mean Z-scores were as follows: -0.32 for 50-meter run; -0.16 for standing long jump; -0.24 for 20-meter shuttle run; 0.22 for repetition side steps; and 0.06 for sit-ups. None of the events showed any significant differences among the three treatment groups. CONCLUSIONS: Congenital clubfoot with satisfactory treatment did not significantly impair the athletic performance. LEVEL OF EVIDENCE: Prognostic level III.
Assuntos
Pé Torto Equinovaro/terapia , Aptidão Física , Esportes , Criança , Feminino , Humanos , Masculino , Indução de RemissãoRESUMO
There are various techniques used for tendon lengthening, of which Z-lengthening and sliding-lengthening are the most frequently performed. In patients with cerebral palsy, tendon lengthening may often be necessary at multiple sites. However, they can cause various complications, such as inaccurate extension, overextension, and a lack of tendon continuity. We modified the sliding-lengthening technique with a locking mechanism to address these issues. This technical note aims to describe the surgical technique and pitfalls associated with the modified sliding-lengthening approach and suture locking mechanism. The tendon was exposed and stabilized using sterilized spitz tubes and was then threaded so that each loop length was equivalent to the amount of tendon extension. Symmetrical hemisection of both ends of the tendon was performed, and the tendon was carefully extended to create a tense loop. The modified sliding-lengthening technique with the locking suture mechanism may be an advantageous method that accurately addresses extension volume, prevents hyperextension, and maintains tendon continuity, even when smaller incisions are used.
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Recent studies utilizing single-cell analysis have unveiled the presence of various fibroblast (Fb) subsets within the synovium under inflammatory conditions in osteoarthritis (OA), distinguishing them from those in rheumatoid arthritis (RA). Moreover, it has been reported that pain in knee OA patients is linked to specific fibroblast subsets. Single-cell expression profiling methods offer an incredibly detailed view of the molecular states of individual cells. However, one limitation of these methods is that they require the destruction of cells during the analysis process, rendering it impossible to directly assess cell function. In our study, we employ flow cytometric analysis, utilizing cell surface markers CD39 and CD55, in an attempt to isolate fibroblast subsets and investigate their relationship with OA pathology. Synovial tissues were obtained from 25 knee OA (KOA) patients. Of these, six samples were analyzed by RNA-seq (n = 3) and LC/MS analysis (n = 3). All 25 samples were analyzed to estimate the proportion of Fb (CD45-CD31-CD90+) subset by flow cytometry. The proportion of Fb subsets (CD39+CD55- and CD39-CD55+) and their association with osteoarthritis pathology were evaluated. CD39+CD55- Fb highly expressed myogenic markers such as CNN1, IGFBP7, MYH11, and TPM1 compared to CD39-CD55+ Fb. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of upregulated differentially expressed genes (DEGs) in CD39+CD55- Fb identified the Apelin pathway and cGMP-PKC-signaling pathway as possibly contributing to pain. LC/MS analysis indicated that proteins encoded by myogenic marker genes, including CNN1, IGFBP7, and MYH11, were also significantly higher than in CD39-CD55+ Fb. CD39-CD55+ Fb highly expressed PRG4 genes and proteins. Upregulated DEGs were enriched for pathways associated with proinflammatory states ('RA', 'TNF signaling pathway', 'IL-17 signaling pathway'). The proportion of CD39+CD55- Fb in synovium significantly correlated with both resting and active pain levels in knee OA (KOA) patients (resting pain, ρ = 0.513, p = 0.009; active pain, ρ = 0.483, p = 0.015). There was no correlation between joint space width (JSW) and the proportion of CD39+CD55- Fb. In contrast, there was no correlation between the proportion of CD39-CD55+ Fb and resting pain, active pain, or JSW. In conclusion, CD39+CD55- cells exhibit a myofibroblast phenotype, and its proportion is associated with KOA pain. Our study sheds light on the potential significance of CD39+CD55- synovial fibroblasts in osteoarthritis, their myofibroblast-like phenotype, and their association with joint pain. These findings provide a foundation for further research into the mechanisms underlying fibrosis, the impact of altered gene expression on osteoarthritic joints, and potential therapeutic strategies.
RESUMO
ABSTRACT: Whether femoral varus derotational osteotomy (VDRO) alone or a combination of femoral and pelvic osteotomies should be performed for hip dislocation in nonambulatory children with cerebral palsy (CP) remains controversial. Few studies have reported radiographical results after the surgical treatment in nonambulatory children with CP. This study aimed to assess the results and determine predictors indicating progressive hip subluxation and redislocation after VDRO without pelvic osteotomy. We retrospectively analyzed 22 hips in 15 nonambulatory children with CP. All patients underwent VDRO without pelvic osteotomy and were followed up for at least 5âyears. The mean follow-up period was 7.3â±â1.9âyears. In radiological assessments, we investigated migration percentage (MP), center-edge angle, neck-shaft angle, teardrop distance, break in Shenton's line (SL), sharp's angle, acetabular ridge angle (ARA), and the change ratio of MP (Change MP). We classified patients with an MP of <40% at final follow-up in the Good group and those with an MP of ≥40% in the Poor group. The Good group included 10 children (14 hips), and the Poor group included 8 children (8 hips). No preoperative differences were found in the means of all the radiographical parameters. However, MP was significantly different between the groups from 1âyear postoperatively. ARA showed improvement 5âyears after surgery in the Good group. Change MP in the Good group was maintained from immediately after surgery to the final follow-up. Multivariate logistic regression analyses revealed that preoperative break in SL and Change MP immediately after surgery were parameters to predict MP at the final follow-up. In the receiver operating characteristic analysis, the cut-off values were estimated to be 19.2âmm for preoperative SL and 79.0% for Change MP immediately after surgery. Within 7.3âyears of follow-up, 63.6% of the patients who underwent VDRO without pelvic osteotomy had good results. Preoperative SL and postoperative Change MP can be considered as predictors of postoperative subluxation and/or dislocation.