A systematic review of the use of shockwave therapy for knee osteoarthritis.

Introduction: Previous studies assessed the effect of extracorporeal shockwave therapy (ESWT) for knee osteoarthritis (OA) among different situations. Thus, results from a meta-analysis regarding this topic may not be reliable due to heterogeneity. Methods: A systematic review was conducted on three internet databases, namely Cochrane Library, PubMed, and Embase, gathering pertinent papers from their establishment to March 2024. The search phrases were as follows: "shockwave" OR "shock wave" OR "extracorporeal shockwave" OR "Extracorporeal Shockwave Therapy [MeSH Term]" AND "knee" AND ("osteoarthritis" OR "arthritis" OR "arthritic" OR "osteoarthritis [MeSH term]"). Results: Twenty-four articles (n = 888) were included, with the resulting conclusions demonstrating that ESWT was effective for knee OA compared with sham ESWT; however, ESWT was not effective for patients with severe knee OA. Patients receiving higher energy or higher shock number had significant improvement than those receiving lower energy or less shock number, respectively. Adding ESWT in isokinetic muscular strengthening exercises (IMSE) was more effective than IMSE alone. The efficacy of ESWT was better than other therapies, including intravenously applied prostacyclin and bisphosphonate, corticosteroid injection, kinesiotherapy, hyaluronic acid injection, platelet-rich plasma injection, and physiotherapy. Conclusions: This review demonstrated that ESWT was effective for knee OA. Higher energy and more shock numbers could obtain better efficacy. ESWT could be used as a replacement for some other therapies.

Extracorporeal shockwave therapy in the management of knee osteoarthritis: A systematic review of dose-response meta-analysis.

Introduction: The aim of the research was to conduct a systematic review of dose-response meta-analysis, examining the correlation between the energy of extracorporeal shockwave therapy (ESWT) and clinical outcomes for patients with knee osteoarthritis (OA). Methods: We conducted a systematic review of three online databases - PubMed, Embase, and Cochrane Library - to collect relevant articles from their inception to May 2023. We included the articles that investigated the efficacy of ESWT in treating knee OA and were designed using randomized controlled trials (RCTs). The main outcomes were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for primary outcomes and the Visual Analog Scale (VAS) for secondary outcomes. We conducted a dose-response meta-analysis to examine the correlation between the energy of ESWT and clinical outcomes. Results: Our study included a total of 7 RCTs (comprising 450 subjects) that met the inclusion criteria. We found a negative linear relationship between the doses of ESWT and WOMAC scores at the 1-week (p = 0.0398) and 4-week (p = 0.001) follow-up periods, but not at the 12-week follow-up period (p = 0.202). Furthermore, at the 4-week (p = 0.0477) and 12-week (p < 0.001) follow-up periods, a negative linear connection was found between the ESWT dose and VAS scores, but not at the 1-week follow-up period (p = 0.2268). Conclusions: Our results demonstrate a dose-response connection between the energy of ESWT and clinical outcomes. This suggests that using higher energy levels of ESWT to treat knee OA could lead to greater improvement in clinical outcomes compared to using lower energy levels.

Comparison of distal radius fracture plating surgery under wide-awake local anesthesia no tourniquet technique and balanced anesthesia: a retrospective cohort study.

BACKGROUND: Distal radius fractures (DRF) are frequently treated with internal fixation under general anesthesia or a brachial plexus block. Recently, the wide-awake local anesthesia with no tourniquet (WALANT) technique has been suggested as a method that results in higher patient satisfaction. This study aimed to evaluate the functional outcomes, complications, and patient-reported outcomes of DRF plating surgery under both the WALANT and balanced anesthesia (BA). METHODS: Ninety-three patients with DRFs who underwent open reduction and plating were included. Regarding the anesthetic technique, 38 patients received WALANT, while 55 received BA, comprised of multimodal pain control brachial plexus anesthesia with light general support. The patient's overall satisfaction in both groups and the intraoperative numerical rating scale of pain and anxiety (0-10) in the WALANT group were recorded. The peri-operative radiographic parameters were measured; the clinical outcomes, including Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, wrist mobility, and grip strength, were recorded in up to 1-year follow-up. Results presented with a mean difference and 95% confidence intervals and mean ± standard deviation. RESULTS: The mean age of patients in the WALANT group was higher than in the BA group (63 ± 17 vs. 54 ± 17, P = 0.005), and there were fewer intra-articular DRF fractures in the WALANT group than in the BA group (AO type A/B/C: 30/3/5 vs. 26/10/19, P = 0.009). The reduction and plating quality were similar in both groups. The clinical outcomes at follow-up were comparable between the two groups, except the WALANT group had worse postoperative 3-month pronation (88% vs. 96%; - 8.0% [ - 15.7 to - 0.2%]) and 6-month pronation (92% vs. 100%; - 9.1% [ - 17.0 to - 1.2%]), and better postoperative 1-year flexion (94% vs. 82%; 12.0% [2.0-22.1%]). The overall satisfaction was comparable in the WALANT and BA groups (8.7 vs. 8.5; 0.2 [ - 0.8 to 1.2]). Patients in the WALANT group reported an injection pain scale of 1.7 ± 2.0, an intraoperative pain scale of 1.2 ± 1.9, and an intraoperative anxiety scale of 2.3 ± 2.8. CONCLUSION: The reduction quality, functional outcomes, and overall satisfaction were comparable between the WALANT and BA groups. With meticulous preoperative planning, the WALANT technique could be an alternative for DRF plating surgery in selected patients. Trial registration This retrospective study was approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-E(I)-20210201).

Suramin ameliorates osteoarthritis by acting on the Nrf2/HO-1 and NF-κB signaling pathways in chondrocytes and promoting M2 polarization in macrophages.

Osteoarthritis (OA)-the most prevalent of arthritis diseases-is a complicated pathogenesis caused by cartilage degeneration and synovial inflammation. Suramin has been reported to enhance chondrogenic differentiation. However, the therapeutic effect of suramin on OA-induced cartilage destruction has remained unclear. Suramin is an anti-parasitic drug that has potent anti-purinergic properties. This study investigated the protective effects and underlying mechanisms of suramin on articular cartilage degradation using an in vitro study and mice model with post-traumatic OA. We found that suramin markedly suppressed the IL-1ß increased expression of matrix destruction proteases-such as ADAMT4, ADAMTS5, MMP3, MMP13, and inflammatory mediators-including the iNOS, COX2, TNFα, and IL-1ß; while greatly enhancing the synthesis of cartilage anabolic factors-such as COL2A1, Aggrecan and SOX9 in IL-1ß-induced porcine chondrocytes. In vivo experiments showed that intra-articular injection of suramin ameliorated cartilage degeneration and inhibited synovial inflammation in an anterior cruciate ligament transection (ACLT)-induced OA mouse model. In mechanistic studies, we found that exogenous supplementation of suramin can activate Nrf2, and accordingly inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB) and mitogen-activated protein kinase (MAPK) pathways, thereby alleviating the inflammation and ECM degeneration of chondrocytes stimulated by IL-1ß. In addition, suramin also repolarized M1 macrophages to the M2 phenotype, further reducing the apoptosis of chondrocytes. Collectively, the results of the study suggests that suramin is a potential drugs which could serve as a facilitating drug for the application of OA therapy toward clinical treatment.

Suramin enhances chondrogenic properties by regulating the p67phox/PI3K/AKT/SOX9 signalling pathway.

AIMS: Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. METHODS: Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1ß; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67phox was involved in suramin-enhanced chondrocyte phenotype maintenance. RESULTS: Suramin enhanced the COL2A1 and ACAN expression and lowered COL1A1 synthesis. Also, in 3D pellet culture GAG and COL2A1 production was significantly higher in pellets consisting of chondrocytes expanded with suramin compared to controls. Surprisingly, suramin also increased ROS generation, which is largely caused by enhanced NOX (p67phox) activity and membrane translocation. Overexpression of p67phox but not p67phoxAD (deleting amino acid (a.a) 199 to 212) mutant, which does not support ROS production in chondrocytes, significantly enhanced chondrocyte phenotype maintenance, SOX9 expression, and AKT (S473) phosphorylation. Knockdown of p67phox with its specific short hairpin (sh) RNA (shRNA) abolished the suramin-induced effects. Moreover, when these cells were treated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor LY294002 or shRNA of AKT1, p67phox-induced COL2A1 and ACAN expression was significantly inhibited. CONCLUSION: Suramin could redifferentiate dedifferentiated chondrocytes dependent on p67phox activation, which is mediated by the PI3K/AKT/SOX9 signalling pathway.Cite this article: Bone Joint Res 2022;11(10):693-708.

Efficacy of Prenatal Yoga in the Treatment of Depression and Anxiety during Pregnancy: A Systematic Review and Meta-Analysis.

Women commonly suffer from depression during pregnancy. For reducing depression, yoga seems to be more suitable for pregnant women than other physical activities because of its low exercise intensity. The objective of this study was to assess the efficacy of prenatal yoga on the treatment of depression during pregnancy. Three electronic databases were searched for relevant articles from their inception to May 2021, including PubMed, Cochrane Library, and ScienceDirect. Pre- and post-test outcomes were adopted to estimate standardized mean difference with a 95% confidence interval for assessing the efficacy of yoga. Heterogeneity among articles was detected using I2 value. A total of 13 articles that contained 379 subjects were included for meta-analysis. No significant improvement in depression scores after practicing yoga was observed for women without depression (p = 0.09) but significant improvement was observed for women with depression (p = 0.001). Although significant improvement in anxiety scores after yoga was observed for women without depression (p = 0.02), the results of the sensitivity analysis were not consistent, while significant improvement in anxiety scores after yoga was also observed for women with depression (p < 0.00001). The current evidence has suggested that yoga had significant improvement in depression and anxiety scores in pregnant women with depression. However, the level of evidence of this study was not high. More articles with high levels of evidence should be conducted to confirm our conclusion in the future.

Analgesic effects of sterile water injection in the management of low back pain during labor: A systematic review and meta-analysis.

BACKGROUND: Sterile water injections (SWIs) as a non-pharmacologic and cost-effective method have been adopted to relieve low back labor pain (LBLP). OBJECTIVE: To compare the efficacy of intradermal and subdermal SWIs in the treatment of LBLP. SEARCH STRATEGY: Three databases (PubMed, Cochrane Library, and ScienceDirect) were searched to find relevant articles using two terms, "labor" and "sterile water". SELECTION CRITERIA: Studies reporting women with LBLP treated by intradermal or subdermal SWIs in the low back area were included. DATA COLLECTION AND ANALYSIS: Mean differences with 95% confidence interval (CI) and relative risk with 95% CI were used to estimate VAS score and cesarean section rate, respectively. MAIN RESULTS: Except for 10 min, the patients in the intradermal or subdermal SWI group experienced considerable pain reduction compared with the control group for 30-45, 60, and 90 min. Directly comparing intradermal and subdermal SWI groups, the subdermal injection group had significantly better pain relief than the intradermal injection group only at 10 min after treatment. CONCLUSIONS: Both intradermal and subdermal SWIs could reduce LBLP at 30-90 min. The subdermal SWI had significantly better LBLP relief than the intradermal injection only at 10 min after treatment.

Arthroscopic Partial Trapeziectomy for Thumb Carpometacarpal Joint Osteoarthritis: 5-Year Follow-up.

Osteoarthritis of the thumb carpometacarpal (CMC) joint is the most common type of arthritis of the hand. The goal of the study was to evaluate clinical results and radiographic changes after arthroscopic partial trapeziectomy combined with ligament shrinkage and K-wire fixation to treat thumb CMC joint arthritis. From February 2013 to March 2014, 24 patients with thumb CMC joint arthritis received this arthroscopic procedure. We investigated the preoperative and postoperative Modified Mayo Wrist Score (MMWS); Disabilities of the Arm, Shoulder and Hand (DASH) score; radiographic changes; and associated complications. Sixteen patients completed 5 years of functional score and radiographic follow-up. Comparison of preoperative and postoperative MMWS and DASH scores showed significant improvement after the arthroscopic procedure. Pre-operative and postoperative evaluation of radiographic changes showed significant differences in the CMC joint distance, scaphoid-metacarpal distance, trapezium-metacarpal distance, and metacarpal prominence distance. This arthroscopic procedure is an effective and less invasive method for the treatment of CMC joint arthritis. This procedure can improve clinical function, preserve the mechanical height of the trapezium, and increase CMC joint space. We report our surgical technique and some pitfalls that required attention during the arthroscopic procedure. [Orthopedics. 2022;45(3):e140-e147.].

The Er:YAG vaginal laser for management of women with genitourinary syndrome of menopause (GSM).

The purpose of our study was to investigate the effects of vulvovaginal erbium laser on the genitourinary syndrome of menopause (GSM) and sexual function of postmenopausal women. We conducted a retrospective study of sixty-four postmenopausal women with GSM, and these patients were scheduled for three times of vulvovaginal erbium laser treatment. A baseline and post-treatment vaginal status was assessed by measuring vaginal pH, patients' subjective vulvovaginal atrophy (VVA) symptoms, which included dryness, dyspareunia, itching, and burning. The urinary response to treatment was assessed using ICIQ-SF, UDI-6, IIQ-7, OABSS, and POPDI-6. Sexual function was evaluated using the Female Sexual Function Index (FSFI) before and after vulvovaginal laser therapy. Patient follow-ups were scheduled for 12 months after treatment. A total of sixty-four patients were enrolled in the study. We observed the significant improvement in the percentage of negative symptoms (dryness/dyspareunia/itching/burning) and in lower urinary tracts symptoms evaluated with ICIQ-SF, UDI-6, IIQ-7, OABSS, and POPDI-6 (P < 0.05). Patients' overall satisfaction regarding their sexual life, assessed via Female Sexual Function Index (FSFI), showed significant improvement in its six domains of sexual function (P < 0.05). The pH level of vaginal secretions significantly decreased. No long-term complications were found post-treatment. The Er:YAG vaginal laser procedure is associated with a significant improvement in GSM and sexual function of postmenopausal women. Our result demonstrates that it can be a safe and efficacious treatment for patients with GSM without any serious adverse effects up to 1-year post-treatment. The long-term effects of using vulvovaginal laser in the treatment of GSM should be investigated.

Zonal-Layered Chondrocyte Sheets for Repairment of Full-Thickness Articular Cartilage Defect: A Mini-Pig Model.

The cell sheet technique is a promising approach for tissue engineering, and the present study is aimed to determine a better configuration of cell sheets for cartilage repair. For stratified chondrocyte sheets (S-CS), articular chondrocytes isolated from superficial, middle, and deep zones were stacked accordingly. Heterogeneous chondrocyte sheets (H-CS) were obtained by mixing zonal chondrocytes. The expressions of chondrocytes, cytokine markers, and glycosaminoglycan (GAG) production were assessed in an in vitro assay. The curative effect was investigated in an in vivo porcine osteochondral defect model. The S-CS showed a higher cell viability, proliferation rate, expression of chondrogenic markers, secretion of tissue inhibitor of metalloproteinase, and GAG production level than the H-CS group. The expressions of ECM destruction enzyme and proinflammatory cytokines were lower in the S-CS group. In the mini-pigs articular cartilage defect model, the S-CS group had a higher International Cartilage Repair Society (ICRS) macroscopic score and displayed a zonal structure that more closely resembled the native cartilage than those implanted with the H-CS. Our study demonstrated that the application of the S-CS increased the hyaline cartilage formation and improved the surgical outcome of chondrocyte implication, offering a better tissue engineering strategy for treating articular cartilage defects.

Hybrid versus total sublaminar wires in patients with spinal muscular atrophy undergoing scoliosis surgery.

BACKGROUND: Early versions of spinal muscular atrophy (SMA) scoliosis correction surgery often involved sublaminar devices. Recently, the utilization of pedicle screws has gained much popularity. Pedicle screws are generally believed to provide additional deformity correction, but pedicle size and rotational deformity limit their application in the thoracic spine, resulting in a hybrid construct involving pedicle screws and sublaminar wire. Studies of the efficacy of hybrid instrumentation in SMA scoliosis are often limited by the scarcity of the disease itself. In this study, we aimed to compare the surgical outcomes between hybrid constructs involving pedicle screws and sublaminar wire and sublaminar wire alone in patients with SMA scoliosis. METHODS: We retrospectively reviewed the clinical records and radiographic assessments of patients with SMA scoliosis who underwent corrective surgery between 1993 and 2017. The radiographic assessments included deformity correction and progressive changes in the major curve angle, pelvic tilt (PT) and coronal balance (CB). The correction of deformities was observed postoperatively and at the patient's 2-year follow-up to test the efficacy of each type of construct. RESULTS: Thirty-three patients were included in this study. There were 14 and 19 patients in the wiring and hybrid construct groups, respectively. The hybrid construct group demonstrated a higher major curve angle correction (50.5° ± 11.2° vs. 36.4° ± 8.4°, p < 0.001), a higher apical vertebral rotation correction (10.6° ± 3.9° vs. 4.8° ± 2.6°, p < 0.001), and a reduced progression of the major curve angle at the 2-year follow-up (5.1° ± 2.9° vs. 8.7° ± 4.8°, p < 0.001). A moderate correlation was observed between the magnitude of correction of the apical vertebral rotation angle and the major curve (r = 0.528, p = 0.002). CONCLUSION: This study demonstrated that hybrid instrumentation can provide a greater magnitude of correction in major curve and apical rotation as well as less major curve progression than sublaminar wire instrumentation alone in patients with SMA scoliosis. Level of evidence III.

A New Strategy for Rapid Diagnosis of the Source of Low Back Pain in Patients Scheduled to Undergo Treatment with Cooled Radiofrequency Ablation.

OBJECTIVE: The objective of this study was to develop a new strategy for rapid diagnosis of the source of low back pain (LBP) for treatment with cooled radiofrequency ablation (RFA). MATERIALS: Patients suffering from facet joint (FJ) or sacroiliac joint (SIJ) pain for more than 3 months were included. Two methods, Technetium Tc99m methylene diphosphonate single photon emission tomography/computed tomography (99mTc-MDP SPECT/CT) and a modified Fortin finger test were used to identify the source of LBP for treatment with cooled RFA. The visual analog scale (VAS) and Oswestry disability index (ODI) were used to assess the patients' pain levels and disabilities respectively. These two measures were recorded at baseline and 1-week, 1-month, 3-month, and 6-month follow-up visits. RESULTS: A total of 40 patients with LBP were included in this study. Our results demonstrated that the patients with LBP identified by our new strategy had significant improvements in VAS or ODI score at 1-week to 6-month follow-up visits (p < 0.001) after receiving cooled RFA. Similar results were also found in patients with FJ pain and those with FJ and SIJ pain respectively. Among all the patients, over 70% had greater than or equal to 50% reduction in VAS and ODI scores. No serious adverse events were observed after treatment. CONCLUSIONS: This new strategy could be successfully adopted for rapid diagnosis of the source of comprehensive LBP.

Intravenous Tranexamic Acid Reduces Blood Loss and Transfusion Volume in Scoliosis Surgery for Spinal Muscular Atrophy: Results of a 20-Year Retrospective Analysis.

Intravenous tranexamic acid (TXA) has been administered to reduce intraoperative blood loss in scoliosis surgery. However, the therapeutic effect of TXA on spinal muscular atrophy (SMA) scoliosis surgery is not well demonstrated. Therefore, this study aimed to assess the efficacy of intravenous TXA in SMA scoliosis surgery. From December 1993 to August 2020, 30 SMA patients who underwent scoliosis surgery (posterior fusion with fusion level of thoracic second or third to pelvis) were retrospectively enrolled and divided into the TXA group and non-TXA (control) group, with 15 patients in each group. Survey parameters were the amount of blood loss, blood transfusion, crystalloid transfusion volume, intubation time, and associated pulmonary complications (including pneumonia, pulmonary edema, and pulmonary atelectasis). The TXA group had significantly lesser blood loss than the control group (p = 0.011). Compared with the control group, the TXA group had significantly lower blood transfusion (p < 0.001), crystalloid volume (p = 0.041), and total transfusion volume (p = 0.005). In addition, the TXA group had fewer postoperative pulmonary complications, and patients with pulmonary complications were associated with a higher relative crystalloid volume and relative total transfusion volume (p = 0.003 and 0.022, respectively). In conclusion, TXA can be effective in reducing intraoperative blood loss and crystalloid fluid transfusions during scoliosis surgery in SMA patients, which may aid in reducing postoperative pulmonary complications.

Pain Control Affects the Radiographic Diagnosis of Segmental Instability in Patients with Degenerative Lumbar Spondylolisthesis.

BACKGROUND: Diagnosing intervertebral instability is crucial for the treatment of degenerative lumbar spondylolisthesis (DLS). Disabling back pain will reduce spinal mobility which leads to an underestimate of the incidence of intervertebral instability. We hypothesized that adequate analgesia could alter the flexion/extension exam performance, and thus increase the diagnostic accuracy of segmental instability. MATERIALS AND METHODS: One hundred patients with low-grade DLS were prospectively enrolled in the before-after cohort study. Standing lateral flexion/extension radiographs of lumbar spines were examined and analyzed before and after intramuscular injections of 30 mg ketorolac. RESULTS: Pain score decreased significantly after analgesic injections (p < 0.001). Dynamic slip (DS), dynamic segmental angle (DA), dynamic lumbar lordosis, and slip percentage (SP) were significantly increased after pain reduction (all p < 0.001). According to the diagnostic criteria for segmental instability (DS > 4.5 mm, DA > 15°, or SP > 15%), there were 4%, 4%, and 0.7% of total motion segments fulfilling the criteria which markedly increased to 42%, 32%, and 16.7% after analgesia was administered. The incidence of instability also increased from 6% to 38% after analgesia. CONCLUSIONS: The diagnosis rate of intervertebral instability is commonly underestimated in the presence of low back pain. This short-term pain relief facilitates reliable functional imaging adding to the diagnosis of intervertebral instability.

Suramin attenuates intervertebral disc degeneration by inhibiting NF-κB signalling pathway.

AIMS: Interleukin (IL)-1ß is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. METHODS: Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1ß, 10 µM suramin, or 10 µM suramin plus IL-1ß. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining. RESULTS: Suramin inhibited IL-1ß-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1ß-treated NP cells. IL-1ß-induced inflammation, assessed by IL-1ß, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1ß-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments. CONCLUSION: Suramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells. Cite this article: Bone Joint Res 2021;10(8):498-513.

Shockwave Treatment Enhanced Extracellular Matrix Production in Articular Chondrocytes Through Activation of the ROS/MAPK/Nrf2 Signaling Pathway.

OBJECTIVE: Shockwave application is a potential treatment for osteoarthritis (OA), but the underlying mechanism remains unknown. Oxidative stress and a counterbalancing antioxidant system might be the key to understanding this mechanism. We hypothesized that reactive oxygen species (ROS) and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2),which is an important regulator of cellular redox homeostasis, are plausible elements. DESIGN: Porcine chondrocytes were cultured in a 3-dimensional pellet model and subjected to shockwaves. The effects of shockwaves with various energy-flux densities on optimal extracellular matrix (ECM) synthesis were assessed. ROS, mitogen-activated protein kinase (MAPK) signaling, and the redox activity of Nrf2 were measured. To investigate the signaling mechanism involved in the shockwave treatment in chondrocytes, specific inhibitors of ROS, MAPK signaling, and Nrf2 activity were targeted. RESULTS: Shockwaves increased ECM synthesis without affecting cell viability or proliferation. Furthermore, they induced transient ROS production mainly through xanthine oxidase. The phosphorylation of ERK1/2 and p38 and the nuclear translocation of Nrf2 were activated by shockwaves. By contrast, suppression of ROS signaling mitigated shockwave-induced MAPK phosphorylation, Nrf2 nuclear translocation, and ECM synthesis. Pretreatment of chondrocytes with the specific inhibitors of MEK1/2 and p38, respectively, mitigated the shockwave-induced nuclear translocation of Nrf2 and ECM synthesis. Nrf2 inhibition by both small hairpin RNA knockdown and brusatol reduced the shockwave-enhanced ECM synthesis. CONCLUSIONS: Shockwaves activated Nrf2 activity through the induction of transient ROS signaling and subsequently enhanced ECM synthesis in chondrocytes. This study provided fundamental evidence confirming the potential of shockwaves for OA management.

Comparison of Efficacy among Three Radiofrequency Ablation Techniques for Treating Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

Radiofrequency ablation (RFA) was first introduced for treating knee osteoarthritis (OA) in 2010 and has emerged as a minimally invasive treatment option. Three RFA techniques have been adopted for treating knee OA, including conventional, pulsed, and cooled RFA. However, the efficacy among different RFA techniques in the treatment of knee OA is still unclear. Three electronic databases were systematically searched for relevant articles, including PubMed, Embase, and Cochrane Library. A meta-analysis of articles that investigated the use of RFA techniques in the treatment of knee OA was conducted to pool the effect size in pain before and after treatment. A total of 20 eligible articles (including 605 patients) were included for our meta-analysis. After treatment, the patients had significant improvements in pain for all three RFA techniques when compared with the baseline level for the 1, 3-, and 6-month follow-ups (p < 0.00001). However, there were no significant differences in the efficacy among the three RFA techniques for all follow-up visits (p > 0.05). The three RFA techniques demonstrated a significant improvement in pain for up to 6 months after treatment. Comparing the efficacy of the three RFA techniques in the treatment of knee OA, our results showed that no significant differences in pain relief among the three RFA techniques were observed at the 1-, 3-, 6, and 12-month follow-up visits.

Effect of Freshly Isolated Bone Marrow Mononuclear Cells and Cultured Bone Marrow Stromal Cells in Graft Cell Repopulation and Tendon-Bone Healing after Allograft Anterior Cruciate Ligament Reconstruction.

Graft cell repopulation and tendon-bone tunnel healing are important after allograft anterior cruciate ligament reconstruction (ACLR). Freshly isolated bone marrow mononuclear cells (BMMNCs) have the advantage of short isolation time during surgery and may enhance tissue regeneration. Thus, we hypothesized that the effect of intra-articular BMMNCs in post-allograft ACLR treatment is comparable to that of cultured bone marrow stromal cells (BMSCs). A rabbit model of hamstring allograft ACLR was used in this study. Animals were randomly assigned to the BMMNC, BMSC, and control groups. Fresh BMMNCs isolated from the iliac crest during surgery and cultured BMSCs at passage four were used in this study. A total of 1 × 107 BMMNCs or BMSCs in 100 µL phosphate-buffered saline were injected into the knee joint immediately after ACLR. The control group was not injected with cells. At two and six weeks post operation, we assessed graft cell repopulation with histological and cell tracking staining (PKH26), and tendon-bone healing with histological micro-computed tomography and immunohistochemical analyses for collagen I and monocyte chemoattractant protein-1 (MCP1). At two weeks post operation, there was no significant difference in the total cell population within the allograft among the three groups. However, the control group showed significantly higher cell population within the allograft than that of BM cell groups at six weeks. Histological examination of proximal tibia revealed that the intra-articular delivered cells infiltrated into the tendon-bone interface. Compared to the control group, the BM cell groups showed broader gaps with interfacial fibrocartilage healing, similar collagen I level, and higher MCP1 expression in the early stage. Micro-CT did not reveal any significant difference among the three groups. BMMNCs and BMSCs had comparable effects on cell repopulation and interfacial allograft-bone healing. Intra-articular BM cells delivery had limited benefits on graft cell repopulation and caused higher inflammation than that in the control group in the early stage, with fibrocartilage formation in the tendon-bone interface after allograft ACLR.