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Összefoglaló. Az arthrosis az ízületeket alkotó porc, csont és a környező lágy részek leépülésével járó betegség. A betegség jelentős fájdalommal jár, progresszív, az ízület strukturális átalakulását és ennek következtében jelentős funkcióvesztést és életminőség-romlást okoz. Kialakulásában immunológiai gyulladásos folyamatok is szerepet játszanak, amelyek befolyásolása lehetőséget ad nemcsak tüneti kezelésre, hanem betegségmódosító terápia kialakítására is. A nem denaturált 2-es típusú kollagén oralis alkalmazása szisztémás toleranciát hoz létre, ami a proinflammatoricus folyamatok gátlása és az antiinflammatoricus hatások erősítése révén új lehetőség az immunmodulációra. A klinikai vizsgálatok a betegeknél a fájdalom jelentős csökkenéséről, a mozgásszervek funkciójának javulásáról számolnak be, és a kezelés egészséges ízületben is nyújthat védelmet a mechanikus stressz okozta ízületi károsodással szemben. Orv Hetil. 2021; 162(37): 1481–1484. Summary. Osteoarthritis is a disease of the cartilage, bone and surrounding soft tissues that make up the joints. The disease is associated with significant pain, it is progressive, causing structural transformation of the joint and, as a result, significant loss of function and deterioration in the quality of life. Immunological inflammatory processes also play a role in its development, the influence of which allows not only symptomatic treatment, but also the development of disease-modifying therapy. Oral administration of undenatured type II collagen creates systemic tolerance, which is a new opportunity for immunomodulation by inhibiting proinflammatory processes and enhancing anti-inflammatory effects. Clinical trials have reported significant reduction in pain, improved musculoskeletal function in patients, and the therapy may provide protection against joint damage caused by mechanical stress in healthy joints. Orv Hetil. 2021; 162(37): 1481–1484.

Introduction. Osteoarthritis (OA) is generally a progressive disease that affects synovial joints, resulting in abnormalities to articular cartilage subchondral bone, synovium, and adjacent soft tissues. Aim. The purpose of this work was to examine the histological changes in knee cartilage and bone following the administration of two different chondroitin sulfate products in two experimental OA models in rats. Material and methods. OA was induced in rats by either a single injection of mono-iodoacetate or four once-weekly injections of dexamethasone. 70 adult rats were included: 30 received mono-iodoacetate, 30 received dexamethasone and the 10 remaining controls received no injection. Samples of knee bone and cartilage were then analyzed histologically. Results. Animals with OA that received CS had significantly less inflammation, improved motor activity, and better analgesia compared with those that did not receive CS, with little difference between products. Histologically, both products reduced the signs of OA and resulted in the activation of regenerative processes of cartilage and bone and stimulation of proliferation and formation of amorphous material. Conclusion. These results substantiate the importance of using high-quality pharmaceutical-grade CS to ensure optimal efficacy and safety of the final product in patients with OA.

The literature was reviewed for reports on the pathogenesis, diagnosis and treatment of injuries to the posterior cruciate ligament (PCL). PCL is the largest intra-articular ligament in the knee joint and has good tensile mechanical properties. Optimal diagnosis and appropriate treatment strategies for PCL injury are discussed. Nonoperative treatment of isolated PCL injuries is associated with a significant risk of degeneration of the knee structures and impaired function. A comprehensive line of PCL reconstruction options are offered for the surgical approach to PCL reconstruction to restore functional joint stability in the knee. Literature data on protective effect of glucosamine, chondroitin sulfate in the prevention of secondary knee osteoarthritis caused by PCL ruptures were reviewed.

ObjectivesAlthough treatment development in osteoarthritis (OA) focuses on chondroprotection, it is unclear how much preventing cartilage loss reduces joint pain. It is also unclear how nociceptive tissues may be involved.MethodsUsing data from the Osteoarthritis Initiative, we quantified the relation between cartilage loss and worsening knee pain after adjusting for bone marrow lesions (BMLs) and synovitis, and examined how much these factors mediated this association. 600 knee MRIs were scored at baseline, 12 months and 24 months for quantitative and semiquantitative measures of OA structural features. We focused on change in medial cartilage thickness using an amount similar to that seen in recent trials. Linear models calculated mean change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score with cartilage loss, adjusted for baseline BMLs, synovitis and covariates. Mediation analysis tested whether change in synovitis or BMLs mediated the cartilage loss–pain association. We carried out a subanalysis for knees with non-zero baseline WOMAC pain scores and another for non-valgus knees.ResultsCartilage thickness loss was significantly associated with a small degree of worsening in pain over 24 months. For example, a loss of 0.1 mm of cartilage thickness over 2 years was associated with a 0.32 increase in WOMAC pain (scale 0–20). The association of cartilage thickness loss with pain was mediated by synovitis change but not by BML change. Subanalysis results were similar.ConclusionsCartilage thickness loss is associated with only a small amount of worsening knee pain, an association mediated in part by worsening synovitis. Demonstrating that chondroprotection reduces knee pain will be extremely challenging and is perhaps unachievable.

Background: Osteoarthritis is a chronic progressive disease commonly affecting the hip and knee joints. Although many drugs are available and afford symptomatic relief, their side effects pose limitations to their continuous use. Introduction: Myostaal Forte (MF) is a poly-herbal Ayurvedic formulation that has shown protection against damage to the chondrocyte layer on histopathological examination in previous studies. But biomarkers which are indicative of chondroprotection have not been assessed. So, the present study was planned to reconfirm the protective effect of MF in osteoarthritic rats by histopathology and create a more substantial evidence by assessing the levels of Cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase-13 (MMP-13). Methods: 32 rats were divided into four groups (n = 8 each group); sham control (SC), disease control (DC), positive control (PC) and a MF group. Behavioural tests were compared from baseline to 7th day, 14th day, 21st day and on 28th day. Histopathology and bone markers were compared on the 28th day. p

Rheumatoid arthritis (RA) is a systemic disease characterized by autoimmunity, joint inflammation, and cartilage destruction, which affects 0.5-1% of the population. Many compounds from herbal medicines show the potentials to treat RA. On this basis, the compounds with good pharmacokinetic behaviors and drug-likeness properties will be further studied and developed. Therefore, the herbal compounds with anti-RA activities were reviewed in this paper, and the cheminformatics tools were used to predict their drug-likeness properties and pharmacokinetic parameters. A total of 90 herbal compounds were analyzed, which were reported to be effective on RA models through anti-inflammation, chondroprotection, immunoregulation, antiangiogenesis, and antioxidation. Most of the herbal compounds have good drug-likeness properties. Most of the compounds can be an alternative and valuable source for anti-RA drug discovery.

Osteoarthritis (OA) is a joint degenerative disease that is an exceedingly common problem associated with aging. Aging is the principal risk factor for OA, but damage-related physiopathology of articular chondrocytes probably drives the mechanisms of joint degeneration by a progressive decline in the homeostatic and regenerative capacity of cells. Cellular aging is the manifestation of a complex interplay of cellular and molecular pathways underpinned by transcriptional, translational, and epigenetic mechanisms and niche factors, and unraveling this complexity will improve our understanding of underlying molecular changes that affect the ability of the articular cartilage to maintain or regenerate itself. This insight is imperative for developing new cell and drug therapies for OA disease that will target the specific causes of age-related functional decline. This review explores the key age-related changes within articular chondrocytes and discusses the molecular mechanisms that are commonly perturbed as cartilage ages and degenerates. Current efforts and emerging potential therapies in treating OA that are being employed to halt or decelerate the aging processes are also discussed.

Osteoarthritis (OA) is a degenerative joint disease and an important cause of incapacitation. There is a lack of drugs and effective treatments that stop or slow the OA progression. Modern pharmacological treatments, such as analgesics, have analgesic effects but do not affect the course of OA. Long-term use of these drugs can lead to serious side effects. Given the OA nature, it is likely that lifelong treatment will be required to stop or slow its progression. Therefore, there is an urgent need for disease-modifying OA treatments that are also safe for clinical use over long periods. Phytonutraceuticals are herbal products that provide a therapeutic effect, including disease prevention, which not only have favorable safety characteristics but may have an alleviating effect on the OA and its symptoms. An estimated 47% of OA patients use alternative drugs, including phytonutraceuticals. The review studies the efficacy and action mechanism of widely used phytonutraceuticals, analyzes the available experimental and clinical data on the effect of some phytonutraceuticals (phytoflavonoids, polyphenols, and bioflavonoids) on OA, and examines the known molecular effect and the possibility of their use for chondroprotection.

This chapter describes chronic and acute chondral damage. Clinical history, etiology, and associated pathologies are discussed. Indications and contraindications for nonoperative management are reviewed. Nonoperative management is discussed in detail and operative treatment is described briefly, highlighting the most up-to-date level one evidence. Treatment algorithms are provided with a focus on nonoperative techniques. Outcomes are discussed. Future directions are presented and the author’s algorithm is presented. This chapter is based on the framework of chondroprotection, chondrofacilitation, and resurfacing.

Osteoarthritis (OA) is the most common type of arthritis that occurs in an aged population. It affects any joints in the body and degenerates the articular cartilage and the subchondral bone. Despite the pathophysiology of OA being different, cartilage resorption is still a symbol of osteoarthritis. Matrix metalloproteinases (MMPs) are important proteolytic enzymes that degrade extra-cellular matrix proteins (ECM) in the body. MMPs contribute to the turnover of cartilage and its break down; their levels have increased in the joint tissues of OA patients. Application of chondroprotective drugs neutralize the activities of MMPs. Natural products derived from herbs and plants developed as traditional medicine have been paid attention to, due to their potential biological effects. The therapeutic value of natural products in OA has increased in reputation due to their clinical impact and insignificant side effects. Several MMPs inhibitor have been used as therapeutic drugs, for a long time. Recently, different types of compounds were reviewed for their biological activities. In this review, we summarize numerous natural products for the development of MMPs inhibitors in arthritic diseases and describe the major signaling targets that were involved for the treatments of these destructive joint diseases.

Meniscal allograft transplantation yields good and excellent results but is limited by donor availability. The purpose of the study was to evaluate the effectiveness of radiated deep-frozen xenogenic meniscal tissue (RDF-X) as an alternative graft choice in meniscal transplantation. The xenogenic meniscal tissues were harvested from the inner 1/3 part of the porcine meniscus and then irradiated and deeply frozen. The medial menisci of rabbits were replaced by the RDF-X. Meniscal allograft transplantation, meniscectomy and sham operation served as controls. Only a particular kind of rabbit-anti-pig antibody (molecular ranging 60–80 kD) was detected in the blood serum at week 2. The menisci of the group RDF-X grossly resembled the native tissue and the allograft meniscus with fibrocartilage regeneration at postoperative 1 year. Cell incorporation and the extracellular matrix were mostly observed at the surface and the inner 1/3 part of the newly regenerated RDF-X, which was different from the allograft. The biomechanical properties of the group RDF-X were also approximate to those of the native meniscus except for the compressive creep. In addition, chondroprotection was achieved after the RDF-X transplantation although the joint degeneration was not completely prevented. To conclude, the RDF-X could be a promising alternative for meniscal transplantation with similar tissue regeneration capacity to allograft transplantation and superior chondroprotection. The potential minor immunological rejection should be further studied before its clinical application.

Background Osteoarthritis (OA) is a prevalent musculoskeletal disease resulting in progressive degeneration of the hyaline articular cartilage within synovial joints. Current repair treatments for OA often result in poor quality tissue that is functionally ineffective compared to the hyaline cartilage and demonstrates increased failure rates post-treatment. Complicating efforts to improve clinical outcomes, animal models used in pre-clinical research show significant heterogeneity in their regenerative and degenerative responses associated with their species, age, genetic/epigenetic traits, and context of cartilage injury or disease. These can lead to variable outcomes when testing and validating novel therapeutic approaches for OA. Furthermore, it remains unclear whether protection against OA among different model systems is driven by inhibition of cartilage degeneration, enhancement of cartilage regeneration, or any combination thereof. Main text Understanding the mechanistic basis underlying this context-dependent duality is essential for the rational design of targeted cartilage repair and OA therapies. Here, we discuss some of the critical variables related to the cross-species paradigm of degenerative and regenerative abilities found in pre-clinical animal models, to highlight that a gradient of regenerative competence within cartilage may exist across species and even in the greater human population, and likely influences clinical outcomes. Conclusions A more complete understanding of the endogenous regenerative potential of cartilage in a species specific context may facilitate the development of effective therapeutic approaches for cartilage injury and/or OA.

The meniscus is a crucial player in knee joint homeostasis. Loss of meniscus tissue can result in early onset of clinical symptoms like pain and loss of function, and structural degeneration of the articular cartilage. In case of a symptomatic segmental defect of the medial or lateral meniscus, different innovative options using biological or synthetic scaffolds are now available to regenerate meniscuslike tissue, with the aim of allowing a satisfactory clinical improvement to patients. However, the role of any of these procedures in terms of chondroprotection is questionable, and the overall outcomes in the long term still can be improved.

Extracorporeal shockwave therapy (ESWT) is a popular non-invasive therapeutic modality in the medical field for the treatment of numerous musculoskeletal disorders. This technique first emerged around the 1980s as extracorporeal shockwave lithotripsy and has been studied since then for its application towards orthopedics and traumatology. ESWT works by the emission of acoustic waves (shockwaves) that carry energy and can propagate through tissues. Shockwaves can generate interstitial and extracellular responses, producing many beneficial effects such as: pain relief, vascularization, protein biosynthesis, cell proliferation, neuro and chondroprotection, and destruction of calcium deposits in musculoskeletal structures. The combination of these effects can lead to tissue regeneration and significant alleviation of pain, improving functional outcomes in injured tissue. Considering these facts, ESWT shows great potential as a useful regenerative medicine technique for the treatment of numerous musculoskeletal injuries.

Background: Knee osteoarthritis (OA) is a common and often disabling joint disorder among adults that may result in impaired activity and daily function. A variety of treatment options are currently available and prescribed for knee OA depending on the severity of the disorder and physician preference. Intra-articular hyaluronic acid (IA-HA) injection is a treatment for knee OA that reportedly provides numerous biochemical and biological benefits, including shock absorption, chondroprotection, and anti-inflammatory effects within the knee. Clarity is needed as to whether the available IA-HA products should be considered for therapy as a group or whether there are significant differences in the products that need to be considered in treatment of OA of the knee. Purpose: To determine whether there are differences in efficacy and safety with respect to intrinsic properties of available IA-HA injections for knee OA. Study Design: Meta-analysis. Methods: A comprehensive literature search of the Medline, EMBASE, and PubMed databases was conducted for all existing randomized trials of IA-HA. The primary outcome measure analyzed was the mean pain score at the reported follow-up nearest to 26 weeks after injection. Pooled efficacy and safety results were recorded for subgroupings of HA product characteristics. Results: A total of 68 studies were included for analysis. Products with an average molecular weight ≥3000 kDa provided favorable efficacy results when compared with products of an average molecular weight Conclusion: Despite similarities, IA-HA products should not be treated as a group, as there are differences in IA-HA products that influence both efficacy and safety. In the available literature, IA-HA products with a molecular weight ≥3000 kDa and those derived from biological fermentation relate to superior efficacy and safety—factors that may influence selection an IA-HA product for OA of the knee.

We read with interest the recent article by Bacon et al 1 that used mediation analysis2 to understand the process by which cartilage loss changes joint pain. Given considerable investment in treatments that focus on chondroprotection, this is an important topic and the findings from this study have potential to inform patient management. The authors concluded that a small, non-clinically important effect of cartilage loss on joint pain was mediated by synovitis. To ensure this study accurately informs future research and practice, we ask the authors to clarify the reporting and interpretation of their results. The results presented in tables 3 and 4 do not support the authors conclusion that synovitis mediated the effect of cartilage loss on joint pain. The 95% …

Osteoarthritis (OA) is an inflammatory condition still lacking effective treatments. Mesenchymal stem/stromal cells (MSCs) have been successfully employed in pre-clinical models aiming to resurface the degenerated cartilage. In early-phase clinical trials, intra-articular (IA) administration of MSCs leads to pain reduction and cartilage protection or healing. However, the consistent lack of engraftment indicates that the observed effect is delivered through a “hit-and-run” mechanism, by a temporal release of paracrine molecules. MSCs express a variety of chemokines and cytokines that aid in repair of degraded tissue, restoration of normal tissue metabolism and, most importantly, counteracting inflammation. Secretion of therapeutic factors is increased upon licensing by inflammatory signals or apoptosis, induced by the host immune system. Trophic effectors are released as soluble molecules or carried by extracellular vesicles (ECVs). This review provides an overview of the functions and mechanisms of MSC-secreted molecules found to be upregulated in models of OA, whether using in vitro or in vivo models.

The reasonability of using nonsteroidal anti-inflammatory drugs (NSAIDs) in osteoarthritis (OA) is due mainly to persistent articular tissue inflammation that contributes to the progression of structural changes in the hyaline cartilage, as well as its leading clinical manifestation – pain syndrome caused by damage to different articular structures. NSAIDs are basic rapid-acting symptom-modifying drugs in the treatment of OA. Meloxicam has high anti-inflammatory and analgesic activities. The effect of meloxicam on hyaline cartilage metabolism permits one to consider it as a potential chondroprotective agent. Short- and long-term investigations have demonstrated its good tolerability, including that in patients with polymorbidity. The use of meloxicam does not increase the risk of cardiac and renal complications. The high therapeutic activity of meloxicam along with the low level of adverse reactions determines the pharmacoeconomic expediency of its use.

The anatomy and microstructure of the menisci allow the effective distribution of load across the knee. Meniscectomy alters the biomechanical environment and is a potent risk factor for osteoarthritis. Despite a trend towards meniscus-preserving surgery, many tears are irreparable, and many repairs fail.Meniscal allograft transplantation has principally been carried out for pain in patients who have had a meniscectomy. Numerous case series have reported a significant improvement in patient-reported outcomes after surgery, but randomised controlled trials have not been undertaken.It is scientifically plausible that meniscal allograft transplantation is protective of cartilage, but this has not been established clinically to date.Cite this article: Bone Joint J 2015; 97-B:590–4.

Arthroscopy of the synovial joint is the most frequently performed orthopaedic procedure in the developed world.[1][1] A variety of soft-tissue and articular pathologies relating to the hip,[2][2] knee, ankle, shoulder, elbow and wrist joints can be treated arthroscopically.[1][1] While advances in

Introduction: Myostaal Forte, a proprietary poly-herbal formulation, is mixture of nine herbal plant extracts which possess analgesic, anti-inflammatory and chondroprotective properties. Aim: A prospective, randomised, active controlled, 2-arm, parallel group, assessor blind study was planned to evaluate clinical efficacy and safety of Myostaal Forte in patients of knee osteoarthritis. Materials and Methods: Idiopathic knee osteoarthritis cases as per American College of Rheumatology (ACR) clinical criteria were screened and recruited. A total of sixty patients were assigned to receive Myostaal Forte TDS (n=30) or Paracetamol 650 mg TDS (n=30) for six weeks. Naproxen was rescue analgesia. Modified Western Ontario and McMaster Universities Arthritis Index (WOMAC), Visual Analogue Scale (VAS), global assessment scores determined by orthopaedic physician at baseline, two, four, six weeks and telephonically at eight weeks. Safety was assessed through laboratory investigations at baseline and six weeks, adverse events and tolerability. Data were expressed as Mean±SD and analysed by Chi-square and unpaired t-test. p0.05). No significant adverse events, changes in the laboratory parameters and excellent compliance to treatment were seen in both the groups. Conclusion: Earlier onset analgesic effect with sustained chondroprotection after treatment cessation makes Myostaal Forte, a safe and effective alternative for treatment of knee osteoarthritis.

Drilling into cartilage/bone is often required for orthopaedic surgery. While drilling into bone has been studied, the response of cartilage has received little attention. We have measured cartilage and drill bit temperatures during drilling and quantified the zone of chondrocyte death (ZCD) around the hole in the presence/absence of irrigation solutions.Drilling was performed using a 1.5-mm orthopaedic drill bit applied to bovine metatarsophalangeal joints and temperatures recorded by infrared camera. Osteochondral explants were then incubated with 5-chloromethylfluorescein diacetate (CMFDA) and propidium iodide (PI) to label living/dead chondrocytes respectively. The width of the ZCD was quantified by confocal laser scanning microscopy (CLSM) and image analysis.Without irrigation, the ZCD following drilling for two seconds was 135 ± 15 μm and this increased (fourfold, P 0.001) with five seconds of drilling. Irrigation reduced the ZCD following drilling for both two and five seconds (P 0.05, P 0.001 respectively) to the same level (approx. 60 μm). Without irrigation, drill bit and cartilage temperature increased rapidly to265 and 119 °C respectively, whereas the camera saturated at282 °C during drilling for five seconds. With irrigation, the drill bit temperature was significantly reduced during drilling for two and five seconds (approx. 90 °C) with negligible change in cartilage temperature. Drilling while irrigating with hyperosmotic saline (600 mOsm) reduced (P 0.01) the ZCD compared to saline, whereas chondrocyte death was increased (P 0.01) by Ca(2+) saline (5 mM).Reducing temperature during drilling by irrigation markedly suppressed, but did not abolish chondrocyte death. Optimising the irrigation solution by raising osmolarity and reducing Ca(2+) content significantly reduced chondrocyte death during drilling and may be clinically beneficial.

➤ Novel (i.e., quantitative and semiquantitative) cartilage imaging techniques can evaluate cartilage composition to augment information obtained from traditional magnetic resonance imaging sequences that detail morphology.➤ A well-defined role for drugs leading to chondroprotection has not yet been determined.➤ Shortcomings of bone marrow stimulation include limited production of hyaline repair tissue, unpredictable repair cartilage volume, and a negative impact on later cellular transplantation if required.➤ The role of biological augments, such as cellular concentrates or platelet-rich plasma, remains undefined. When their use is reported in the literature, it is important that their process of production and characterization be detailed.➤ Rehabilitation programs, incorporating controlled exercise and progressive partial weight-bearing, are an important part of cartilage repair surgery and should be detailed in reports on operative techniques applied.➤ Malalignment, meniscal injury, and ligament deficiency should be corrected in a staged or concomitant fashion to reduce the overall likelihood of mechanical failure in cartilage repair surgery.

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. There is no cure for OA, and no effective treatments which arrest or slow its progression. Current pharmacologic treatments such as analgesics may improve pain relief but do not alter OA disease progression. Prolonged consumption of these drugs can result in severe adverse effects. Given the nature of OA, life-long treatment will likely be required to arrest or slow its progression. Consequently, there is an urgent need for OA disease-modifying therapies which also improve symptoms and are safe for clinical use over long periods of time. Nutraceuticals—food or food products that provide medical or health benefits, including the prevention and/or treatment of a disease—offer not only favorable safety profiles, but may exert disease- and symptom-modification effects in OA. Forty-seven percent of OA patients use alternative medications, including nutraceuticals. This review will overview the efficacy and mechanism of action of commonly used nutraceuticals, discuss recent experimental and clinical data on the effects of select nutraceuticals, such as phytoflavonoids, polyphenols, and bioflavonoids on OA, and highlight their known molecular actions and limitations of their current use. We will conclude with a proposed novel nutraceutical-based molecular targeting strategy for chondroprotection and OA treatment.

Cartilage injuries of the knee are common and can be managed in a variety of ways. Choice of management must take into account the demands and expectations of the patient as well as the size, depth and location of the defect, how chronic it is and any concomitant intra-articular, extra-articular or general conditions. Previous treatments and injuries should be addressed before starting the treatment. Defect size is one of the most important parameters to take into account for pre-operative planning. All symptomatic cartilage defects of type III or IV using the International Cartilage Repair Society grading system should be managed surgically. No more than three localized cartilage defects can be treated successfully at the same time. Cartilage lesions can be managed with a wide spectrum of different techniques that can be used isolated or in combination according to surgeon’s choice. These techniques can be classified into five main groups: (1) cartilage reparative techniques (microfracture, drilling, cartilage shaving), (2) cartilage restoration techniques (fresh allograft transplantation or autograft transplantation – mosaicplasty), (3) autologous chondrocyte implantation (ACI) or matrix-induced autologous chondrocyte implantation (MACI), (4) other biologic approaches, including repair with gene-activated matrices (GAMs), scaffolds, mesenchymal stem cell (MSCs), platelet-rich plasma (PRP), growing factors (GRs), magnetically labelled synovium-derived cells (M-SDCs), bone morphogenetic proteins (BMPs) and elastic-like polypeptide gels, and (5) other therapies such as osteotomies, stem cell-coated titanium implants and chondroprotection with pulsed electromagnetic fields (PEMFs).

Resumen El manejo de la artrosis (OA) constituye un importante reto. La mayoria de las recomendaciones publicadas van dirigidas a controlar los sintomas de la OA, es decir, reducir el dolor y mejorar la funcion articular. Sin embargo, el principal objetivo a alcanzar en el tratamiento de la OA seria retrasar o detener la progresion de la enfermedad. En funcion de este objetivo, las diferentes terapias deben ayudar a preservar la integridad de la articulacion a traves del control de la degradacion del cartilago, la inflamacion sinovial y la esclerosis del hueso subcondral, los 3 tejidos involucrados en la fisiopatologia de la OA. Esto debe tenerse en cuenta tanto para el desarrollo de futuros tratamientos como para los farmacos disponibles actualmente. El condroitin sulfato (CS) forma parte de los denominados SYSADOA (del ingles symptomatic slow acting drugs for osteoarthritis) que define a un grupo de farmacos de accion lenta para el tratamiento sintomatico de la OA. Existe, sin embargo, un cuerpo de evidencia creciente que demuestra su efecto DMOAD (del ingles disease modifying osteoarthritis drugs), es decir, farmacos de accion lenta para la OA capaces de modificar la estructura. Esta revision tiene por objeto recopilar y sintetizar la informacion acerca del efecto protector que el CS ejerce sobre el cartilago, asi como su capacidad de preservar las cualidades del hueso subcondral.

Objetivo Evaluar la eficacia y seguridad de una unica inyeccion intraarticular de acido hialuronico (AH)+manitol en artrosis de rodilla (AR). Material y metodo Estudio prospectivo, abierto, no-comparativo con 80 pacientes diagnosticados de AR, de los cuales 79 finalizaron el estudio. Recibieron una inyeccion intraarticular de 2ml de AH al 2%+manitol al 0,5% (dia 0) y fueron monitorizados durante 6 meses. Los dias 0, 15, 30, 60, 90, 120, 150 y 180 se evaluaron dolor y funcionalidad articular mediante una escala analogica visual (EAV) y el indice WOMAC, eficacia y seguridad segun medico y paciente, y medicacion de rescate como medida indirecta del dolor. Resultados Disminucion significativa del dolor articular, rigidez e incapacidad funcional en comparacion con el valor inicial en todas las visitas (p

Osteoarthritis (osteoarthrosis) is a dege­ne­ra­tive disease of articular cartilage, and for its therapy we should usually use non-steroidal anti-inflammatory drugs. In the present review it was shown that one of these drugs — nimesulide — additionally to anti-inflammatory activity as a result of preferential inhibition of cyclooxygenase-2 has also chondroprotective effect due to in­hi­bi­tion of lipid peroxydation, decreasing of the level and activity of matrix metalloproteinases and inhibition of chondrocyte apoptosis in the cartilage tissue. Combination of anti-inflammatory and chondroprotective activity pro­du­ces more benefit effect on cartilage degeneration in a case of osteoarthritis., Остеоартрит (остеоартроз) представляет собой дегенеративное заболевание сус­тавного хряща, и для его терапии часто применяют нестероидные противовоспалительные средства. В рамках настоящего обзора было показано, что один из таких препаратов — ни­ме­сулид в дополнение к противовоспалительным свойствам, связанным с преимущественным ингибированием циклооксигеназы 2-го типа, проявляет также хондропротективное действие, которое реализуется за счет угнетения перекисного окисления липидов, снижения содержания и активности матриксных металлопротеиназ и торможения апоптоза хондроцитов в хрящевой ткани. Сочетание противовоспалительного и хондропротективного действия позволяет более эффективно бороться с дегенерацией хряща при остеоартрите., Остеоартрит (остеоартроз) являє собою дегенеративне захворювання суглобового хряща, і для його терапії часто використовують нестероїдні протизапальні засоби. У рамках даного обзору було показано, що один із таких препаратів — німесулід на додаток до протизапальних властивостей, що пов’язані з переважним інгібуванням циклооксигенази 2-го типу, справляє також хондропротективну дію, яка реалізується через пригнічення перекисного окислення ліпідів, зниження вмісту та активності матриксних металопротеїназ і гальмування апоптозу хондроцитів хрящової тканини. Поєднання протизапальної та хондропротективної дії дозволяє більш ефективно боротися з дегенерацією хряща при остеоартриті.

At the beginning of the new millennium, there was a breakthrough in platelet-rich plasma (PRP) therapy for tissue repair. The mechanisms governing the effects of this therapy in joint pathology remain largely unexplored.This review is primarily based on PubMed and Web of Knowledge searches with the terms osteoarthritis in combination with PRP, treatment, cartilage, synovium, platelets, inflammation and/or angiogenesis. This search was completed by a manual search for relevant studies. We mainly include papers from the last 5 years. The concept of dynamic reciprocity is used to shape understanding of the spatial relationship between cells and their microenvironments as well as between tissues within the joint. We describe the processes of joint injury and pathology relevant to the mechanism of action of PRP, and elaborate insights into how PRP components may influence inflammation, angiogenesis, cell death and cartilage chondroprotection.PRP therapies are more complicated than previously acknowledged, and an understanding of the fundamental processes and pivotal molecules involved will hopefully be elucidated soon. This challenge is to provide a comprehensive description of the relationship between PRP components, healing mechanisms and clinical outcomes. Although PRP therapies in clinical trials await assessment, they have shed light on new avenues of management because of their effects on repair functions.

Objective: Articular cartilage injury is common after athletic injury and remains a difficult treatment conundrum both for the surgeon and athlete. Although recent treatments for damage to articular cartilage have been successful in alleviating symptoms, more durable and complete, long-term articular surface restoration remains the unattained goal. In this article, we look at both new ways to prevent damage to articular surfaces as well as new techniques to recreate biomechanically sound and biochemically true articular surfaces once an athlete injures this surface. This goal should include reproducing hyaline cartilage with a well-integrated and flexible subchondral base and the normal zonal variability in the articular matrix. Results: A number of nonoperative interventions have shown early promise in mitigating cartilage symptoms and in preclinical studies have shown evidence of chondroprotection. These include the use of glucosamine, chondroitin, and other neutraceuticals, viscosupplementation with hyaluronic acid, platelet-rich plasma, and pulsed electromagnetic fields. Newer surgical techniques, some already in clinical study, and others on the horizon offer opportunities to improve the surgical restoration of the hyaline matrix often disrupted in athletic injury. These include new scaffolds, single-stage cell techniques, the use of mesenchymal stem cells, and gene therapy. Conclusion: Although many of these treatments are in the preclinical and early clinical study phase, they offer the promise of better options to mitigate the sequelae of athletically induced cartilage.

Objectives. To compare the ability of different cyclodextrin polysulphate (CDPS) derivatives to affect human articular cartilage cell metabolism in vitro. Methods. OA chondrocytes were cultured in alginate and exposed to 5 µg/ml of 2,3,6-tri-O-methyl-β-cyclodextrin (ME-CD), 2,3-di-O-methyl-6-sulphate-β-cyclodextrin (ME-CD-6-S), 2,6-di-O-methyl-3-sulphate-β-cyclodextrin (ME-CD-3-S), (2-carboxyethyl)-β-CDPS (CE-CDPS), (2-hydroxypropyl)-β-CDPS (HP-CDPS), 6-monoamino-6-monodeoxy-β-CDPS (MA-CDPS) or β-CDPS for 5 days. Effects on IL-1-driven chondrocyte extracellular matrix (ECM) metabolism were assayed by analysis of the accumulation of aggrecan in the interterritorial matrix, IL-6 secretion and qPCR. MA-CDPS, HP-CDPS, CE-CDPS and CDPS were analysed for their in vitro effect on coagulation and their ability to activate platelets in an in vitro assay to detect possible cross-reactivity with heparin-induced thrombocytopenia (HIT) antibodies. Results. The monosulphated cyclodextrins ME-CD-6-S and -3-S failed to affect aggrecan synthesis and IL-6 secretion by the OA chondrocytes. Polysulphated cyclodextrins MA-CDPS, HP-CDPS, CE-CDPS and CDPS at 5 µg/ml concentrations, on the other hand, significantly induced aggrecan production and repressed IL-6 release by the chondrocytes in culture. aPTT and PT for all derivatives were lengthened for polysaccharide concentrations >50 µg/ml. Five micrograms per millilitre of β-CDPS concentrations that significantly modulated ECM ground substance production in vitro did not affect aPTT or PT. Furthermore, CE-CDPS, in contrast to MA-CDPS, HP-CDPS and CDPS, did not significantly activate platelets, suggesting a minimal potential to induce HIT thromboembolic accidents in vivo. Conclusions. CE-CDPS is a new, structurally adjusted, sulphated β-cyclodextrin derivative with preserved chondroprotective capacity and a promising safety profile.

Large meniscal defects are a common problem for which treatment options are limited. Successful meniscal regeneration has been achieved by using grafts of small intestinal submucosa in posterior, vascular meniscal defects in a dog model. This study investigates the long-term effects of a tibial tunnel fixation technique and a clinically based meniscectomy defect on meniscal regeneration using this model. Eight mongrel dogs underwent medial arthrotomy and partial meniscectomy. The dogs were divided into groups based on defect treatment: small intestinal submucosa (n = 4) or meniscectomy (n = 4). Dogs were scored for lameness by subjective scoring postoperatively, sacrificed at 6 months, and assessed for articular cartilage damage, gross and histologic appearance of the operated meniscus, amount of new tissue in the defect, and relative compressive stiffness of articular cartilage. Dogs in the meniscectomy group were significantly (P = .002) more lame than dogs treated with small intestinal submucosa. Small intestinal submucosa-treated joints had significantly (P = .01) less articular cartilage damage than meniscectomy joints. Small intestinal submucosa meniscal implants resulted in production of meniscal-like replacement tissue, which was consistently superior to meniscectomy in amount, type, and integration of new tissue, chondroprotection, and limb function during the study period. Small intestinal submucosa implants may be useful for treatment of large posterior vascular meniscal defects in humans. The tibial tunnel technique used for fixation may have clinical advantages and therefore warrants further investigation.

Kayo Masuko1, Minako Murata2, Kazuo Yudoh2, Tomohiro Kato1, Hiroshi Nakamura31Department of Biochemistry; 2Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki-shi, Kanagawa, Japan; 3Department of Joint Disease and Rheumatism, Nippon Medical School, Bunkyo-ku, Tokyo, JapanAbstract: Hyaluronic acid (HA) has been widely used for viscosupplementation of diseased or aged articular joints. However, recent investigations have revealed the active anti-inflammatory or chondroprotective effect of HA, suggesting its potential role in attenuation of joint damage. In particular, interactions between HA and other inflammatory mediators are attracting interest. This review summarizes several aspects of recent investigations of the anti-inflammatory effects of HA in arthritis.Keywords: hyaluronan, inflammation, chondroprotection

It has been demonstrated that pulsed electromagnetic field (PEMF) stimulation has a chondroprotective effect on osteoarthritis (OA) progression in the knee joints of the 12-month-old guinea pigs. The aim of the present study was to discover whether the therapeutic efficacy of PEMFs was maintained in older animals also in more severe OA lesions. PEMFs were administered daily (6 h/day for 6 months) to 15-month-old guinea pigs. The knee joints (medial and lateral tibial plateaus, medial and lateral femoral condyles) were evaluated by means of a histological/histochemical Mankin modified by Carlsson grading score and histomorphometric measurements of cartilage thickness (CT), fibrillation index (FI), subchondral bone thickness (SBT) and epiphyseal bone microarchitecture (bone volume: BV/TV; trabecular thickness: Tb.Th; trabecular number: Tb.N; trabecular separation: Tb.SP). Periarticular knee bone was also evaluated with dual X-ray absorptiometry (DXA). PEMF stimulation significantly changed the progression of OA lesions in all examined knee areas. In the most affected area of the knee joint (medial tibial plateau), significant lower histochemical score (p

The paper presents a review of current trends in biotribiology. The authors discuss the extent of the achievements in this field at the turn of the 21st century. This period is distinguished by the discovery of liquid-crystalline and quasi-electret states revealed by AFM in the articular lubricating fluid; new boundary lubrication mechanisms, which are realized by organic super-lubricants at the nanolevel; and methods for in vitro study of friction in joints using electromagnetic fields able to simulate the natural articular biofield. A relationship is traced between biotribology and the chief directions in contemporary orthopedics, namely: 1) articular chondroprotection exercised via local therapeutic methods based on tribomonitoring of pharmaceutic substances; 2) injection of drugs based on blood serum; 3) development of a new generation of articular endoprostheses able to simulate the biophysical properties of synovial joints. It is shown that progress in modern biotribology has provided scientific substantiatiation of orthopedic treatment procedures. The ideas advanced by I.V. Kragelskii in resolving various engineering problems have proven fruitful in biotribology, which deals with living tissues and biological fluids.

Meniscal scaffolds represent an attractive surgical option for irreparable meniscal lesions in appropriately symptomatic patients. Although a wide range of conditions could be potentially treated, good results are strictly dependent upon adherence to proper surgical indications. Scaffold implant could be performed only in case of partial medial or lateral meniscal defect with intact meniscal horns. The arthroscopic implantation is technically challenging where traditional surgical risks are present; however, good to excellent results have been reported ranging from 70 to 90 %. Both CMI® and Actifit® have been reported to undergo reabsorption and substitution over time, with a meniscus-like tissue with the potential of chondroprotection, good integration with the native meniscus, and no cartilage damage.

Joint injuries are common, especially among young adults aged 18 to 44 years. They are accompanied by a cascade of events that increase the risk of posttraumatic osteoarthritis (PTOA). Therefore, understanding of biological responses that predispose to PTOA should help in determining treatment modalities to delay and/or prevent the onset and progression of the disease. The vast majority of the literature pointed to chondrocyte death and apoptosis, inflammation and matrix damage/fragmentation being the earliest events that follow joint trauma. Together these events lead to the development of osteoarthritis-like focal cartilage lesions that if untreated have a tendency to expand and progress to fully developed disease. Currently, the only treatments available for joint trauma are surgical interventions. Experimental biologic approaches involve engineering of cartilage with the use of cells (stem cells or chondrocytes), juvenile or adult cartilage pieces, scaffolds, and various polymeric matrices. The major challenge for all of them is regeneration of normal functional mature hyaline cartilage that can sustain the load, resist compression, and most important, integrate with the host tissue. If the tissue is spontaneously repaired it fails to reproduce original structure and function and thus, may be more susceptible to re-injury. Thus, there is a critical need to develop novel molecular mechanism-based therapeutic approaches to biologic chondral and/or osteochondral repair. The focus of this review is on the earliest molecular and cellular manifestations of injury that can be grouped based on the following therapeutic options for PTOA: chondroprotection, anti-inflammatory, matrix protection, and matrix remodeling/matrix synthesis.

Introduction Incidence of meniscal lesions is increasing in the pediatric population. Given the harmful impact of meniscectomy, meniscal repair is attempted whenever possible. The present study sought to assess the efficacy of FasT-Fix (Smith and Nephew) all-inside arthroscopic meniscal repair devices in childhood meniscal lesions. The study hypothesis was that functional results would be equivalent to those of other suture techniques. Material and methods Nineteen patients were assessed following arthroscopic meniscal repair, at a mean 6 years (range: 3–9 years). Mean age was 14.8 years. There was associated ACL tear in 31% of cases. Functional assessment used Lysholm, subjective IKDC, Tegner activity level and KOOS scores. Anatomic assessment of healing used MRI, arthroscopy or CT-arthrography. Results At last follow-up, the meniscal survival rate was 89.5% (n = 17/19). Functional results were good: Lysholm: 95.7/100; subjective IKDC: 90.7/100; Tegner: 7.64. Imaging found systematic healing. Discussion All-inside arthroscopic meniscal suture is increasingly used in adults, and can also be implemented in children or adolescents in pediatrics. FasT-Fix (Smith and Nephew) implants, although not always easy to use, ensure a perfectly functional knee and conserve long-term meniscal chondroprotection with a low risk of complications. Level of evidence IV, retrospective study.

Many compounds are being investigated for the control of symptoms of osteoarthritis in people and animals. Ideally, treatment should include analgesia, inflammation control, and chondroprotection. With further progress in this area, combination therapies tailored to the needs of the individual animal should enable us to maximize efficacy and minimize side effects. Only a few of the newer therapies and pharmaceutic agents have been investigated in the horse, however. With more rigorous investigation, they may be determined to be ineffective or unsafe. Meanwhile, as much information should be gathered from manufacturers as possible so as to ensure that appropriate recommendations are made.

Summary Objective Articular cartilage may experience iatrogenic injury during routine orthopaedic/arthroscopic procedures. This could cause chondrocyte death, leading to cartilage degeneration and posttraumatic osteoarthritis. In an in vitro cartilage injury model, chondrocyte death was reduced by increasing the osmolarity of normal saline (NS), the most commonly-used irrigation solution. Here, we studied the effect of hyperosmolar saline (HS) on chondrocyte viability and cartilage repair in an in vivo injury model. Design Cartilage injury was induced by a single scalpel cut along the patellar groove of 8 week old rats in the absence of irrigation or with either NS (300 mOsm) or HS (600 mOsm). The percentage of cell death (PCD) within the injured area was assessed using confocal microscopy. Repair from injury was evaluated by histology/immunostaining, and inflammatory response by histology, cytokine array analysis and ELISA (enzyme-linked immunosorbent assay). Results The PCD in saline-irrigated joints was increased compared to non-irrigated (NI) joints [PCD = 20.8% (95%CI; 14.5, 27.1); PCD = 9.14% (95%CI; 6.3, 11.9); P = 0.0017]. However, hyperosmotic saline reduced chondrocyte death compared to NS (PCD = 10.4% (95%CI; 8.5, 12.3) P = 0.0024). Repair score, type II collagen and aggrecan levels, and injury width, were significantly improved with hyperosmotic compared to NS. Mild synovitis and similar changes in serum cytokine profile occurred in all operated joints irrespective of experimental group. Conclusions Hyperosmotic saline significantly reduced the chondrocyte death associated with scalpel-induced injury and enhanced cartilage repair. This irrigation solution might be useful as a simple chondroprotective strategy and may also reduce unintentional cartilage injury during articular reconstructive surgery and promote integrative cartilage repair, thereby reducing the risk of posttraumatic osteoarthritis.

Preclinical studies have shown that I-ONE therapy controls inflammation, protects cartilage and favours chondrocytes’ metabolic activity. Prospective, randomized and double-blind studies have shown that IONE therapy enhances patients’ functional recovery and controls local pain due to the inflammatory reaction elicited by the arthroscopic treatment. I-ONE therapy is without side effects, induces an effective chondroprotection, it is indicated immediately after knee surgery and has positive long term effects.

Systematic review of overlapping meta-analyses shows that platelet-rich plasma improves knee pain and function in patients with knee osteoarthritis. Ultimately, biologics hold promise for chondroprotection in addition to symptomatic relief.

The combination of anterior cruciate ligament (ACL) reconstruction and meniscal allograft transplantation (MAT) may produce a synergistic effect for chondroprotection and knee stability. The menisci have an important role in knee stability via load-sharing with the ACL. This role may be particularly relevant in the setting of revision ACL reconstruction, as meniscus loss is often present and can lead to increased strain on an ACL graft. Since the failure rates are generally higher in revision ACL surgery compared to primary reconstruction, careful consideration of meniscus status is prudent. A thorough preoperative history, physical examination, and radiographic evaluation should be performed to ascertain the contributors to ACL reconstruction failure. Careful patient selection and counseling regarding the potential long-term patient outcome including increased risk for arthrosis should be performed. Young patients with ACL and meniscal deficiency and minimal chondral injury represent a unique situation in which MAT and ACL reconstruction can be extremely beneficial. Consideration of these factors is crucial for optimizing the outcome following revision ACL reconstruction.

Cartilage therapy for focal articular lesions of the knee has been implemented for more than a decade, and it is becoming increasingly available. What do we know on the healing response of cartilage lesions? What do we know on the treatment of focal cartilage lesions of the knee and the prognostic factors involved? PubMed articles related to articular cartilage regeneration of the knee in clinical studies were searched from January 2006 to November 2012, using the following key words: articular cartilage, regeneration, clinical studies, and knee. A total of 44 reports were found. They showed the following possibilities for the treatment of focal lesions of the articular cartilage of the knee: cartilage regeneration and repair including cartilage reparation with gene-activated matrices, autologous chondrocyte implantation (ACI) and matrix-induced ACI (MACI), microfracture, osteochondral autograft transfer (mosaicplasty), biological approaches (scaffolds, mesenchymal stem cells-MSCs, platelet-rich plasma, growing factors-GF, bone morphogenetic proteins-BMPs, magnetically labeled synovium-derived cells-M-SDCs, and elastic-like polypeptide gels), osteotomies, stem-cell-coated titanium implants, and chondroprotection with pulsed electromagnetic fields. Untreated cartilage lesions on the femoral condyles had a superior healing response compared to those on the tibial plateaus, and in the patellofemoral joint. Clinical outcome regarding the treatment of medial defects is better than that of the lateral defects. Improvement from baseline was better for patientsor = 30 years compared with patientsor = 30 years. ACI, MACI, and mosaicplasty have shown similar results. The results of comparative clinical studies using ACI have shown some superiority over conventional microfracturing in medium or large defects and in long-term durability. Some biological methods such as scaffolds, MSCs, GF, M-SDCs, BMPs, and elastic-like polypeptide gels still need more research.