Progressive Cartilage Loss Research Articles

Injectable decellularized extracellular matrix hydrogel with cell-adaptable supramolecular network enhances cartilage regeneration by regulating inflammation and facilitating chondrogenesis

Osteoarthritis, characterized by progressive loss of cartilage, affects millions of people worldwide and clinically lacks effective treatments. Herein, we present an injectable, biodegradable supramolecular decellularized extracellular matrix (dECM) hydrogel, which can be injected into the joints and provide biomimetic microenvironments to drive cartilage regeneration. Benefiting from the cell-adaptable dynamic network and cartilage-specific compositions, the supramolecular dECM hydrogel not only enhances cell proliferation and migration, but also facilitates chondrogenesis. Furthermore, compared with the conventional dECM hydrogels, the supramolecular dECM hydrogel is instrumental in regulating inflammation, which consequently leads to a marked suppression of genes linked to cell death and cartilage degradation. In vivo analysis confirms that stem cells, when delivered via the supramolecular dECM hydrogel, remain viable for up to three months within the restored cartilage. The regenerated tissue exhibits hyaline-cartilage structure, good mechanical properties, and cartilage-specific extracellular matrix deposition that align closely with those of native cartilage. We envision that this supramolecular dECM hydrogel could serve as a valuable platform for cartilage regeneration and could strongly facilitate the clinical translation of dECM-based materials for tissue regeneration.

Pathological progress and remission strategies of osteoarthritic lesions caused by long-term joint immobilization

ObjectiveWhile joint immobilization is a useful repair method for intra-articular ligament injury and periarticular fracture, prolonged joint immobilization can cause multiple complications. A better understanding how joint immobilization and remobilization impact joint function and homeostasis will help clinicians develop novel strategies to reduce complications.DesignWe first determined the effects of long-term immobilization on joint pain and osteophyte formation in patients after an extraarticular fracture or ligament injury. We then developed a mouse model of joint immobilization and harvested the knee joint samples at 2, 4, and 8 weeks. We further determined the effects of remobilization on recovery of the osteoarthritis (OA) lesions induced by immobilization in mice.ResultsWe found that the long-term (6 weeks) joint immobilization caused significant joint pain and osteophytes in patients. In mice, 2-week immobilization already induced moderate sensory innervation and increased pain sensitivity and infiltration in synovium without inducing marked osteophyte formation and cartilage loss. Long-term immobilization (4 and 8 weeks) induced more severe sensory innervation and inflammatory infiltration in synovium, massive osteophyte formation on both sides of the femoral condyle, and the edge of the tibial plateau and significant loss of the articular cartilage in mice. Remobilization, which ameliorates normal joint load and activity, restored to certain extent some of the OA lesions and joint function in mice.ConclusionsJoint immobilization caused multiple OA-like lesions in both mice and humans. Joint immobilization induced progressive sensory innervation, synovitis, osteophyte formation, and cartilage loss in mice, which can be partially ameliorated by remobilization.

Barasertib impedes chondrocyte senescence and alleviates osteoarthritis by mitigating the destabilization of heterochromatin induced by AURKB

Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage loss that causes disability worldwide. The accumulation of senescent chondrocytes in aging human cartilage contributes to the high incidence of OA. Heterochromatin instability, the hallmark and driving factor of senescence, regulates the expression of the senescence-associated secretory phenotype that induces inflammation and cartilage destruction. However, the role of heterochromatin instability in OA progression remains unclear. In this work, we identified AURKB as a key senescence-associated chromatin regulator using bioinformatics methods. We found that AURKB was upregulated in OA cartilage and chondrocytes exposed to abnormal mechanical strain. Overexpression of AURKB could cause senescence and heterochromatin instability. Furthermore, the AURKB inhibitor Barasertib reversed senescence and heterochromatin instability in chondrocytes and alleviated OA in a rat model. Mechanistically, abnormal mechanical strain increased AURKB levels through the Piezo1/Ca2+ signaling axis. Blocking Piezo1/Ca2+ signaling by short interfering RNA against Piezo1 and Ca2+ chelator BAPTA could reduce the expression of AURKB and alleviate senescence in chondrocytes exposed to abnormal mechanical strain. In conclusion, our data confirmed that abnormal mechanical strain increases the expression of AURKB by activating the Piezo1/Ca2+ signaling axis, leading to destabilized heterochromatin and senescence in chondrocytes, whereas Barasertib consolidates heterochromatin, counteracts senescence and alleviates OA.

Added Value of MRI Knee Cartigram in Assessment of Anterior Knee Pain in Comparison to Conventional Standard MRI

Background Osteoarthritis (OA) is a multi-tissue, multi-factorial disease and worldwide a major cause of disability resulting from reduced joint mobility and function. Progressive loss of hyaline cartilage is one of the hallmark features of osteoarthritis, initiated by a loss of proteoglycans and an increase in water content, followed by a loss of type II collagen and a change in collagen fiber orientation. Objective To evaluate the role of T2 mapping in detection of degenerative changes in articular cartilage of knee joint as compared to standard clinical magnetic resonance imaging (MRI) at 1.5T. Patients and Methods From April 2020 to November 2020, this prospective Study was done to use T2 mapping to visualize the articular cartilage of the knee on 1.5 T MR Scanner using special software to evaluate the efficiency Of T2 mapping to detect cartilage lesions. The material of this study included 380 patients. The study includes all of them come complaining of knee pain and 2 of them had previous minor knee trauma, each patient had a single MRI exanimation including conventional MRI routine protocol and added a single complementary T2 mapping. Results there were significant differences between T2 mapping and conventional MRI sequence in the ability to detect cartilage degeneration as T2 mapping was capable of detecting all lesions that were visible on the clinical MRI. Moreover, T2 mapping showed more cartilage lesions than clinical MRI T2 mapping showed more cartilage lesions than clinical MRI, and in T2 maps the lesions appeared generally wider. This proposes that T2 mapping is feasible in the clinical setting and may reveal cartilage lesions not seen on the standard knee MRI. Conclusion Our results suggest that T2 mapping is an interesting MRI sequence for the exploration of patients articular cartilage in and should be included in the routine protocol if cartilage pathology is suspecting as it may improve the diagnostic accuracy of MRI for focal chondral lesions, and should help decide whether and MR-arthrography or CT-arthrography is necessary.

Erythrocyte membrane-camouflaged and double-factor sequential delivery nanocarriers postpone the progression of osteoarthritis

Osteoarthritis is a commonly severe joint disease featured by the progressive loss of cartilage and reduction in lubricating synovial fluid, which currently lacks the effective treatment in clinic. Herein, we designed an erythrocyte membrane-camouflaged and double-factor sequential delivery of shell-core nanocarrier to deliver two diverse drugs. The interior core of nanocarriers was loaded with the transforming growth factor-β3 (TGF-β3), and subsequently modified with a natural anti-inflammatory drug of curcumin, and finally encapsulated with erythrocyte membrane as a protective and regulation shell. The as-prepared engineered nanocarriers were injected into joint capsule to play a dual function on inflammation modulation and cartilage remodeling. The curcumin absorbed on the internal surface of shell membrane was firstly released in large quantities to tune the inflammatory microenvironment whereas the TGF-β3 in the interior core was released subsequently with the nanoparticle degradation to alleviate chondrocyte senescence. Overall, our current work creates an engineered nanocarrier to control macrophage type and induce cartilage restoration on postponing the progression of osteoarthritis.

The Endocannabinoid System a Turning Point in Optimizing Physiotherapy Procedures in Knee Osteoarthritis

Introduction: Knee Osteoarthritis (KOA) is characterized by wear, tear, and it's a slowly progressive loss of cartilage, that becomes finally disabling. KOA is one of the most analyzed diseases by many medical specialties such as rheumatology, orthopedics, rehabilitation medicine, and physiotherapy. Major symptoms of KOA such as pain, dysfunction, and chronic low-grade inflammation will decrease the quality of life and eventually lead to locomotor disability. Since there are no effective ways to limit KOA progression, involvement of the endocannabinoid system (ECS) may be a non-pharmacological therapeutic alternative in the management of this disease. This study debate aspects of ways to modulate the ECS in KOA, using physiotherapeutic (PT) means such as TENS electroanalgesia, LASER biostimulation, and physical exercises with analgesic effects. Materials and Methods: In the study, we included 82 sources, with the following keywords in the title: knee osteoarthritis, cannabidiol, endocannabinoid, inflammatory pain, analgesia, neuropathic pain, physiotherapy, electrotherapy, and LASER. To perform this review, we searched for the most relevant articles in the field of medicine and physiotherapy in 7 international databases applying inclusion and exclusion criteria. Results: The application of TENS currents in certain doses and frequencies together with LASER biostimulation stimulates the production of endocannabinoids thus controlling pain, and stimulating the ECS. Physical exercise has an antioxidant, and anti-inflammatory role and stimulates the release of endogenous opioids. Conclusions: The results obtained from this meta-analysis may contribute to paradigm shifts in clinical practice related to the treatment of pain by PT. TENS, LASER, and physical exercise are effective clinical tool that limits chronic inflammation and pain by involving the ECS. More studies are needed to understand endocannabinoid system involvements in KOA, and that will inspire medical doctors and physiotherapists to improve long-term treatment strategies.

Comparison of the effects of oxidative and inflammatory stresses on rat chondrocyte senescence

Osteoarthritis (OA) is an age-related degenerative joint disease that causes progressive cartilage loss. Chondrocyte senescence is a fundamental mechanism that contributes to the imbalance of matrix homeostasis in OA by inducing senescence-associated secretory phenotype (SASP). Although OA chondrocytes are mainly exposed to oxidative and inflammatory stresses, the role of these individual stresses in chondrocyte senescence remains unclear. In this study, we compared the effects of these stresses on the senescence of rat chondrocytes. Rat chondrocytes were treated with H2O2 and a combination of IL-1β and TNF-α (IL/TNF) to compare their in vitro effect on senescent phenotypes. For in vivo evaluation, H2O2 and IL/TNF were injected into rat knee joints for 4 weeks. The in vitro results showed that H2O2 treatment increased reactive oxygen species, γ-H2AX, and p21 levels, stopped cell proliferation, and decreased glycosaminoglycan (GAG)-producing ability. In contrast, IL/TNF increased the expression of p16 and SASP factors, resulting in increased GAG degradation. Intraarticular injections of H2O2 did not cause any changes in senescent markers; however, IL/TNF injections reduced safranin O staining and increased the proportion of p16- and SASP factor-positive chondrocytes. Our results indicate that oxidative and inflammatory stresses have significantly different effects on the senescence of rat chondrocytes.

Potential of Phytomolecules in Alliance with Nanotechnology to Surmount the Limitations of Current Treatment Options in the Management of Osteoarthritis.

Osteoarthritis (OA), a chronic degenerative musculoskeletal disorder, progressively increases with age. It is characterized by progressive loss of hyaline cartilage followed by subchondral bone remodeling and inflammaging. To counteract the inflammation, synovium releases various inflammatory and immune mediators along with metabolic intermediates, which further worsens the condition. However, even after recognizing the key molecular and cellular factors involved in the progression of OA, only disease-modifying therapies are available such as oral and topical NSAIDs, opioids, SNRIs, etc., providing symptomatic treatment and functional improvement instead of suppressing OA progression. Long-term use of these therapies leads to various life-threatening complications. Interestingly, mother nature has numerous medicinal plants containing active phytochemicals that can act on various targets involved in the development and progression of OA. Phytochemicals have been used for millennia in traditional medicine and are promising alternatives to conventional drugs with a lower rate of adverse events and efficiency frequently comparable to synthetic molecules. Nevertheless, their mechanism of action in many cases is elusive and uncertain. Even though many in vitro and in vivo studies show promising results, clinical evidence is scarce. Studies suggest that the presence of carbonyl group in the 2nd position, chloro in the 6th and an electron- withdrawing group at the 7th position exhibit enhanced COX-2 inhibition activity in OA. On the other hand, the presence of a double bond at the C2-C3 position of C ring in flavonoids plays an important role in Nrf2 activation. Moreover, with the advancements in the understanding of OA progression, SARs (structure-activity relationships) of phytochemicals and integration with nanotechnology have provided great opportunities for developing phytopharmaceuticals. Therefore, in the present review, we have discussed various promising phytomolecules, SAR as well as their nano-based delivery systems for the treatment of OA to motivate the future investigation of phytochemical-based drug therapy.

Correlation of Toe Grip Strength among Individuals with Knee Osteoarthritis with and without Fear of Pain: A Cross-sectional Study

Introduction: Knee Osteoarthritis (OA) is a common degenerative joint disease that affects millions of people worldwide. It is characterised by progressive loss of joint cartilage, resulting in pain, stiffness, and significant disability, leading to a reduced quality of life. Fear of pain is a significant psychosocial factor that affects individuals with knee OA, leading to decreased physical activity. However, the relationship between Toe Grip Strength (TGS) and fear of pain in individuals with knee OA is poorly understood, even though fear of pain has been known to impact strength in both the upper and lower limbs. Aim: To examine the correlation between fear and TGS among individuals with knee OA, both with and without fear of pain. Materials and Methods: This cross-sectional study was conducted at the Department of Physiotherapy, Nitte Institute of Physiotherapy, affiliated with the University of Mangalore, Karnataka, India, from April 2022 to March 2023. The study included 60 individuals, with 30 in each group, diagnosed with knee OA using the Kellgren and Lawrence (KL) grading system (grade 2 and above). The participants, both men and women aged between 45 and 80 years, were informed about the study’s purpose. The Fear Avoidance Belief Questionnaire (FABQ) form was completed by the screened patients, who were then divided into fear and non fear groups. Body Mass Index (BMI) was determined by measuring height with a wall-mounted device and weight using a traditional analog scale. TGS was evaluated in both groups using a pinch grip dynamometer. The Pearson correlation coefficient was used for data analysis, with a p-value <0.05 considered statistically significant. Results: The results of the current study indicated that the FABQ showed a negative correlation (p-value >0.05) with TGS (both right and left-side) (r: -0.296 (right) and -0.302 (left)), and a positive correlation (p-value<0.05) with the Numerical Pain Rating Scale (NPRS) (both during activity and at rest). Conclusion: This study revealed a significant association between fear and TGS in individuals with knee OA. Notably, Fear Avoidance Beliefs (FAB) exhibited a negative correlation with TGS while demonstrating a positive correlation with pain levels.

The Effect of Low Dose Methotrexate in Rheumatoid arthritis Bangladeshi Patients

Background: Rheumatoid arthritis is a painful, disabling joint condition characterized by synovium growth and progressive cartilage and bone loss. Methotrexate (MTX) has been used to treat Rheumatoid Arthritis (RA) for over three decades. Because it improves symptoms, signs, disease activity, and functions, it is one of the most effective and widely used Disease Modifying Antirheumatic Drugs (DMARDS). Objective: In this study our main goal is to evaluate the effect of low dose Methotrexate in Rheumatoid arthritis. Method: This cross-sectional study was carried out at tertiary medical hospital from June 2021 to June 2022. Where a total of 100 patients of Rheumatoid Arthritis were attended OPD were included as a sample size. Patients were prescribed low dose methotrexate 5-10mg/ week. Folate supplementation in the form of folic acid was also given to all patients. Results: During the study, majority were belonging to >60 years age group, 65% and most of them were male. 80% had high APR before treatment and 35% had low APR after treatment with MTX. 70% had swollen joints and 80% had tender joints before treatment. After treatment it reduced to 11% swollen joints and 45% tender joints. Moreover, At 0 week, 55% patients were in high disease activity (DAS 28>5.1), 43% patients were in moderate disease activity (DAS 28 between 3.2-5.1) and 2% patients were in low disease activity (DAS 28 <3.2). AT 4th week, 20% were in high disease activity, 65% were in moderate disease activity and 15% were in low disease activity. At 8th week, 70% were in moderate disease activity and 30% were in low disease activity. At 12th weeks, 60% were in moderate disease activity and 40% were in low disease activity. Conclusion: From our study, we found that low-dose MTX improves symptoms, signs, disease activity, and functions, and that early management with DMARDs in annual RA provides the least possibility for disease remission.

Therapeutic applications of adipose-derived stromal vascular fractions in osteoarthritis.

Osteoarthritis (OA) is considered to be a highly heterogeneous disease with progressive cartilage loss, subchondral bone remodeling, and low-grade inflammation. It is one of the world's leading causes of disability. Most conventional clinical treatments for OA are palliative drugs, which cannot fundamentally cure this disease. The stromal vascular fraction (SVF) from adipose tissues is a heterogeneous cell population. According to previous studies, it contains a large number of mesenchymal stem cells, which have been used to treat OA with good therapeutic results. This safe, simple, and effective therapy is expected to be applied and promoted in the future. In this paper, the detailed pathogenesis, diagnosis, and current clinical treatments for OA are introduced. Then, clinical studies and the therapeutic mechanism of SVF for the treatment of OA are summarized.

Unbiased transcriptome mapping and modeling identify candidate genes and compounds of osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage loss, subchondral bone remodeling, and synovial inflammation. Given that the current therapies for advanced OA patients are limited, the understanding of mechanisms and novel therapies are urgently needed. In this study, we employed the weighted gene co-expression network (WGCNA) method and the connectivity map (CMap) database to identify the candidate target genes and potential compounds. Four groups of co-expressing genes were identified as the OA-related modules. The biological annotations of these modules indicated some critical hallmarks of OA and aging, such as mitochondrial dysfunctions and abnormal energy metabolism, and the signaling pathways, such as MAPK, TNF, and PI3K/Akt signaling pathways. Some genes, such as RELA and GADD45B, were predicted to extensively involve these critical pathways, indicating their potential functions in OA mechanisms. Moreover, we constructed the co-expressing networks of modules and identified the hub genes based on network topology. GADD45B, MAFF, and MYC were identified and validated as the hub genes. Finally, anisomycin and MG-262 were predicted to target these OA-related modules, which may be the potential drugs for OA therapy. In conclusion, this study identified the significant modules, signaling pathways, and hub genes relevant to OA and highlighted the potential clinical value of anisomycin and MG-262 as novel therapies in OA management.

Zoledronic acid generates a spatiotemporal effect to attenuate osteoarthritis by inhibiting potential Wnt5a-associated abnormal subchondral bone resorption.

This study aimed to determine the effects of zoledronic acid (ZOL) on OA in rats and explored the molecular mechanism of osteoclast activation in early OA. A knee OA rat model was designed by surgically destabilizing the medial meniscus (DMM). Seventy-two male rats were randomly assigned to Sham+phosphate-buffered saline (PBS), DMM+PBS, and DMM+ZOL groups; rats were administered with 100 μg/Kg ZOL or PBS, twice weekly for 4 weeks. After 2, 4, 8, and 12 weeks of OA induction, the thickness of the hyaline and calcified cartilage layers was calculated using hematoxylin and eosin staining, degenerated cartilage stained with Safranin O-fast green staining was evaluated and scored, tartrate-resistant acid phosphatase (TRAP)-stained osteoclasts were counted, changes in subchondral bone using micro-computed tomography were analyzed, and PINP and CTX-I levels were detected using enzyme-linked immunosorbent assay. Using these results, 18 male rats were randomly assigned to three groups. Four weeks after surgery, Wnt5a, RANKL, CXCL12, and NFATc1 protein levels were measured in subchondral bone using western blotting, and mRNA levels of genes related to osteoclastogenesis in subchondral bone were measured using quantitative polymerase chain reaction. Bone marrow-derived macrophages were isolated as osteoclast precursors, and cell differentiation, migration, and adhesion were assessed by TRAP staining and Transwell assays, revealing that DMM induced knee OA in rats. Progressive cartilage loss was observed 12 weeks after OA induction. Subchondral bone remodeling was dominated by bone resorption during early OA (within 4 weeks), whereas bone formation was increased 8 weeks later. ZOL suppressed bone resorption by inhibiting Wnt5a signaling in early OA, improved the imbalance of subchondral bone remodeling, reduced cartilage degeneration, and delayed OA progression. Additionally, ZOL delayed OA progression and reduced cartilage degeneration via a spatiotemporal effect in DMM-induced OA. Osteoclast activity in early OA might be associated with Wnt5a signaling, indicating a possible novel strategy for OA treatment.

Local Drug-Induced Modulation of gp130 Receptor Signaling Delays Disease Progression in a Pig Model of Temporo-Mandibular Joint Osteoarthritis

Temporomandibular joint disorders (TMJs) are a multifaceted group of chronic disorders characterized by stiffness in the jaw, limited jaw mobility and pain when opening or closing the mouth. TMJs are relatively common, with incidence rates in the range of 5–12%, with nearly twice as many women as men being affected. One of the primary causes of TMJs is a degenerative disease of joints, such as osteoarthritis (OA), characterized by progressive loss of cartilage which causes stiffness, swelling, and pain. Currently, there are no disease-modifying agents on the market for OA. We have recently discovered a small molecule, R805 acting as a modulator of glycoprotein 130 (gp130) receptor for IL-6 family of cytokines. R805 enables regenerative outputs of endogenous joint stem and progenitor cells through immunomodulation in the joint microenvironment by reducing the levels of destructive cytokines and supporting chondrocyte survival and anabolism. Extensive testing has shown R805 to be safe at doses far above the therapeutic level. Here, we have conducted a pivotal efficacy study in our newly-established pig model of TMJ post-traumatic OA. IA injection of R805 has shown a highly significant reduction of articular cartilage degeneration, reduced synovitis and degenerative changes in subchondral bone in the mandibular condyle compared to the vehicle-treated group. These data will support additional pre-clinical development of R805 as a first-in-class injectable therapeutic for TMJ osteoarthritis.

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint (TMJ) osteoarthritis (OA); however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4 (Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2 and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore, Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

Clearance of senescent cells with ABT-263 improves biological functions of synovial mesenchymal stem cells from osteoarthritis patients

BackgroundOsteoarthritis (OA) is an age-related joint disease characterized by progressive cartilage loss. Synovial mesenchymal stem cells (MSCs) are anticipated as a cell source for OA treatment; however, synovial MSC preparations isolated from OA patients contain many senescent cells that inhibit cartilage regeneration through their senescence-associated secretory phenotype (SASP) and poor chondrogenic capacity. The aim of this study was to improve the biological function of OA synovial MSCs by removing senescent cells using the senolytic drug ABT-263.MethodsWe pretreated synovial MSCs derived from 5 OA patients with ABT-263 for 24 h and then evaluated senescence-associated beta-galactosidase (SA-β-gal) activity, B cell lymphoma 2 (BCL-2) activity, apoptosis, surface antigen expression, colony formation ability, and multipotency.ResultsThe ABT-263 pretreatment significantly decreased the percentage of SA-β-gal-positive cells and BCL-2 expression and induced early- and late-stage apoptosis. Cleaved caspase-3 was expressed in SA-β-gal-positive cells. The pretreated MSCs formed greater numbers of colonies with larger diameters. The expression rate of CD34 was decreased in the pretreated cells. Differentiation assays revealed that ABT-263 pretreatment enhanced the adipogenic and chondrogenic capabilities of OA synovial MSCs. In chondrogenesis, the pretreated cells produced greater amounts of glycosaminoglycan and type II collagen and showed lower expression of senescence markers (p16 and p21) and SASP factors (MMP-13 and IL-6) and smaller amounts of type I collagen.ConclusionPretreatment of synovial MSCs from OA patients with ABT-263 can improve the function of the cells by selectively eliminating senescent cells. These findings indicate that ABT-263 could hold promise for the development of effective cell-based OA therapy.

Medial meniscus extrusion and varus tilt of joint line convergence angle increase stress in the medial compartment of the knee joint in the knee extension position -finite element analysis-

PurposeAlthough it has been recognized that the medial meniscus extrusion (MME) leads to progressive cartilage loss and osteoarthritis (OA), about 20% of cases with MME had minor symptoms and poor progression of knee OA. However, it is still unclear which patients will have minimal symptoms or will not progress to degeneration. The purpose of this study is to compare the effect of the relationship between the MME and Joint line convergence angle (JLCA) on knee stress with the finite element (FE) analysis method.MethodsThe 65 year-old female was taken computer tomography (CT) from thigh to ankle. A 3-dimentional nonlinear FE model was constructed from the patient’s DICOM data. We made the six models, which was different from JLCA and MME. Contact stresses on the surfaces between femoral and tibial cartilages and both side of meniscus are analyzed.ResultsAs the JLCA or MME increased, the stress load on the medial compartment increased. The effect of MME was stronger on the femoral side, while the effect of JLCA was stronger for the tibia and meniscus. If the JLCA was tilted valgus, the stress in the medial compartment did not increase even in the presence of MME.ConclusionsThis study revealed that the MME is associated with increased a stress loading on medial compartment structures. Furthermore, this change was enhanced by the varus tilt of the JLCA. In the case of valgus alignment, the contact pressure of the medial compartment did not increase so much even if with the MME.Level of evidenceLevel V

The Role of Inflammasomes in Osteoarthritis and Secondary Joint Degeneration Diseases.

Osteoarthritis is age-related and the most common form of arthritis. The main characteristics of the disease are progressive loss of cartilage and secondary synovial inflammation, which finally result in pain, joint stiffness, and functional disability. Similarly, joint degeneration is characteristic of systemic inflammatory diseases such as rheumatoid arthritis and gout, with the associated secondary type of osteoarthritis. Studies suggest that inflammation importantly contributes to the progression of the disease. Particularly, cytokines TNFα and IL-1β drive catabolic signaling in affected joints. IL-1β is a product of inflammasome activation. Inflammasomes are inflammatory multiprotein complexes that propagate inflammation in various autoimmune and autoinflammatory conditions through cell death and the release of inflammatory cytokines and damage-associated molecule patterns. In this article, we review genetic, marker, and animal studies that establish inflammasomes as important drivers of secondary arthritis and discuss the current evidence for inflammasome involvement in primary osteoarthritis. The NLRP3 inflammasome has a significant role in the development of secondary osteoarthritis, and several studies have provided evidence of its role in the development of primary osteoarthritis, while other inflammasomes cannot be excluded. Inflammasome-targeted therapeutic options might thus provide a promising strategy to tackle these debilitating diseases.

The Effect of Slow Stroke Back Massage Cutaneus Stimulation on Pain Intensity Osteoarthritis in The Elderly

Osteoarthritis (OA) also known as degenerative joint disease is the most common in all forms of arthritis and causes pain and disability in the elderly. This disease is characterized by progressive loss of joint cartilage, synovitis (inflammation of the synovium lining the joints), joint pain, stiffness, and loss of joint movement (Lemone, 2018:1679). Skin stimulation that can be done is Slow-Stroke Back Massage. Proper use of skin stimulation: slow-stroke back massage can reduce pain perception and help reduce muscle tension which can reduce pain intensity, but it can also cause dilation of blood vessels and improve blood circulation in tissues. This activity was carried out at the Lubuk Pakam Health Center in January 2021. The target of this community service is 30 elderly people with osteoarthritis. The method used in this community service is providing education or counseling to patients with Osteoarthritis. The media used are Power point presentation (PPT) and LCD for approximately 90 minutes. To measure the success of the education or counseling provided, knowledge measurement before and after education or counseling was carried out using a questionnaire. Data analysis for bivariate calculations in this study used Pair Samples t-test with the provisions of 0.05. Based on the results of statistical tests using paired sample t-test, p value (= 0.000) < (= 0.05) it can be concluded that the hypothesis in this study is accepted,

Stem cell-homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model.

Osteoarthritis (OA) is a common joint disease characterized by progressive loss of cartilage and reduction in lubricating synovial fluid, which lacks effective treatments currently. Here, we propose a hydrogel-based miRNA delivery strategy to rejuvenate impaired cartilage by creating a regenerative microenvironment to mitigate chondrocyte senescence that mainly contributes to cartilage breakdown during OA development. An aging-related miRNA, miR-29b-5p, was first found to be markedly down-regulated in OA cartilage, and their up-regulation suppressed the expression of matrix metalloproteinases and senescence-associated genes (P16INK4a/P21) via ten-eleven-translocation enzyme 1 (TET1). An injectable bioactive self-assembling peptide nanofiber hydrogel was applied to deliver agomir-29b-5p, which was functionalized by conjugating a stem cell–homing peptide SKPPGTSS for endogenous synovial stem cell recruitment simultaneously. Sustained miR-29b-5p delivery and recruitment of synovial stem cells and their subsequent differentiation into chondrocytes led to successful cartilage repair and chondrocyte rejuvenation. This strategy enables miRNA-based therapeutic modality to become a viable alternative for surgery in OA treatment.