Joint Cartilage Research Articles

The effect of straight leg raise on reducing pain and increasing functional ability of the knee joint in patients with osteoarthritis genu

Background: Osteoarthritis of the genu is one of the most common types of osteoarthritis, especially in the elderly population. This disease causes the destruction of cartilage in the knee joint, leading to pain, stiffness, and decreased functional ability in performing daily activities. Postmenopausal women are more susceptible to osteoarthritis due to hormonal changes that affect bone and muscle health. Muscle strengthening therapy, such as the Straight Leg Raise (SLR), is used as one of the rehabilitation methods to reduce pain and improve functional ability in patients with osteoarthritis genu by strengthening the quadriceps muscles that support the knee. Purpose: To assess how SLR exercise helps patients with knee osteoarthritis by lowering pain and increasing functional abilities. Method: 24 patients were split into treatment and control groups in this quasi-experimental investigation. The Visual Analog Scale (VAS) was used to measure pain, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to measure functional ability. Results: The treatment group showed significant reduction in tenderness and motion pain, as well as increased functional ability compared to the control group. Wilcoxon and Mann-Whitney U tests showed significant differences. Conclusion: SLR exercises are effective in strengthening the quadriceps muscles, reducing pain, and improving knee stability. These results support previous studies on the benefits of strengthening exercises in patients with osteoarthritis.

Marein ameliorates the progression of osteoarthritis: An in vitro and in vivo studies

Osteoarthritis (OA) is a prevalent, degenerative joint disease that requires effective treatments to prevent its progression. Therefore, the development of novel therapeutic strategies to address this unmet clinical challenge is paramount. Marein (MA), the principal active compound of Coreopsis tinctoria Nutt, exhibits anti-inflammatory and anti-oxidant properties in various diseases, indicating its potential as a therapeutic agent for OA. In this study, we assessed the ability of marein to mitigate the inflammatory response in OA and reverse cartilage degradation. The results demonstrated that MA exerted a concentration -dependent effect (10, 25, 50 μM), facilitating the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), reversing the suppression of nuclear factor kappa B (NF-κB) activation, and mitigating the inflammatory response, ultimately alleviating joint cartilage damage. In cellular assays, MA (10, 25, 50 μM) markedly decreased the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-13 (MMP-13) and a metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), simultaneously decreasing reactive oxygen species production by enhancing Nrf2 nuclear translocation. Furthermore, in animal models, MA (50 μM) significantly improved knee joint cartilage damage and effectively reduced OA progression. Further studies are needed to determine the long-term safety and therapeutic potential of MA and to expand its application scope. Moreover, preclinical studies are required to evaluate the efficacy of MA in humans. Overall, MA is a promising therapeutic candidate and may be an effective treatment for patients with OA.

Collagen Hydrolysates as Nutritional Support in Canine Osteoarthritis: A Narrative Review.

Osteoarthritis (OA) is a common disease in dogs with severe impact on their welfare. The multimodal management of OA includes feeding therapeutic diets and nutraceuticals to slow down OA progression. Collagen hydrolysates (CH) are a nutritional supplement that may exert anabolic effects on osteoarthritic joint cartilage as well as disease-modifying effects. After oral intake, CH is absorbed, mainly as amino acids, di- and tripeptides that are transported amongst others to the joint. In addition to reducing cartilage degradation, CH metabolites may reduce synovial inflammation and subchondral bone sclerosis during OA. Preliminary evidence in dogs suffering from the consequences of OA support the clinical efficacy of CH with reported reductions in lameness. However, effects on biomarker level of cartilage metabolism and inflammation are inconclusive. Additionally, current studies show a lack of standardised dosing regimens and the use of not validated outcomes. Future work should therefore elucidate further on the bioavailability of CH in dogs in order to establish adequate dosing recommendations. Furthermore, high-quality placebo-controlled randomised controlled trials are essential to dstudies have evaluated the cetermine the clinical efficacy of CH to reduce lameness, prevent OA progression and thereby improve the level of evidence.

Articular cartilage regeneration with a microgel as a support biomaterial. A rabbit knee model

Articular cartilage has limited regenerative capacity, so focal lesions generate mechanical stress in the joint that induces an aggravation of the damage, which ultimately leads to osteoarthritis. We recently suggested the use of microgels at the site of the cartilage defect, as a support material, to generate a biomechanical environment where pluripotent cells differentiate towards the hyaline cartilage phenotype. Here we propose a chondral regeneration strategy based on subchondral bone injury, and filling the defect site with an agglomerate of two types of microspheres, some rigid made of a biodegradable polyester (40μm mean diameter), and others with a gel consistency made of platelet-rich plasma obtained from circulating blood (70-110μm diameter). A 3-mm diameter defect was made in the articular cartilage of the knee joint in rabbits, exposing the subchondral bone, in which incisions were made to produce bleeding. Microgels were implanted filling the defect, which was covered with a synthetic membrane of the same polyester. Three months later, cartilage regeneration was analyzed according to the International Cartilage Repair Society (ICRS) guidelines. The newly formed tissue showed histological characteristics of hyaline cartilage, being significantly closer to native cartilage than when only the membrane was implanted, mainly in parameters such as tissue (70.0±20.9) and cell morphologies (100.0±0.0), and surface architecture (90.0±22.4) and assessment (70.0±11.2), with native tissue having a value of 100. Polyester microspheres and membrane were not bioreabsorbed during the three months, but rather moved towards the subchondral bone, leaving space for the organization of the newly formed tissue.

Extracellular Vesicles Derived Ectonucleoside Triphosphate Diphosphohydrolase 3 Alleviates Mitochondrial Dysfunction of Osteoarthritis Chondrocytes via Ectonucleotide Pyrophosphatase/Phosphodiesterase 1-Induced Suppression of the AKT/Notch2 Pathway.

Osteoarthritis (OA) is the most common joint disease that usually starts from joint cartilage injury. Notch2, a versatile signaling in human development and diseases, was recently uncovered to be an important regulator in chondrocyte damage. However, in OA chondrocytes, how Notch2 activation is dysregulated is largely unknown. Here, integrated bioinformatic analysis was performed on GEO datasets (GSE199193 and GSE224255) to search potential extracellular vesicles (EVs) derived regulators of Notch2 in OA chondrocytes. Ectonucleoside triphosphate diphosphohydrolase 3 (Entpd3), a most differentially expressed gene both in LPS-induced macrophage EV and Notch2 mutant chondrocytes, was screened as the candidate regulator of Notch2 in OA chondrocytes. Gain-of-function experiments in cultured human chondrocytes revealed that recombinant Entpd3 protein and macrophage EV both had a protective effect on LPS-induced inflammation, oxidative stress, apoptosis, and collagen loss in chondrocytes. In terms of mechanism, Entpd3 directly interacted with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and suppressed AKT/Notch2-mediated mitochondrial dysfunction. Finally, we verified that either macrophage EV administration or Entpd3 overexpression was able to alleviate osteoarthritis in mice in vivo. In conclusion, Entpd3 is identified as a new regulator in OA, which alleviates mitochondrial dysfunction induced chondrocyte damage via ENPP1-induced suppression of the AKT/Notch2 pathway.

Impacts of mesenchymal stem cells and hyaluronic acid on inflammatory indicators and antioxidant defense in experimental ankle osteoarthritis.

No effective treatment guarantees full recovery from osteoarthritis (OA), and few therapies have disadvantages. To determine if bone marrow mesenchymal stem cells (BMMSCs) and hyaluronic acid (HA) treat ankle OA in Wistar rats. BMMSCs were characterized using flow cytometry with detection of surface markers [cluster of differentiation 90 (CD90), CD105, CD34, and CD45]. Fifty male Wistar rats were divided into five groups of 10 rats each: Group I, saline into the right tibiotarsal joint for 2 days; Group II, monosodium iodate (MIA) into the same joint; Groups III, MIA + BMMSCs; Group IV, MIA + HA; and Group V, MIA + BMMSCs + HA. BMMSCs (1 × 106 cells/rat), HA (75 µg/rat), and BMMSCs (1 × 106 cells/rat) alongside HA (75 µg/rat) were injected intra-articularly into the tibiotarsal joint of the right hind leg at the end of weeks 2, 3, and 4 after the MIA injection. The elevated right hind leg circumference values in the paw and arthritis clinical score of osteoarthritic rats were significantly ameliorated at weeks 4, 5, and 6. Lipid peroxide significantly increased in the serum of osteoarthritic rats, whereas reduced serum glutathione and glutathione transferase levels were decreased. BMMSCs and HA significantly improved OA. The significantly elevated ankle matrix metalloproteinase 13 (MMP-13) mRNA and transforming growth factor beta 1 (TGF-β1) protein expression, and tumor necrosis factor alpha (TNF-α) and interleukin-17 (IL-17) serum levels in osteoarthritic rats were significantly downregulated by BMMSCs and HA. The effects of BMMSCs and HA on serum TNF-α and IL-17 were more potent than their combination. The lowered serum IL-4 levels in osteoarthritic rats were significantly upregulated by BMMSCs and HA. Additionally, BMMSCs and HA caused a steady decrease in joint injury and cartilage degradation. BMMSCs and/or HA have anti-arthritic effects mediated by antioxidant and anti-inflammatory effects on MIA-induced OA. MMP-13 and TGF-β1 expression improves BMMSCs and/or HA effects on OA in Wistar rats.

Origins of synergy in multilipid lubrication

Lipid bilayers, ubiquitous in living systems, form lubricious boundary layers in aqueous media, with broad relevance for biolubrication, especially in mechanically stressed environments such as articular cartilage in joints, as well as for modifying material interfacial properties. Model studies have revealed efficient lubricity by single-component lipid bilayers; synovial joints, however (e.g. hips and knees), comprise over a hundred different lipids, raising the question of whether this is natural redundancy or whether it confers any lubrication benefits. Here, we examine lubrication by progressively more complex mixtures of lipids representative of those in joints, using a surface forces balance at physiologically relevant salt concentrations and pressures. We find that different combinations of such lipids differ very significantly in the robustness of the bilayers to hemifusion under physiological loads (when lubrication breaks down), indicating a clear lubrication synergy afforded by multiple lipid types in the bilayers. Insight into the origins of this synergy is provided by detailed molecular dynamics simulations of potential profiles for the formation of stalks, the essential precursors of hemifusion, between bilayers of the different lipid mixtures used in the experiments. These reveal how bilayer hemifusion-and thus lubrication breakdown-depends on the detailed lipid bilayer composition, through the corresponding separation into domains that are better able to resist stalk formation. Our results shed light on the role of lipid-type proliferation in biolubrication synergy, point to improved treatment modalities for common joint diseases such as osteoarthritis, and indicate how lipid-based interfacial modification in a materials context may be optimized.

Therapeutic potential of resveratrol and autologous chondrocytes in male rat knee joint cartilage repair

Osteochondral defects (OCDs) in synovial joints are caused by trauma or inflammatory joint diseases, with no definitive treatment available. This study examined the effects of resveratrol and chondrocyte injections in a rat model of OCD. Twenty-four male Sprague-Dawley rats were divided into four groups: a control group, a resveratrol-only group (10 mg/kg), a chondrocyte-only group (1 × 105 cells), and a combined treatment group that received both treatments. After two months, the rats were euthanized, and their knee joints were analysed histologically and immunohistochemically. The results showed that the combined resveratrol and chondrocyte treatment significantly reduced fibrous tissue, increased cartilage tissue volume, improved cellular distribution, and enhanced the regularity of the articular surface. Collagen types I and II and proteoglycan levels were also elevated. These findings suggest that the combination of resveratrol and chondrocytes has a synergistic effect, promoting effective OCD repair in this rat model, offering potential for future therapeutic approaches.

KOC_Net: Impact of the Synthetic Minority Over-Sampling Technique with Deep Learning Models for Classification of Knee Osteoarthritis Using Kellgren–Lawrence X-Ray Grade

One of the most common diseases afflicting humans is knee osteoarthritis (KOA). KOA occurs when the knee joint cartilage breaks down, and knee bones start rubbing together. The diagnosis of KOA is a lengthy process, and missed diagnosis can have serious consequences. Therefore, the diagnosis of KOA at an initial stage is crucial which prevents the patients from Severe complications. KOA identification using deep learning (DL) algorithms has gained popularity during the past few years. By applying knee X-ray images and the Kellgren–Lawrence (KL) grading system, the objective of this study was to develop a DL model for detecting KOA. This study proposes a novel model based on CNN called knee osteoarthritis classification network (KOC_Net). The KOC_Net model contains 05 convolutional blocks, and each convolutional block has three components such as Convlotuioanl2D, ReLU, and MaxPooling 2D. The KOC_Net model is evaluated on two publicly available benchmark datasets which consist of X-ray images of KOA based on the KL grading system. Additionally, we applied contrast-limited adaptive histogram equalization (CLAHE) methods to enhance the contrast of the images and utilized SMOTE Tomek to deal with the problem of minority classes. For the diagnosis of KOA, the classification performance of the proposed KOC_Net model is compared with baseline deep networks, namely Dense Net-169, Vgg-19, Xception, and Inception-V3. The proposed KOC_Net was able to classify KOA into 5 distinct groups (including Moderate, Minimal, Severe, Doubtful, and Healthy), with an AUC of 96.71%, accuracy of 96.51%, recall of 91.95%, precision of 90.25%, and F1-Score of 96.70%. Dense Net-169, Vgg-19, Xception, and Inception-V3 have relative accuracy rates of 84.97%, 81.08%, 87.06%, and 83.62%. As demonstrated by the results, the KOC_Net model provides great assistance to orthopedics in making diagnoses of KOA.

Small heterodimer partner-interacting leucine zipper protein suppresses pain and cartilage destruction in an osteoarthritis model by modulating the AMPK/STAT3 signaling pathway

ObjectiveOsteoarthritis (OA) is a degenerative joint disease caused by the breakdown of joint cartilage and adjacent bone. Joint injury, being overweight, differences in leg length, high levels of joint stress, abnormal joint or limb development, and inherited factors have been implicated in the etiology of OA. In addition to physical damage to the joint, a role for inflammatory processes has been identified as well. Small heterodimer partner-interacting leucine zipper protein (SMILE) regulates transcription and many cellular functions. Among the proteins activated by SMILE is the peroxisome proliferator-activated receptor (PPAR) γ, which mediates the activities of CD4 + T helper cells, including Th1, Th2, and Th17, as well as Treg cells. PPAR-γ binds to STAT3 to inhibit its transcription, thereby suppressing the expression of the NF-κB pathway, and in turn, the expression of the inflammatory cytokines interferon (IFN), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, which are sub-signals of STAT3 and NF-κB.MethodsOA was induced in control C57BL/6 mice and in C57BL/6-derived SMILE-overexpressing transgenic (SMILE Tg) mice. The protein expression levels in the joint and spleen tissues were analyzed by immunohistochemistry and immunofluorescence images. In addition, flow cytometry was performed for detecting changes of the changes of immune cells.ResultsLess cartilage damage and significantly reduced levels of OA biomarkers (MMP13, TIMP3 and MCP-1) were observed in SMILE Tg mice. Immunohistochemistry performed to identify the signaling pathway involved in the link between SMILE expression and OA revealed decreased levels of IL-1β, IL-6, TNF-α, and phosphorylated AMPK in synovial tissues as well as a significant decrease in phosphorylated STAT3 in both cartilage and synovium. Changes in systemic immune cells were investigated via flow cytometry to analyze splenocytes isolated from control and SMILE Tg mice. SMILE Tg mice had elevated proportions of CD4 + IL-4 + cells (Th2) and CD4 + CD25 + Foxp3 + cells (Treg) and a notable decrease in CD4 + IL-17 + cells (Th17).ConclusionOur results show that overexpressed SMILE attenuates the symptoms of OA, by increasing AMPK signaling and decreasing STAT3, thus reducing the levels of inflammatory immune cells.

Morphometric evaluation of the proximal tibiofibular joint among patients with knee joint pain: A pilot study and literature review

Objectives: The proximal tibiofibular joint (PTFJ) serves as a crucial stabilizing component of the entire knee joint complex. Morphometric analysis of the PTFJ can lead to clinically significant conclusions for orthopedic specialists and physiotherapists. The aim of the study was to assess the values of the inclination angle of the PTFJ in the sagittal and coronal planes using magnetic resonance imaging in patients with knee pain. Material and Methods: Measurements of the inclination angle were conducted on 48 patients divided into three groups: Those with damaged medial meniscus (M), those with knee joint cartilage damage (Ca), and the control group (C), in which no deviations from normality were observed in the analyzed imaging study. Results: The mean values of the tibiofibular joint inclination angle in the frontal plane were as follows: (C) 16.927° ± 1.778; (Ca) 16.822° ± 2.537; (M) 14.958° ± 1.760. In the sagittal plane, the corresponding values were: (C) 38.155° ± 1.524; (Ca) 39.392° ± 1.927; (M) 37.471° ± 1.165. Although the mean tibiofibular joint inclination angle was lowest in the group with medial meniscus injury when compared to the control group, these differences did not reach statistical significance. Conclusion: Measuring and observing the variety of PTFJ inclination angles among patients are conducive to better understanding its influence on knee pain. The differences in the PTFJ inclination angle between groups in our pilot study were not statistically significant. Consequently, the study necessitates replication within a substantial population cohort.

The efficacy of ultrasonography-guided oxygen-ozone therapy versus corticosteroids in patients with knee osteoarthritis: A multicenter randomized controlled trial.

Osteoarthritis (OA) is a widely-known disease distinguished by the breakdown of joint cartilage, leading to pain and morning stiffness. In this context, the role of corticosteroids is well known, but there is still a gap of knowledge on the duty of oxygen-ozone therapy (O2-O3). To evaluate for effectiveness of ultrasound-guided O2-O3 injections compared with corticosteroid injections among patients diagnosed with knee OA. This randomized controlled clinical trial was conducted on participants with knee OA who were randomly sorted into two groups: group A, undergoing corticosteroid group (n= 47) and group B, undergoing O2-O3 (n= 49) were injected within the knee joint under ultrasound guidance. The primary outcome measure was the change in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score between baseline and 12-weeks post-injection. Secondary outcome measures included visual analog scale scores, joint effusion and a knee flexion ROM. Assessments were recorded at baseline and 4-weeks and 12-weeks post-injection. For the examination of intra- and inter-group variations at various time points, a repeated-measure analysis of variance (two-way ANOVA) was employed. Ninety-six participants completed this study. Based on repeated measurement analysis of variance, a significant effect of time was found for all outcome measures in both groups. Both groups showed clinically significant improvements in knee pain, quality of life and, function. Baseline, 4-week post-injection and 12-week post-injection WOMAC scores (mean ± standard deviation) were 72.54 ± 18.89, 45,95 ± 13.30 and 37.10 ± 19.87 (p= 0.00, p= 0.00, p= 0.00; respectively) in the corticosteroid group, respectively and 68.23 ± 20.18, 42.99 ± 18.67, and 33.43 ± 18.24 (p= 0.00, p= 0.00, p= 0.00; respectively) in the ozone group, respectively. However, no significant group × time interaction was determined regarding all outcome measures. The study demonstrates the efficacy of O2-O3 compared to steroid injections regarding functioning and pain relief among patients with diagnosed knee OA.

Salmon Nasal Cartilage-Derived Proteoglycans Alleviate Monosodium Iodoacetate-Induced Osteoarthritis in Rats.

Osteoarthritis is a chronic inflammatory condition characterized by the degeneration of joint cartilage and underlying bone, resulting in pain, swelling, and reduced mobility. This study evaluates the efficacy of salmon nasal cartilage-derived proteoglycans in mitigating osteoarthritis symptoms and investigates the underlying molecular mechanisms. This study employed a rat model of osteoarthritis induced by monosodium iodoacetate (MIA) injection. The rats were orally administered salmon nasal cartilage-derived proteoglycans or ibuprofen. Key aspects of osteoarthritis pathology, including impaired exercise ability, inflammation, extracellular matrix degradation, and chondrocyte apoptosis, were assessed using histological analysis, micro-CT, treadmill testing, serum assays, and mRNA/protein expression studies. The MIA injection caused significant cartilage damage, reduced bone mineral density, and impaired exercise ability. Additionally, it elevated serum levels of prostaglandin E2 and nitric oxide, increased the mRNA and protein levels of inflammation-related factors, and activated apoptosis signaling pathways in cartilage. Treatment with salmon nasal cartilage-derived proteoglycans significantly improved cartilage morphology and mineralization, reduced inflammation, and inhibited apoptosis signaling pathways, with effects comparable to those observed with ibuprofen treatment. These findings highlight the potential of salmon nasal cartilage-derived proteoglycans as a therapeutic agent for managing osteoarthritis by effectively reducing inflammation, preventing cartilage degradation, and inhibiting chondrocyte apoptosis.

Autologous chondrocyte implantation, matrix-induced autologous chondrocyte implantation, osteochondral autograft transplantation and osteochondral allograft improve knee function and pain with considerations for patient and cartilage defects characteristics: A systematic review and meta-analysis.

Previous studies have reported on the outcomes of autologous chondrocyte implantation (ACI) versus matrix-induced ACI (MACI) and microfracture. Specific clinical outcomes of ACI, MACI, osteochondral autograft transplantation (OAT) and osteochondral allograft (OCA) have not been well studied. The purpose of this systematic review and meta-analysis was to analyze the outcomes of these regenerative surgical techniques with an emphasis on comparing their effectiveness using the International Knee Documentation Committee (IKDC) subjective score, the Lysholm Knee Scoring Scale, the Tegner Activity Scale and the Visual Analogue Scale (VAS) score for the surgical treatment of tibiofemoral joint cartilage defects. An electronic search of MEDLINE, Embase and Cochrane Library was performed to identify studies that reported clinical outcomes for ACI, MACI, OAT and OCA procedures. The literature review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and only studies involving cartilage defects in the tibiofemoral joint were included. Outcomes were measured with the IKDC evaluation, Lysholm Knee Scoring Scale, Tegner Activity Scale and the VAS. Outcomes were compared to the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS). The methodological quality of the included studies was analyzed by the Methodological Index for Nonrandomized Studies and the Jadad scale. Forty-seven studies were included representing a total of 1993 patients with a mean follow-up time of 57.2 ± 40.3 months (range: 4.0-160.0 months). The location of cartilage defects was reported in 46 studies, with a total of 1922 cartilage defects. There were 1277 medial femoral condyle cartilage defects, 488 lateral femoral condyle cartilage defects, 139 unspecified femoral condyle cartilage defects and 18 tibial plateau cartilage defects. All four procedures reported significant improvements in the Lysholm, IKDC, Tegner and VAS scores with no significant differences between them. The OAT technique surpassed the PASS threshold for the IKDC score while all four techniques surpassed the PASS threshold for Tegner and Lysholm scores. Additionally, all procedures met the MCID for each clinical outcome. This systematic review and meta-analysis indicate that ACI, MACI, OAT and OCA all result in significant improvements in knee function and pain for cartilage defects of the tibiofemoral joint. When selecting a procedure, patient and cartilage defect characteristics should be assessed to determine the best technique for each individual patient. Systematic review and meta-analysis. Level III.

Controlled Stimulus-Responsive Delivery Systems for Osteoarthritis Treatment.

Osteoarthritis (OA), a common and disabling degenerative joint disease, affects millions of people worldwide and imposes a considerable burden on patients and society due to its high prevalence and economic costs. The pathogenesis of OA is closely related to the progressive degradation of articular cartilage and the accompany inflammation; however, articular cartilage itself cannot heal and modulate the inflammation due to the lack of nerves, blood vessels, and lymph-vessels. Therefore, reliable and effective methods to treat OA remain highly desired. Local administration of drugs or bioactive materials by intra-articular injection of the delivery system represents a promising approach to treat OA, especially considering the prolonged joint retention, cartilage or chondrocytes targeting, and stimuli-responsive release to achieve precision OA therapy. This article summarizes and discusses the advances in the currently used delivery systems (nanoparticle, hydrogel, liposome, and microsphere) and then focuses on their applications in OA treatment from the perspective of endogenous stimulus (redox reactions, pH, enzymes, and temperature) and exogenous stimulus (near-infrared, magnetic, and ultrasound)-responsive release. Finally, the challenges and potential future directions for the development of nano-delivery systems are summarized.

Lateral Meniscus Allograft Transplant With Capsulodesis and an Osteochondral Allograft to the Lateral Femoral Condyle

Background: Anterior cruciate ligament (ACL) injuries frequently present with lateral meniscal injuries, and when irreparable, this may lead to meniscectomy, increasing the risk for osteoarthritis. Lateral meniscal allograft transplant (LMAT) can restore knee function and proper contact pressures. When combined with osteochondral allograft (OCA) for chondral defects, results are highly positive. Indications: LMAT is indicated in relatively young patients (<50 years of age) with a symptomatic, meniscus-deficient knee that has failed conservative treatment. The knee must be stable, without articular cartilage damage that cannot be repaired, and patients should be able to adhere to postoperative rehabilitation and future care. Indications for OCA include young, active patients with posttraumatic osteochondral defects, osteonecrosis, osteochondritis dissecans, large focal defects, previous cartilage repair failure, or patellofemoral joint cartilage lesions. Technique Description: After a diagnostic arthroscopy is performed and concomitant injuries are ruled out, the lateral meniscal tissue is debrided to a 1- to 2-mm rim for the recipient site preparation. Tibial sockets for root fixation are created using tibial guides and passing sutures are placed. A capsulodesis is performed to reduce meniscal extrusion by securing the lateral capsule through a transtibial tunnel to the anteromedial tibial cortex with high-strength sutures. A meniscal allograft, prepared with bone plugs, is introduced through an enlarged anterolateral portal. After it is accurately positioned, it is stabilized using Fast-Fix Flex devices and circumferential sutures. The bone plug sutures are then fixed through the tibial tunnels to the anteromedial tibial cortex with a button. The large cartilage defect is addressed with an OCA transplant, involving defect measurement, careful reaming, and press-fit insertion of a donor plug, ensuring congruent articulation. Results: Patients can expect improved clinical outcomes and high patient satisfaction with LMAT and concomitant OCA. The use of bone plugs minimizes soft tissue dissection while achieving solid osseous fixation. Discussion/Conclusions: LMAT with OCA leads to restored contact pressures to near-physiological levels, a high patient satisfaction of over 85%, and mean allograft survival of 16 years. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Mechanism of Astragali Radix in treatment of knee osteoarthritis based on GLP-1/GLP-1R axis

This study aims to observe the effects of different doses of Astragali Radix on the expression of glucagon(GLP-1) in se-rum and glucagon receptor(GLP-1R) in cartilage tissue in rats with knee osteoarthritis(KOA), explore the effect of Astragali Radix on the inflammation and apoptosis of KOA by regulating GLP-1/GLP-1R signaling axis, and investigate the mechanism of its action in alleviating KOA. Forty-eight male SD rats were randomly divided into six groups: blank group, model group, low-, medium-, and high-dose Astragali Radix groups(3.125, 6.25, and 12.5 g·kg~(-1)), and glucosamine sulfate group(0.1 g·kg~(-1)). Except for the blank group, rats in other groups were injected with sodium iodoacetate(MIA) into the knee joint to establish KOA models. After successful modeling, the rats were continuously treated for five weeks. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of GLP-1, tumor necrosis factor-alpha(TNF-α), and interleukin-1β(IL-1β) in rat serum. Pathological examination was utilized to observe the pathological changes in knee joint cartilage. The mRNA levels of TNF-α and MMP13 in knee joint cartilage were detected by qRT-PCR, and the protein expression levels of GLP-1R, MMP13, and caspase-8 in knee joint cartilage were detected by Western blot. The expression of GLP-1R and MMP13 in the knee joint was detected by immunohistochemistry. Tunel staining was used to observe the apoptosis of chondrocytes in the knee joint. The above experimental results showed that Astragali Radix may raise the serum levels of GLP-1, reduce serum levels of TNF-α and IL-1, and decrease the relative mRNA expression of TNF-α and MMP13 through the GLP-1/GLP-1R axis. It thus activated GLP-1R, reduced the protein expression of MMP13 and caspase-8 in cartilage, and regulated their related signaling pathways to improve inflammation and apoptosis, so as to protect cartilage and improve KOA.

High levels of glycated haemoglobin (HbA1c) are associated with lower knee joint cartilage quality and higher knee joint symptoms in healthy individuals.

In an asymptomatic population, we investigated the relationships between glycated haemoglobin (HbA1c) and cartilage T2 relaxation time at the knee joint level. Fourteen and 17 participants with high and normal levels of HbA1c were recruited, respectively. A blood sample was used to determine the HbA1c level. T2 relaxation time (T2) of the superficial and deep parts of the femoral cartilage in the anterior, central, and posterior topographical sites was calculated using magnetic resonance (1.5T) images. Each participant completed a knee injury and osteoarthritis outcome score questionnaire (KOOS) and a series of biomechanical analyses while running at their self-selected speed. The group with a high level of HbA1c had a lower score of KOOS symptoms than the other group (P < 0.05). HbA1c was found to be negatively related to the KOOS symptoms score. The group with a high level of HbA1c had low T2 values in all of the investigated topographical sites of the knee femoral cartilage (P < 0.05 in all cases). T2 was negatively correlated with HbA1c levels in all investigated knee femoral cartilage regions. Our data suggest that the subjects with high levels of HbA1c were those with low knee joint symptoms and lower values of T2. These results indicate that HbA1c could be correlated with cartilage deterioration due to its ability to dehydrate collagen fibre, possibly acting as a risk factor for the development of osteoarthritis.

Connecting the dots: NETosis and the periodontitis-rheumatoid arthritis nexus.

Periodontitis (PD) is characterized by the host's inflammatory responses to microbial dental biofilm dysbiosis, potentially resulting in tooth loss if left untreated. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease leading to synovial inflammation and destruction of joint cartilage and bone. The suggested association between PD and RA is based on the potential of chronic inflammation present in periodontitis, which could induce alterations in proteins through post-translational modifications, leading to the formation of citrullinated and carbamylated protein antigens. Antibodies directed against these antigens can serve as biomarkers for the underlying immunological processes in RA. Recent studies have also focused on bacterial proteolytic enzymes released from PD-associated bacteria, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, which are also sources of these antibodies. Chronic inflammation in PD causes increased levels of inflammatory cytokines (interferon-α, interleukins-6 and 8, tumor necrosis factor-α) and neutrophil extracellular traps (NETs). The oral microbiota in PD is also associated with the release of NETs (a process known as NETosis). Elevated NET levels are a source of citrullinated and carbamylated proteins which highlights their role in an individual's risk of developing RA (pre-RA individuals) and the progression of chronic RA. This narrative review describes periodontitis and the dysbiotic subgingival microbiota and its role in NETosis as risk factors for inducing early RA and the prospects of identifying pre-RA individuals and seronegative RA patients with these risk factors.

APPLICATION OF GENETICALLY MODIFIED INDUCED PLURIPOTENT STEM CELL LINES IN ARTICULAR CARTILAGE TISSUE ENGINEERING

The restoration of hyaline cartilage poses a complex clinical and scientific challenge due to its low regenerative potential. Joint cartilage injuries contribute to the development of osteoarthritis and, as a consequence, loss of joint function, and subsequent disability. Surgical approaches such as mosaic chondroplasty and microfracture are applicable only to relatively small defects and are unsuitable for patients with degenerative cartilage conditions. Developing of cell therapies using chondrocytes differentiated from induced pluripotent stem cells (iPSCs) is a promising direction for joint cartilage tissue reconstruction. iPSCs have high proliferative activity, allowing the generation of autologous cells in the amount required to restore an individual’s articular defect. The CRISPR-Cas genome editing technology, based on the bacterial adaptive immune system, enables genetic modification of iPSCs to produce progenitor cells with specific characteristics and properties. This review contains scientific studies of highly specialized focus on combining iPSC and CRISPR-Cas technologies for research in cartilage regenerative medicine. We have compiled articles over the past twelve years, since CRISPR-Cas became available to the world community. Currently, for the field of regenerative medicine of articular cartilage CRISPR-Cas is used to increase the effectiveness of chondrogenic differentiation of iPSCs and to obtain a chondroprogenitor population with a high homogeneity. Additionally, deletion of a sequence of pro-inflammatory cytokine receptors is conducted to produce inflammation-resistant tissue. Finally, knockout of major histocompatibility complex components allows the creation of hypoimmunogenic chondrocytes. These approaches contribute to the development of personalized medicine and may, in the long term, lead to improved quality of life for the global population.