Destruction Of Articular Cartilage Research Articles

COMPARATION OF KINESITHERAPY AND POWERPLATE IN PATIENTS WITH CERVICOARTHROSIS

Osteoarthritis is a chronic disease of the musculoskeletal system, in which degeneration of the affected tissues is observed. Modern living conditions and immobility create favorable conditions for the spread of the disease. The cervical region of the spine is subjected to significant dynamic and static loads, which often leads to pain and limited mobility. Diagnosing cervical arthrosis at an early stage opens up opportunities for effective and timely complex treatment. Such treatment includes not only medicinal approaches, but also various physical therapies, balneotherapy, as well as massage and kinesitherapy. Improving and maintaining the functional status of patients with cervical arthrosis is essential for their quality of life. This disease is characterized by destruction of articular cartilage, in which the formation of new tissue at the edges of bones and tendons is observed. It has a progressive course and affects a significant part of the population. These changes are part of the aging process of the body and the musculoskeletal system. The patented technology of Power Plate is designed to trigger the body’s innate reflexive reaction to precise vibrations, stimulating muscles in a consistent and regulated fashion, thereby expediting the benefits of training. Power Plate’s efficacy has been substantiated through numerous medical and scientific investigations, alongside practical application in clinical recovery and wellness establishments, sports enhancement hubs, and widespread adoption by a multitude of professional and collegiate sports organizations in the United States, as well as numerous others globally. Vibration is defined as an oscillatory motion involving mechanical forces. Its intensity is influenced by biomechanical parameters such as amplitude, frequency, and the scale of the oscillations. Specifically, amplitude refers to the peak-to-peak displacement measured in millimeters, frequency relates to the rate at which oscillation cycles repeat and is measured in Hertz (Hz), and acceleration reflects the scale of the vibrations. This study aims to compare the efficacy of two therapeutic interventions, kinesitherapy (analytical exercises) and power plate, in enhancing muscle strength and improving cervical range of motion. Eighteen patients were divided into experimental (n=10) and control (n=8) groups. The control group received physical medicine and kinesitherapy, while the experimental group underwent physical medicine and power plate therapy, both for 21 days. Clinical assessments were conducted pre- and post-therapy. Results indicated symptom improvement in both groups, with better outcomes observed in the control group. Furthermore, the control group exhibited more significant improvements in range of motion compared to the experimental group. Kinesitherapy demonstrated greater efficacy than power plate therapy, likely due to its targeted muscle exercises and isotonic/ isometric contraction combination, as opposed to the rapid and numerous contractions induced by the power plate. These findings highlight the importance of tailored therapeutic approaches in enhancing muscle strength and cervical spine mobility.

Effect of weight loss and exercise on joint pain in patients with osteoarthritis and obesity

Osteoarthritis (OA), the most common joint disease, coexists with obesity in most of the world’s population. According to the forecast of the World Health Organization, the number of patients with these diseases is expected to increase, which represents a serious medical and social problem due to increased disability, the need for surgical treatment, an increase in comorbid diseases, treatment complications and mortality in this group of patients. OA and obesity have common pathogenetic mechanisms, and the development of one disease increases the risk of developing the other, which can become the beginning of a vicious circle. In recent years, obesity is considered not only as a biomechanical factor (excessive load on the joint, destruction of articular cartilage), but also as a cause of metabolic syndrome and systemic inflammatory effects. Inflammatory cytokines, especially IL-1β and TNF-α, drive catabolic pathways and promote the progression of OA. There is compelling evidence that weight loss reduces pain and joint inflammation and improves prognosis in patients with OA. The review presents data on the prevalence of OA and obesity, the role of immune disorders in these diseases, and indicates methods of pharmacological and non-pharmacological treatment of OA. General principles and specific updated recommendations of the European League Against Rheumatism for non-drug treatment of OA of the hip and knee joints are outlined, and recommendations for weight loss through dietary interventions and exercise are formulated.

The Miao medicine Sidaxue alleviates rheumatoid arthritis in rats possibly by downregulating matrix metalloproteinases

To explore the inhibitory effect of Sidaxue, a traditional Miao herbal medicine formula, on articular bone and cartilage destruction and synovial neovascularization in rats with collagen-induced arthritis (CIA). In a SD rat model of CIA, we tested the effects of daily gavage of Sidaxue at low, moderate and high doses (10, 20, and 40 g/kg, respectively) for 21 days, with Tripterygium glycosides (GTW) as the positive control, on swelling in the hind limb plantar regions by arthritis index scoring. Pathologies in joint synovial membrane of the rats were observed with HE staining, and serum TNF-α and IL-1β levels were detected with ELISA. The expressions of NF-κB p65, matrix metalloproteinase 1 (MMP1), MMP2 and MMP9 at the mRNA and protein levels in the synovial tissues were detected using real-time PCR and Western blotting. Network pharmacology analysis was conducted to identify the important target proteins in the pathways correlated with the therapeutic effects of topical Sidaxue treatment for RA, and the core target proteins were screened by topological analysis. Treatment with GTW and Sidaxue at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, improved cartilage and bone damage and reduced neovascularization in CIA rats (P<0.05), and the effects of Sidaxue showed a dose dependence. Both GTW and Sidaxue treatments significantly lowered TNF-α, IL-1β, NF-κB p65, MMP1, MMP2, and MMP9 mRNA and protein expressions in the synovial tissues of CIA rats (P<0.05). Network pharmacological analysis identified MMPs as the core proteins associated with topical Sidaxue treatment of RA. Sidaxue alleviates articular bone and cartilage damages and reduces synovial neovascularization in CIA rats possibly by downregulating MMPs via the TNF-α/IL-1β/NF-κB-MMP1, 2, 9 signaling pathway, and MMPs probably plays a key role in mediating the effect of Sidaxue though the therapeutic pathways other than oral administration.

Carrier-free poly(glycyrrhetinic acid)-facilitated celastrol-loaded nanoparticle for high-efficiency low-toxicity treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a complex autoimmune disease associated with synovial inflammation and articular cartilage destruction. Currently, high-efficiency low-toxicity management of this intractable disease is highly urgent. Here, a drug-backboned polymer, polyglycyrrhetinic acid (PGA), was synthesized through the condensation of GA, a principal anti-inflammatory component of Glycyrrhiza glabra. PGA was then used as a therapeutic polyprodrug carrier to fabricate carrier-free PGA@Cel nanoparticles (NPs) for treating rheumatoid arthritis. The as-prepared NPs exhibited a uniformly spherical morphology with an average particle size of approximately 180 nm and a celastrol (Cel) loading capacity of around 4.5 %. Upon intravenous injection, the NPs demonstrated prolonged blood circulation, efficient accumulation at inflammatory joints through extravasation via leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS) effect. The present study demonstrated enhanced anti-inflammatory and rheumatic decay efficiency in rat models of antigen-induced arthritis, while simultaneously minimizing off-target toxicity. Overall, our results elucidate that this carrier-free drug-backboned nanopolydrug platform provides a promising strategy for RA therapy.

TRPM7 facilitates fibroblast-like synoviocyte proliferation, metastasis and inflammation through increasing IL-6 stability via the PKCα-HuR axis in rheumatoid arthritis

Transient receptor potential melastatin 7 (TRPM7) is a cation channel that plays a role in the progression of rheumatoid arthritis (RA), yet its involvement in synovial hyperplasia and inflammation has not been determined. We previously reported that TRPM7 affects the destruction of articular cartilage in RA. Herein, we further confirmed the involvement of TRPM7 in fibroblast-like synoviocyte (FLS) proliferation, metastasis and inflammation. We observed increased TRPM7 expression in FLSs derived from human RA patients. Pharmacological inhibition of TRPM7 protected primary RA-FLSs from proliferation, metastasis and inflammation. Furthermore, we found that TRPM7 contributes to RA-FLS proliferation, metastasis and inflammation by increasing the intracellular Ca2+ concentration. Mechanistically, the PKCα-HuR axis was demonstrated to respond to Ca2+ influx, leading to TRPM7-mediated RA-FLS proliferation, metastasis and inflammation. Moreover, HuR was shown to bind to IL-6 mRNA after nuclear translocation, which could be weakened by TRPM7 channel inhibition. Additionally, adeno-associated virus 9-mediated TRPM7 silencing is highly effective at alleviating synovial hyperplasia and inflammation in adjuvant-induced arthritis rats. In conclusion, our findings unveil a novel regulatory mechanism involved in the pathogenesis of RA and suggest that targeting TRPM7 might be a potential strategy for the prevention and treatment of RA.

Reaming for Tibiotalocalcaneal Nailing Removes Only 10% of the Ankle and Subtalar Joints.

Tibiotalocalcaneal (TTC) nailing in the setting of acute ankle trauma has become increasingly popular. No consensus exists as to whether formal joint preparation is necessary, although there is some concern that residual motion at unprepared joints may lead to implant loosening and/or breakage. The objective of this study was to quantify the proportion of tibiotalar and subtalar articular surface destruction that occurs during reaming for TTC nail fixation. Twelve cadaver lower extremities were procured. The specimens were pinned into neutral ankle and hindfoot alignment. A guidewire was inserted under fluoroscopy, followed by a 12-mm opening reamer. The specimens were then dissected, exposing the tibial plafond, talar dome, posterior facet of the talus, and posterior facet of the calcaneus. Images of each joint were obtained, and ImageJ software was used to calculate the total joint surface area and the area of articular destruction. The mean proportion of articular cartilage destruction was 9.3%, 10.3%, 8.9%, and 10.3% for the tibial plafond, talar dome, posterior facets of the talus, and posterior facets of the calcaneus, respectively. No joint destruction was observed in the middle facets of the subtalar joint. Reaming for TTC nail placement violates approximately 10% of each articular surface of the tibiotalar and subtalar joints. Retention of 90% of the articular surface may allow for residual motion at the joints and therefore potentially substantial stress on the implant. Formal joint preparation for the purposes of achieving fusion during TTC nail placement may be beneficial to prevent implant loosening or breakage.

TMF inhibits extracellular matrix degradation by regulating the C/EBPβ/ADAMTS5 signaling pathway in osteoarthritis

Osteoarthritis (OA) is a chronic joint disease, characterized by degenerative destruction of articular cartilage. Chondrocytes, the unique cell type in cartilage, mediate the metabolism of extracellular matrix (ECM), which is mainly constituted by aggrecan and type II collagen. A disintegrin and metalloproteinase with thrombospondin 5 (ADAMTS5) is an aggrecanase responsible for the degradation of aggrecan in OA cartilage. CCAAT/enhancer binding protein β (C/EBPβ), a transcription factor in the C/EBP family, has been reported to mediate the expression of ADAMTS5. Our previous study showed that 5,7,3’,4’-tetramethoxyflavone (TMF) could activate the Sirt1/FOXO3a signaling in OA chondrocytes. However, whether TMF protected against ECM degradation by down-regulating C/EBPβ expression was unknown. In this study, we found that aggrecan expression was down-regulated, and ADAMTS5 expression was up-regulated. Knockdown of C/EBPβ could up-regulate aggrecan expression and down-regulate ADAMTS5 expression in IL-1β-treated C28/I2 cells. TMF could compromise the effects of C/EBPβ on OA chondrocytes by activating the Sirt1/FOXO3a signaling. Conclusively, TMF exhibited protective activity against ECM degradation by mediating the Sirt1/FOXO3a/C/EBPβ pathway in OA chondrocytes.

Effects of alendronate on cartilage lesions and micro-architecture deterioration of subchondral bone in patellofemoral osteoarthritic ovariectomized rats with patella-baja

BackgroundPatellofemoral osteoarthritis (PFJOA) is a subtype of knee OA, which is one of the main causes of anterior knee pain. The current study found an increased prevalence of OA in postmenopausal women, called postmenopausal OA. Therefore, we designed the ovariectomized rat model of patella baja-induced PFJOA. Alendronate (ALN) inhibits osteoclast-mediated bone loss, and has been reported the favorable result of a potential intervention option of OA treatment. However, the potential effects of ALN treatment on PFJOA in the ovariectomized rat model are unknown and need further investigation prior to exploration in the clinical research setting. In this study, the effects of ALN on articular cartilage degradation and subchondral bone microstructure were assessed in the ovariectomized PFJOA rat model for 10 weeks.MethodsPatella baja and estrogen withdrawal were induced by patellar ligament shortening (PLS) and bilateral ovariectmomy surgeries in 3-month-old female Sprague–Dawley rats, respectively. Rats were randomly divided into five groups (n = 8): Sham + V; OVX + V, Sham + PLS + V, OVX + PLS + V, OVX + PLS + ALN (ALN: 70 μg/kg/week). Radiography was performed to evaluate patellar height ratios, and the progression of PFJOA was assessed by macroscopic and microscopic analyses, immunohistochemistry and micro-computed tomography (micro-CT).ResultsOur results found that the patella baja model prepared by PLS can successfully cause degeneration of articular cartilage and subchondral bone, resulting in changes of PFJOA. OVX caused a decrease in estrogen levels in rats, which aggravated the joint degeneration caused by PFJOA. Early application of ALN can delay the degenerative changes of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent, improve and maintain the micrometabolism and structural changes of cartilage and subchondral bone.ConclusionThe early application of ALN can delay the destruction of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent.

Vigeo attenuates cartilage and bone destruction in a collagen‑induced arthritis mouse model by reducing production of pro‑inflammatory cytokines.

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease characterized by articular cartilage destruction, bone destruction and synovial hyperplasia. It has been suggested that Vigeo, a mixture of Eleutherococcus senticosus, Achyranthes japonica and Atractylodes japonica fermented with Korean nuruk, has an anti-osteoporotic effect in a mouse model of inflammation-mediated bone loss. The present study evaluated the therapeutic effects of Vigeo in RA using a collagen-induced arthritis (CIA) mouse model. DBA/1J mice were immunized with bovine type II collagen on days 0 and 21 and Vigeo was administered daily for 20 days beginning the day after the second type II collagen injection. The mice were sacrificed on day 42 and the joint tissues were anatomically separated and subjected to micro computed tomography and histological analyses. In addition, the serum levels of TNF-α, IL-6 and IL-1β were determined by enzyme-linked immunosorbent assays. CIA in DBA/1J mice caused symptoms of RA, such as joint inflammation, cartilage destruction and bone erosion. Treatment of CIA mice with Vigeo markedly decreased the symptoms and cartilage pathology. In addition, radiological and histological analyses showed that Vigeo attenuated bone and cartilage destruction. The serum TNF-α, IL-6 and IL-1β levels following oral Vigeo administration were also reduced when compared with those in CIA mice. The present study revealed that Vigeo suppressed arthritis symptoms in a CIA-RA mouse model, including bone loss and serum levels of TNF-α, IL-6 and IL-1β.

Protective effects of ectoine on articular chondrocytes and cartilage in rats for treating osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative disease that primarily includes articular cartilage destruction and inflammatory reactions, and effective treatments for this disease are still lacking. The present study aimed to explore the protective effects of ectoine, a compatible solute found in nature, on chondrocytes in rats and its possible application in OA treatment. In the in vitro studies, the morphology of the chondrocytes after trypsin digestion for 2 min and the viability of the chondrocytes at 50°C were observed after ectoine treatment. The reactive oxygen species (ROS) levels in chondrocytes pretreated with ectoine and post-stimulated with H2O2 were detected using an ROS assay. Chondrocytes were pretreated with ectoine before IL-1β stimulation. RT‒qPCR was used to measure the mRNA levels of cyclooxygenase-2 (COX-2), metallomatrix proteinase-3, -9 (MMP-3, -9), and collagen type II alpha 1 (Col2A1). In addition, immunofluorescence was used to assess the expression of type II collagen. The in vivo effect of ectoine was evaluated in a rat OA model induced by the modified Hulth method. The findings revealed that ectoine significantly increased the trypsin tolerance of chondrocytes, maintained the viability of the chondrocytes at 50°C, and improved their resistance to oxidation. Compared with IL-1β treatment alone, ectoine pretreatment significantly reduced COX-2, MMP-3, and MMP-9 expression and maintained type II collagen synthesis in chondrocytes. In vivo, the cartilage of ectoine-treated rats exhibited less degeneration and lower Osteoarthritis Research Society International (OARSI) scores. The results of this study suggest that ectoine exerts protective effects on chondrocytes and cartilage and can, therefore, be used as a potential therapeutic agent in the treatment of OA.

Lubricating MXenzyme-based hybrid hydrogel reverses oxidative damage to alleviate osteoarthritis

Osteoarthritis (OA) is a lubrication-deficient joint disease accompanied by persistent inflammation and progressive destruction of articular cartilage. Although the exact pathogenesis is still unclear, oxidative stress-induced metabolic imbalance and chondrocyte death are thought to take on a crucial role. Here, we present an injectable hydrogel drug delivery system based on V2C MXenzyme NS, metformin and DexMA to alleviate the progression of OA. Due to the advantageous properties of MXenzyme, MXenzyme hybrid hydrogel not only enabled the intelligent release of metformin in response to pH, but also formed a lubricant layer on the hydrogel surface for stable boundary lubrication. Moreover, MXenzyme hybrid hydrogel could scavenge excess reactive oxygen species (ROS) in chondrocytes, including H2O2 and O2−, to alleviate oxidative stress and protect mitochondrial function. Most notably, MXenzyme Hybrid Hydrogel also maintained cartilage extracellular matrix metabolic homeostasis and inhibited chondrocyte pyroptosis through activating Nrf2-ARE signaling, thereby protected cartilage tissues and mitigated the progression of OA. Collectively, the MXenzyme hybrid hydrogel is a promising nano-delivery system for the treatment of OA.

Mesenchymal stem cell-derived exosomes as a promising cell-free therapy for knee osteoarthritis.

Osteoarthritis (OA), as a degenerative disease, leads to high socioeconomic burdens and disability rates. The knee joint is typically the most affected and is characterized by progressive destruction of articular cartilage, subchondral bone remodeling, osteophyte formation and synovial inflammation. The current management of OA mainly focuses on symptomatic relief and does not help to slow down the advancement of disease. Recently, mesenchymal stem cells (MSCs) and their exosomes have garnered significant attention in regenerative therapy and tissue engineering areas. Preclinical studies have demonstrated that MSC-derived exosomes (MSC-Exos), as bioactive factor carriers, have promising results in cell-free therapy of OA. This study reviewed the application of various MSC-Exos for the OA treatment, along with exploring the potential underlying mechanisms. Moreover, current strategies and future perspectives for the utilization of engineered MSC-Exos, alongside their associated challenges, were also discussed.

Lubricating Microneedles System with Multistage Sustained Drug Delivery for the Treatment of Osteoarthritis.

Osteoarthritis (OA) is a typical joint degenerative disease that is prevalent worldwide and significantly affects the normal activities of patients. Traditional treatments using diclofenac (DCF) as an anti-inflammatory drug by oral administration and transdermal delivery have many inherent deficiencies. In this study, a lubricating microneedles (MNs) system for the treatment of osteoarthritis with multistage sustained drug delivery and great reduction in skin damage during MNs penetration is developed. The bilayer dissolvable MNs system, namely HA-DCF@PDMPC, is prepared by designating the composite material of hyaluronic acid (HA) and covalently conjugated drug compound (HA-DCF) as the MNs tips and then modifying the surface of MNs tips with a self-adhesive lubricating copolymer (PDMPC). The MNs system is designed to achieve sustained drug release of DCF via ester bond hydrolysis, physical diffusion from MNs tips, and breakthrough of lubrication coating. Additionally, skin damage is reduced due to the presence of the lubrication coating on the superficial surface. Therefore, the lubricating MNs with multistage sustained drug delivery show good compliance as a transdermal patch for OA treatment, which is validated from anti-inflammatory cell tests and therapeutic animal experiments, down-regulating the expression levels of pro-inflammatory factors and alleviating articular cartilage destruction.

Screening of the key response component groups and mechanism verification of Huangqi-Guizhi-Wuwu-Decoction in treating rheumatoid arthritis based on a novel computational pharmacological model

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the destruction of synovial tissue and articular cartilage. Huangqi-Guizhi-Wuwu-Decoction (HGWD), a formula of Traditional Chinese Medicine (TCM), has shown promising clinical efficacy in the treatment of RA. However, the synergistic effects of key response components group (KRCG) in the treatment of RA have not been well studied.MethodsThe components and potential targets of HGWD were extracted from published databases. A novel node influence calculation model that considers both the node control force and node bridging force was designed to construct the core response space (CRS) and obtain key effector proteins. An increasing coverage coefficient (ICC) model was employed to select the KRCG. The effectiveness and potential mechanism of action of KRCG were confirmed using CCK-8, qPCR, and western blotting.ResultsA total of 796 key effector proteins were identified in CRS. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses confirmed their effectiveness and reliability. In addition, 59 components were defined as KRCG, which contributed to 85.05% of the target coverage of effective proteins. Of these, 677 targets were considered key reaction proteins, and their enriched KEGG pathways accounted for 84.89% of the pathogenic genes and 87.94% of the target genes. Finally, four components (moupinamide, 6-Paradol, hydrocinnamic acid, and protocatechuic acid) were shown to inhibit the inflammatory response in RA by synergistically targeting the cAMP, PI3K-Akt, and HIF-1α pathways.ConclusionsWe have introduced a novel model that aims to optimize and analyze the mechanisms behind herbal formulas. The model revealed the KRCG of HGWD for the treatment of RA and proposed that KRCG inhibits the inflammatory response by synergistically targeting cAMP, PI3K-Akt, and HIF-1α pathways. Overall, the novel model is plausible and reliable, offering a valuable reference for the secondary development of herbal formulas.

Efficacy and safety of the modified Zhiwang decoction combined with methotrexate in early rheumatoid arthritis: study protocol for a randomised controlled trial

IntroductionRheumatoid arthritis (RA) is a progressive inflammatory autoimmune disease characterised by chronic systemic inflammation, which can cause swelling, stiffening and destruction of articular cartilage and bone. Early diagnosis and treatment...

Osteoarthritis in the Elderly Population: Preclinical Evidence of Nutrigenomic Activities of Flavonoids.

Osteoarthritis (OA) is a degenerative joint disease that is age-related and progressive. It causes the destruction of articular cartilage and underlying bone, often aggravated by inflammatory processes and oxidative stresses. This pathology impairs the quality of life of the elderly, causing pain, reduced mobility, and functional disabilities, especially in obese patients. Phytochemicals with anti-inflammatory and antioxidant activities may be used for long-term treatment of OA, either in combination with current anti-inflammatories and painkillers, or as an alternative to other products such as glucosamine and chondroitin, which improve cartilage structure and elasticity. The current systematic review provides a comprehensive understanding of the use of flavonoids. It highlights chondrocyte, cartilage, and subchondral bone activities, with a particular focus on their nutrigenomic effects. The molecular mechanisms of these molecules demonstrate how they can be used for the prevention and treatment of OA in the elderly population. However, clinical trials are still needed for effective use in clinical practice.

Comparison of the Effectiveness of Intra-articular Infiltration of Hyaluronic Acid and Corticosteroids in the Management of Knee Osteoarthritis: A Prospective Comparative Study.

Background Knee osteoarthritis (KOA) is a chronic and progressive disease of the knee joint characterized by articular cartilage destruction. It is the most common cause of knee disability and pain globally. Various treatments are used for the management of KOA; however, the role of intra-articular injections in KOA management in Pakistan remains understudied. Therefore, this study aims to evaluate the effectiveness of intra-articular injections of hyaluronic acid (HA) and corticosteroids in the management of KOA. Methodology This randomized, prospective, comparative study was conducted among 88 patients diagnosed with KOA in the outpatient department clinic of orthopedics in Benazir Bhutto Hospital, Rawalpindi, from January 2022 to January 2023. For patient enrolment, structured inclusion and exclusion criteria and a simple random sampling technique were used. Before data collection, ethical approval and informed consent were obtained. Data collection was done via a self-structured and interview-based proforma. Data analysis was performed through descriptive statistics and independent t-tests using SPSS version 25 (IBM Corp., Armonk, NY, USA). Results KOA was more prevalent in women (60, 68.18%) than men (28, 31.82%). The means for study variables such as age, Visual Analog Scale (VAS) score, and Western Ontario and McMaster Universities (WOMAC) score were 58.08 ± 7.89 years, 7.66 ± 1.8, and 71.86 ± 8.90, respectively. The incidences of right-sided and left-sided KOA were 57 (64.77%) and 31 (35.23%), respectively. Likewise, the frequency of grade II KOA was 55 (62.50%), while the frequency of grade III KOA was 33 (37.50%). Differences in the mean scores of both VAS and WOMAC between study groups were statistically significant at the second-week, sixth-week, and third-month follow-up visits. However, the mean scores of VAS and WOMAC were lower in group B than in group A at the second-week follow-up visit, whereas the scores were lower in group A compared to group B after the sixth week and third month of intra-articular injections. Conclusions Intra-articular injections of both HA and corticosteroids were adequately effective in the management of KOA-associated pain and functional restrictions; nevertheless, the benefits of corticosteroids were acute and short-term, whereas the outcomes of HA were gradual and long-term.

IgSF11 deficiency alleviates osteoarthritis in mice by suppressing early subchondral bone changes

Osteoarthritis (OA) is a degenerative joint disease. While it is classically characterized by articular cartilage destruction, OA affects all tissues in the joints and is thus also accompanied by local inflammation, subchondral bone changes, and persistent pain. However, our understanding of the underlying subchondral bone dynamics during OA progression is poor. Here, we demonstrate the contribution of immunoglobulin superfamily 11 (IgSF11) to OA subchondral bone remodeling by using a murine model. In particular, IgSF11 was quickly expressed by differentiating osteoclasts and upregulated in subchondral bone soon after destabilization-of-the-medial-meniscus (DMM)-induced OA. In mice, IgSF11 deficiency not only suppressed subchondral bone changes in OA but also blocked cartilage destruction. The IgSF11-expressing cells in OA subchondral bone were found to be involved in osteoclast maturation and bone resorption and colocalized with receptor-activator of nuclear-factor κ-B (RANK), the key osteoclast differentiation factor. Thus, our study shows that blocking early subchondral bone changes in OA can ameliorate articular cartilage destruction in OA.

Role of pathogenic and mentally pathogenic microflora, which are localized in the orotopharynx in the ethiopathogenesis of secondary osteoarthrosis

ABSTRACT. Much attention is paid to the problem of secondary osteoarthritis caused by various microorganisms and fungi of the genus S. albicans, associated with their significant growth and prevalence throughout the world among the population of various age groups, high temporary and permanent disability. At the same time, the problem of immunopathology in the pathogenesis of secondary osteoarthritis is being actively studied. The developed immunopathological process induced by pathogenic and opportunistic microflora in articular cartilage and synovial membrane is the main factor in the degenerative destruction of articular cartilage. Goal. to determine the role of pathogenic and opportunistic microflora localized in the oropharynx in the etiopathogenesis of secondary osteoarthritis. Research materials and methods. 65 patients aged from 19 to 45 years, who were undergoing inpatient treatment at Artz Klinic, Kharkiv, were examined for secondary osteoarthritis of the knee joint. The diagnosis was established according to the International Classification of Diseases of the 10th revision (ICD-10) - M18.1. Patients with a history of a high frequency of accompanying pathologies of the oropharynx were selected for the study: chronic tonsillitis - 48 (73.8%), tonsillitis - 32 (49.2%), pharyngitis - 34 (52.3%), sinusitis - 13 (20) %), otitis – 9 (13.8%) the etiology of which is determined by gram-positive and gram-negative microorganisms. All patients underwent microbiological examination of throat swabs, and 24 patients underwent microbiological examination of synovial fluid, which was taken for examination before intra-articular therapy. The obtained data were statistically processed by calculating the arithmetic mean and its error. The results. Presented modern ideas about secondary osteoarthritis caused by etiologically significant macroflora persisting in the oropharynx and as a result of organotropy due to the inclusion in its structure of mimicking antigens of articular cartilage play a leading role in the degradation of articular cartilage and articular bag, transferring the pathological process to an autoimmune basis. This approach makes it possible to develop early immunodiagnostics, prognosis of the disease, and immunocorrective therapy. Conclusions. Pathogenic and conditionally pathogenic microflora persisting in the oropharynx is characterized by organotropy (community of lipopolysaccharides and glycoproids), is identical to the cell-tissue structures of articular cartilage and synovial membrane in the causative agent and modulates the immune response through mimicking antigens.

H3K36 methyltransferase NSD1 protects against osteoarthritis through regulating chondrocyte differentiation and cartilage homeostasis.

Osteoarthritis (OA) is one of the most common joint diseases, there are no effective disease-modifying drugs, and the pathological mechanisms of OA need further investigation. Here, we show that H3K36 methylations were decreased in senescent chondrocytes and age-related osteoarthritic cartilage. Prrx1-Cre inducible H3.3K36M transgenic mice showed articular cartilage destruction and osteophyte formation. Conditional knockout Nsd1Prrx1-Cre mice, but not Nsd2Prrx1-Cre or Setd2Prrx1-Cre mice, replicated the phenotype of K36M/+; Prrx1-Cre mice. Immunostaining results showed decreased anabolic and increased catabolic activities in Nsd1Prrx1-Cre mice, along with decreased chondrogenic differentiation. Transcriptome and ChIP-seq data revealed that Osr2 was a key factor affected by Nsd1. Intra-articular delivery of Osr2 adenovirus effectively improved the homeostasis of articular cartilage in Nsd1Prrx1-Cre mice. In human osteoarthritic cartilages, both mRNA and protein levels of NSD1 and OSR2 were decreased. Our results indicate that NSD1-induced H3K36 methylations and OSR2 expression play important roles in articular cartilage homeostasis and OA. Targeting H3K36 methylation and OSR2 would be a novel strategy for OA treatment.