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Clinics (Sao Paulo, Brazil) May 2024This study was directed towards exploring the impacts of lncRNA HOXA11-AS-mediated microRNA (miR)-506-3p on chondrocytes proliferation and apoptosis in osteoarthritis...
OBJECTIVES
This study was directed towards exploring the impacts of lncRNA HOXA11-AS-mediated microRNA (miR)-506-3p on chondrocytes proliferation and apoptosis in osteoarthritis (OA).
METHODS
The articular cartilages were provided by OA patients who received total knee arthroplasty, and Human Chondrocyte (HC)-OA (HCOA) was also attained. The miR-506-3p and HOXA11-AS expressions in articular cartilages from OA patients and HCOA cells were analyzed via qPCR. After gain- and loss-of-function assays in HCOA cells, MTT assay and flow cytometry (FC) were used for assessing cell viability and apoptosis, accordingly. The levels of PIK3CA, AKT, and mTOR as well as AKT and mTOR phosphorylation levels assessed using western blotting (WB). The targeting correlation of HOXA11-AS and miR-506-3p as well as miR-506-3p and PIK3CA was assessed through Dual-Luciferase Reporter gene Assay (DLRA).
RESULT
The articular cartilages from OA patients and Human Chondrocyte (HC)-OA (HCOA) cells showed increased HOXA11-AS and decreased miR-506-3p. Mechanistically, HOXA11-AS was capable of binding to miR-506-3p to increase PIK3CA, the target gene of miR-506-3p. miR-506-3p suppression facilitated HCOA cell proliferation and reduced their apoptosis, which was nullified by further silencing HOXA11-AS or silencing PIK3CA. The down-regulation of HOXA11-AS disrupted the PI3K/AKT/mTOR pathway, which was counteracted by further miR-506-3p inhibition.
CONCLUSION
The silencing of HOXA11-AS might block the PI3K/AKT/mTOR pathway through miR-506-3p up-regulation, thereby restricting HCOA cell proliferation and provoking apoptosis.
PubMed: 38815540
DOI: 10.1016/j.clinsp.2024.100393 -
Aging May 2024Osteoarthritis (OA), a degenerative joint disease, involves synovial inflammation, subchondral bone erosion, and cartilage degeneration. Ferroptosis, a regulated...
Osteoarthritis (OA), a degenerative joint disease, involves synovial inflammation, subchondral bone erosion, and cartilage degeneration. Ferroptosis, a regulated non-apoptotic programmed cell death, is associated with various diseases. This study investigates ferroptosis-related molecular subtypes in OA to comprehend underlying mechanisms. The Gene Expression Omnibus datasets GSE206848, GSE55457, GSE55235, GSE77298 and GSE82107 were used utilized. Unsupervised clustering identified the ferroptosis-related gene (FRG) subtypes, and their immune characteristics were assessed. FRG signatures were derived using LASSO and SVM-RFE algorithms, forming models to evaluate OA's ferroptosis-related immune features. Three FRG clusters were found to be immunologically heterogeneous, with cluster 1 displaying robust immune response. Models identified nine key signature genes via algorithms, demonstrating strong diagnostic and prognostic performance. Finally, qRT-PCR and Western blot validated these genes, offering consistent results. In addition, some of these genes may have implications as new therapeutic targets and can be used to guide clinical applications.
PubMed: 38814177
DOI: 10.18632/aging.205875 -
Arthroplasty Today Jun 2024The American Academy of Orthopaedic Surgeons (AAOS) Appropriate Use Criteria (AUC) for Surgical Management of Osteoarthritis of the Knee (2016) and Management of...
BACKGROUND
The American Academy of Orthopaedic Surgeons (AAOS) Appropriate Use Criteria (AUC) for Surgical Management of Osteoarthritis of the Knee (2016) and Management of Osteoarthritis of the Hip (2017) are intended to provide treatment recommendations for osteoarthritis (OA). This study examined the agreement of AUC appropriateness classifications with arthroplasty surgeon recommendations for total knee arthroplasty (TKA) and total hip arthroplasty (THA).
METHODS
The cohort included 558 OA patients (397 knee, 161 hip) referred to a specialty arthroplasty clinic. Surgeons completed the online AAOS AUC patient profiles to generate appropriateness ratings. Surgeons' recommendations for treatment were recorded. We performed univariate and bivariate analyses to evaluate relationships between AUC appropriateness and surgeon recommendations.
RESULTS
The knee OA AUC classified TKA as "appropriate" for 309 (77.8%) of the 397 knee OA patients. Surgeons recommended TKA for 123 (31.0%), resulting in 46.8% (n = 186) higher rate of "appropriate" classification by AUC than TKA recommendation by surgeons. Weighted Cohen's κ demonstrated slight agreement (κ = 0.06, 95% confidence interval: 0.04, 0.09) between AUC appropriateness and surgeon TKA recommendation. The hip OA AUC classified THA as "appropriate" for 98 (60.9%) of the 161 hip OA patients. Surgeons recommended THA for 76 (47.2%), resulting in 13.7% (n = 22) higher rate of "appropriate" classification by AUC than THA recommendation by surgeons. Weighted Cohen's κ demonstrated moderate agreement (κ = 0.47, 95% confidence interval: 0.37, 0.57) between the AUC appropriateness classification and the surgeon's THA recommendation.
CONCLUSIONS
AAOS AUC guidelines indicated surgical appropriateness significantly more than arthroplasty surgeons. AUC agreed slightly with surgeons for TKA and moderately for THA.
PubMed: 38812476
DOI: 10.1016/j.artd.2024.101386 -
Knee Surgery & Related Research May 2024Total knee arthroplasty (TKA) is the most effective treatment for end-stage adult knee osteoarthritis, but it has been reported that patient satisfaction may vary. A...
BACKGROUND
Total knee arthroplasty (TKA) is the most effective treatment for end-stage adult knee osteoarthritis, but it has been reported that patient satisfaction may vary. A malfunction of the patellofemoral joint may produce anterior knee pain (AKP) for several reasons. While some surgeons systematically resurface the patella despite the risk of potential complications such as fracture, loosening, or wear of the patella, others prefer to preserve it to reduce AKP and revision rates. This study aimed to evaluate whether patellar resurfacing had better clinical and functional outcomes, complications, and revision rates in patients undergoing simultaneous bilateral total knee arthroplasty.
METHODS
We conducted a prospective cohort study, including patients who underwent bilateral simultaneous TKA in which the patella was replaced in one knee and preserved in the other, with a minimum follow-up of 7 years. We assessed clinical and functional outcomes with the Knee Society Score (KSS) and Visual Analogue Scale (VAS); complications and revision rates were also registered.
RESULTS
The final series consisted of 43 patients with 86 knee arthroplasties. After a mean of 7.6 years of follow-up, no significant differences were found regarding KSS (clinical: 82.8 ± 7.4 versus 83.2 ± 3.4, p = 0.92; functional 89.1 ± 8.2: versus 90.4 ± 6.8; p = 0.99), VAS (2.0 ± 0.9 versus 1.8 ± 1.0; p = 0.84), complications (10.5% versus 8.1%; p = 0.57), or revision rates (2.3% versus 2.3%; p = 0.99) when comparing patellar resurfacing versus retention.
CONCLUSION
In the context of total knee arthroplasty, patellar replacement did not demonstrate statistically significant differences concerning patellar retention in clinical nor functional outcomes, AKP, complications, or revision rates after a minimum of 7 years of follow-up.
PubMed: 38812052
DOI: 10.1186/s43019-024-00225-6 -
Arthritis Research & Therapy May 2024Due to the unclear pathogenesis of osteoarthritis (OA), effective treatment for this ailment is presently unavailable. Accumulating evidence points to chondrocyte...
BACKGROUND
Due to the unclear pathogenesis of osteoarthritis (OA), effective treatment for this ailment is presently unavailable. Accumulating evidence points to chondrocyte senescence as a key driver in OA development. This study aims to identify OA-specific microRNAs (miRNAs) targeting chondrocyte senescence to alleviate OA progression.
METHODS
We screened and identified miRNAs differentially expressed in OA and normal cartilage, then confirmed the impact of miR-653-5p on chondrocyte functions and senescence phenotypes through in vitro experiments with overexpression/silencing. We identified interleukin 6 (IL-6) as the target gene of miR-653-5p and confirmed the regulatory influence of miR-653-5p on the IL-6/JAK/STAT3 signaling pathway through gain/loss-of-function studies. Finally, we assessed the therapeutic efficacy of miR-653-5p on OA using a mouse model with destabilization of the medial meniscus.
RESULTS
MiR-653-5p was significantly downregulated in cartilage tissues and chondrocytes from OA patients. Overexpression of miR-653-5p promoted chondrocyte matrix synthesis and proliferation while inhibiting chondrocyte senescence. Furthermore, bioinformatics target prediction and the luciferase reporter assays identified IL-6 as a target of miR-653-5p. Western blot assays demonstrated that miR-653-5p overexpression inhibited the protein expression of IL-6, the phosphorylation of JAK1 and STAT3, and the expression of chondrocyte senescence phenotypes by regulating the IL-6/JAK/STAT3 signaling pathway. More importantly, the cartilage destruction was significantly alleviated and chondrocyte senescence phenotypes were remarkably decreased in the OA mouse model treated by agomiR-653-5p compared to the control mice.
CONCLUSIONS
MiR-653-5p showed a significant decrease in cartilage tissues of individuals with OA, leading to an upregulation of chondrocyte senescence phenotypes in the articular cartilage. AgomiR-653-5p emerges as a potential treatment approach for OA. These findings provide further insight into the role of miR-653-5p in chondrocyte senescence and the pathogenesis of OA.
Topics: MicroRNAs; Chondrocytes; Animals; Humans; Cellular Senescence; Osteoarthritis; Mice; Male; Interleukin-6; Mice, Inbred C57BL; STAT3 Transcription Factor; Cells, Cultured; Middle Aged; Female; Signal Transduction; Cartilage, Articular
PubMed: 38812033
DOI: 10.1186/s13075-024-03334-5 -
Journal of Orthopaedic Surgery and... May 2024To investigate the effect and underlying mechanism of umbilical cord blood-mononuclear cells (UCB-MNCs) in treating knee osteoarthritis (KOA) in rabbits.
BACKGROUND
To investigate the effect and underlying mechanism of umbilical cord blood-mononuclear cells (UCB-MNCs) in treating knee osteoarthritis (KOA) in rabbits.
METHODS
A rabbit KOA model was prepared by anterior cruciate ligament transection (ACLT). Fifty New Zealand white rabbits were randomly divided into the control group, model group, sodium hyaluronate (SH) group, platelet-rich plasma (PRP) group and UCB-MNC group. Knee injections were performed once a week for five consecutive weeks. The gross view of the knee joint, morphology of knee cartilage and structural changes in the knee joint were observed on CT scans, and graded by the Lequesne MG behavioral score and the Mankin score. TNF-α and IL-1β levels in the synovial fluid of the knee were measured by the enzyme-linked immunosorbent assay (ELISA). Expression levels of MMP-13 and COL-II in the knee cartilage were detected by Western blotting and qRT-PCR.
RESULTS
The Lequesne MG behavioral score and the Mankin score were significantly higher in the model group than those in the control group (P < 0.05). Rabbits in the SH, PRP and UCB-MNC groups had sequentially lower scores than those in the model group. Imaging features of KOA were more pronounced in the model group than in the remaining groups. CB-MNC significantly relieved KOA, compared to SH and PRP. Significantly higher levels of TNF-α and IL-1β in the synovial fluid of the knee, and up-regulated MMP-13 and down-regulated COL-II in the knee cartilage were detected in the model group than in the control group. These changes were significantly reversed by the treatment with SH, PRP and UCB-MNCs, especially UCB-MNCs.
CONCLUSION
Injections of UCB-MNCs into knees protect the articular cartilage and hinder the progression of KOA in rabbits by improving the local microenvironment at knee joints.
Topics: Animals; Rabbits; Osteoarthritis, Knee; Fetal Blood; Disease Models, Animal; Male; Leukocytes, Mononuclear; Interleukin-1beta; Tumor Necrosis Factor-alpha; Synovial Fluid; Platelet-Rich Plasma; Cord Blood Stem Cell Transplantation; Random Allocation
PubMed: 38811966
DOI: 10.1186/s13018-024-04815-8 -
BMC Musculoskeletal Disorders May 2024Osteonecrosis of the femoral head (ONFH) is a common clinical disease. Improper treatment can lead to femoral head collapse and hip joint dysfunction. Core decompression... (Review)
Review
BACKGROUND
Osteonecrosis of the femoral head (ONFH) is a common clinical disease. Improper treatment can lead to femoral head collapse and hip joint dysfunction. Core decompression is particularly important for early ONFH. However, subtrochanteric fractures after core decompression cause some clinical problems.
CASE PRESENTATION
This article describes a 34-year-old male patient with early ONFH. After core decompression, he suffered a subtrochanteric fracture of the femur while bearing weight on the affected limb when going up stairs. He was subsequently treated with open reduction and intramedullary nail fixation.
CONCLUSION
When core decompression is used to treat ONFH, the location or size of the drill hole, whether a tantalum rod or bone is inserted, and partial weight-bearing of the affected limb may directly affect whether a fracture occurs after surgery. It is hoped that this case report can provide a reference for clinical orthopedic surgeons in the treatment of early ONFH.
Topics: Humans; Male; Adult; Decompression, Surgical; Femur Head Necrosis; Hip Fractures; Fracture Fixation, Intramedullary; Treatment Outcome; Postoperative Complications
PubMed: 38811923
DOI: 10.1186/s12891-024-07536-5 -
BMC Geriatrics May 2024Recent genetic evidence supports a causal role for sarcopenia in osteoarthritis, which may be mediated by the occurrence of obesity or changes in circulating...
BACKGROUND
Recent genetic evidence supports a causal role for sarcopenia in osteoarthritis, which may be mediated by the occurrence of obesity or changes in circulating inflammatory protein levels. Here, we leveraged publicly available genome-wide association study data to investigate the intrinsic causal relationship between sarcopenia, obesity, circulating inflammatory protein levels, and osteoarthritis.
METHODS
In this study, we used Mendelian randomization analyses to explore the causal relationship between sarcopenia phenotypes (Appendicular lean mass [ALM], Low hand-grip strength [LHG], and usual walking pace [UWP]) and osteoarthritis (Knee osteoarthritis [KOA], and Hip osteoarthritis [HOA]). Univariable Mendelian randomization (UVMR) analyses were performed using the inverse variance weighted (IVW) method, MR-Egger, weighted median method, simple mode, and weighted mode, with the IVW method being the primary analytical technique. Subsequently, the independent causal effects of sarcopenia phenotype on osteoarthritis were investigated using multivariate Mendelian randomization (MVMR) analysis. To further explore the mechanisms involved, obesity and circulating inflammatory proteins were introduced as the mediator variables, and a two-step Mendelian randomization analysis was used to explore the mediating effects of obesity and circulating inflammatory proteins between ALM and KOA as well as the mediating proportions.
RESULTS
UVMR analysis showed a causal relationship between ALM, LHG, UWP and KOA [(OR = 1.151, 95% CI: 1.087-1.218, P = 1.19 × 10, P = 7.14 × 10) (OR = 1.215, 95% CI: 1.004-1.470; P = 0.046, P = 0.055) (OR = 0.503, 95% CI: 0.292-0.867; P = 0.013, P = 0.027)], and a causal relationship between ALM, UWP and HOA [(OR = 1.181, 95% CI: 1.103-1.265, P = 2.05 × 10, P = 6.15 × 10) (OR = 0.438, 95% CI: 0.226-0.849, P = 0.014, P = 0.022)]. In the MVMR analyses adjusting for confounders (body mass index, insomnia, sedentary behavior, and bone density), causal relationships were observed between ALM, LHG, UWP and KOA [(ALM: OR = 1.323, 95%CI: 1.224- 1.431, P = 2.07 × 10), (LHG: OR = 1.161, 95%CI: 1.044- 1.292, P = 0.006), (UWP: OR = 0.511, 95%CI: 0.290- 0.899, P = 0.020)], and between ALM and HOA (ALM: OR = 1.245, 95%CI: 1.149- 1.348, P = 7.65 × 10). In a two-step MR analysis, obesity was identified to play a potential mediating role in ALM and KOA (proportion mediated: 5.9%).
CONCLUSIONS
The results of this study suggest that decreased appendicular lean mass, grip strength, and walking speed increase the risk of KOA and decreased appendicular lean mass increases the risk of HOA in patients with sarcopenia in a European population. Obesity plays a mediator role in the occurrence of KOA due to appendicular lean body mass reduction.
Topics: Humans; Mendelian Randomization Analysis; Sarcopenia; Obesity; Genome-Wide Association Study; Osteoarthritis, Hip; Aged; Hand Strength; Male; Osteoarthritis, Knee; Female; Osteoarthritis; Multivariate Analysis; Phenotype
PubMed: 38811889
DOI: 10.1186/s12877-024-05098-8 -
Scientific Reports May 2024Meniscus pathologies (damage, extrusion) and synovitis are associated with knee osteoarthritis (KOA); however, whether synovitis mediates the relationship between... (Observational Study)
Observational Study
Meniscus pathologies (damage, extrusion) and synovitis are associated with knee osteoarthritis (KOA); however, whether synovitis mediates the relationship between meniscus pathologies and KOA radiographic progression remains unclear. We conducted an observational study in the Osteoarthritis Initiative (OAI) cohort, with a 48-month follow-up. Meniscus pathology and synovitis were measured by MRI osteoarthritis knee score (MOAKS) at baseline and 24 months, and a comprehensive synovitis score was calculated using effusion and Hoffa synovitis scores. The knee osteoarthritis radiographic progression was considered that Kellgren-Lawrence (KL) grade and joint space narrowing (JSN) grade at 48 months were increased compared to those at baseline. This study included a total of 589 participants, with KL grades mainly being KL1 (26.5%), KL2 (34.1%), and KL3 (30.2%) at baseline, while JSN grades were mostly 0 at baseline. A logistic regression model was used to analyze the relationship between meniscus pathology, synovitis, and KOA progression. Mediation analysis was used to evaluate the mediation effect of synovitis. The average age of the participants was 61 years old, 62% of which were female. The medial meniscus extrusion was longitudinally correlated with the progression of KL (odds ratio [OR]: 2.271, 95% confidence interval [CI]: 1.412-3.694) and medial JSN (OR: 3.211, 95% CI: 2.040-5.054). Additionally, the longitudinal correlation between medial meniscus damage and progression of KOA (OR: 1.853, 95% CI: 1.177-2.941) and medial JSN (OR: 1.655, 95% CI: 1.053-2.602) was significant. Synovitis was found to mediate the relationship between medial meniscus extrusion and KL and medial JSN progression at baseline (β: 0.029, 95% CI: 0.010-0.053; β: 0.022, 95% CI: 0.005-0.046) and beyond 24 months (β: 0.039, 95% CI: 0.016-0.068; β: 0.047, 95% CI: 0.020-0.078). However, we did not find evidence of synovitis mediating the relationship between meniscal damage and KOA progression. Synovitis mediates the relationship between medial meniscus extrusion (rather than meniscus damage) and KOA progression.
Topics: Humans; Synovitis; Osteoarthritis, Knee; Female; Male; Middle Aged; Disease Progression; Aged; Magnetic Resonance Imaging; Menisci, Tibial; Meniscus; Radiography; Knee Joint
PubMed: 38811752
DOI: 10.1038/s41598-024-63291-6 -
Brazilian Journal of Medical and... 2024Osteoarthritis (OA) is a highly prevalent joint disorder characterized by progressive degeneration of articular cartilage, subchondral bone remodeling, osteophyte...
Osteoarthritis (OA) is a highly prevalent joint disorder characterized by progressive degeneration of articular cartilage, subchondral bone remodeling, osteophyte formation, synovial inflammation, and meniscal damage. Although the etiology of OA is multifactorial, pro-inflammatory processes appear to play a key role in disease pathogenesis. Previous studies indicate that electroacupuncture (EA) exerts chondroprotective, anti-inflammatory, and analgesic effects in preclinical models of OA, but the mechanisms underlying these potential therapeutic benefits remain incompletely defined. This study aimed to investigate the effects of EA on OA development in a rat model, as well as to explore associated molecular mechanisms modulated by EA treatment. Forty rats were divided into OA, EA, antagomiR-214, and control groups. Following intra-articular injection of monosodium iodoacetate to induce OA, EA and antagomiR-214 groups received daily EA stimulation at acupoints around the knee joint for 21 days. Functional pain behaviors and chondrocyte apoptosis were assessed as outcome measures. The expression of microRNA-214 (miR-214) and its downstream targets involved in apoptosis and nociception, BAX and TRPV4, were examined. Results demonstrated that EA treatment upregulated miR-214 expression in OA knee cartilage. By suppressing pro-apoptotic BAX and pro-nociceptive TRPV4, this EA-induced miR-214 upregulation ameliorated articular pain and prevented chondrocyte apoptosis. These findings suggested that miR-214 plays a key role mediating EA's therapeutic effects in OA pathophysiology, and represents a promising OA treatment target for modulation by acupuncture.
Topics: Animals; TRPV Cation Channels; MicroRNAs; Electroacupuncture; Apoptosis; Male; Osteoarthritis; Chondrocytes; Disease Models, Animal; bcl-2-Associated X Protein; Rats, Sprague-Dawley; Rats
PubMed: 38808885
DOI: 10.1590/1414-431X2024e13238