Experimental Osteoarthritis Research Articles

Макроскопічні зміни колінного суглобу при внутрішньосуглобовому та внутрішньом’язовому введенні хондроїтину сульфату на тлі експериментального остеоартрозу

The purpose of the study was to investigate macroscopic changes in the knee joint during intraarticular and intramuscular administration of chondroitin sulfate to laboratory rabbits in experimental osteoarthritis. Materials and methods. Experimental studies were performed on nonlinear, healthy 16 adult Chinchilla rabbits (8 males and 8 females) weighing 2.5 kg. The experimental model of osteoarthritis was based on the introduction of a solution of monoiodoacetic acid into the knee joint at the rate of 3 mg per 50 μl of sterile saline. Chondroitin sulfate was administered intraarticularly and intramuscularly. Chondroitin sulfate was administrated intraarticularly 0.24 ml 1 time in 3 days 5 times on 28, 31, 34, 37 and 40 days of the experiment and intramuscularly – 0.24 ml 1 time per day every other day for 25 days (from the 28th day of the experiment to the 53rd day). The analysis of macroscopic assessment of rabbit knee joints was performed. Results and discussion. Intramuscular and intraarticular injection of chondroitin sulfate reduces the intensity of the degenerative-dystrophic process due to the impact on inflammatory and the activation of anabolic mechanisms. Intraarticular administration of chondroitin sulfate leads to a greater increase in the level of factors of bone and cartilage formation and a greater decrease in the levels of factors of the acute phase of inflammation and factors that destroy the cartilage matrix. In our study, we attempted to visualize and compare morphological changes in intraarticular and intramuscular administration of chondroitin sulfate on the background of experimental osteoarthritis. The study highlights the possibility of using chondroitin sulfate in intraarticular administration, identified the effectiveness and impact on macroscopic changes in the tissues of the knee joint, assessed differences from intramuscular use in experimental osteoarthritis. However, in view of our research, it is not necessary to claim that all chondroitin sulfate drugs will have a similar effect. It should be remembered that the effectiveness of chondroitin sulfate depends on many factors, including the quality of raw materials. Conclusion. Intramuscular administration of chondroitin sulfate revealed a lower intensity of destructive changes in the cartilaginous surface of the knee joint, and intraarticular – the absence of cartilage destruction and defects of the cartilaginous surface, which indicates the peculiarity of the topical effect of the chondroitin sulfate

Characterization of rhodanine derivatives as potential disease-modifying drugs for experimental mouse osteoarthritis

This study was performed to characterize selected rhodanine derivatives as potential preclinical disease-modifying drugs for experimental osteoarthritis (OA) in mice. Three rhodanine derivatives, designated rhodanine (R)-501, R-502, and R-503, were selected as candidate OA disease-modifying drugs. Their effects were evaluated by intra-articular (IA) injection in OA mouse models induced by DMM (destabilization of the medial meniscus) or adenoviral overexpression in joint tissues of hypoxia-inducible factor (HIF)-2α or zinc importer ZIP8. The regulatory mechanisms impacted by the rhodanine derivatives were examined in primary-culture chondrocytes and fibroblast-like synoviocytes (FLS). All three rhodanine derivatives inhibited OA development caused by DMM or overexpression of HIF-2α or ZIP8. Compared to vehicle-treated group, for example, IA injection of R-501 in DMM-operated mice reduced median OARSI grade from 3.78 (IQR 3.00-5.00) to 1.89 (IQR 0.94-2.00, P=0.0001). R-502 and R-503 also reduced from 3.67 (IQR 2.11-4.56) to 2.00 (IQR 1.00-2.00, P=0.0030) and 2.00 (IQR 1.83-2.67, P=0.0378), respectively. Mechanistically, the rhodanine derivatives inhibited the nuclear localization and transcriptional activity of HIF-2α in chondrocytes and FLS. They did not bind to Zn2+ or modulate Zn2+ homeostasis in chondrocytes or FLS; instead, they inhibited the nuclear localization and transcriptional activity of the Zn2+-dependent transcription factor, MTF1. HIF-2α, ZIP8, and interleukin-1β could upregulate matrix-degrading enzymes in chondrocytes and FLS, and the rhodanine derivatives inhibited these effects. IA administration of rhodanine derivatives significantly reduced OA pathogenesis in various mouse models, demonstrating that these derivatives have disease-modifying therapeutic potential against OA pathogenesis.

RAPAMYCIN DELAYS BONE-RELATED HALLMARKS OF OSTEOARTHRITIS IN THE COMMON MARMOSET: PRELIMINARY FINDINGS OF AN ONGOING LIFESPAN STUDY

Purpose: Increased mechanistic target of rapamycin (mTOR) activity is seen in cartilage from human osteoarthritis (OA) patients and is sufficient to induce OA in mice. Rapamycin, a small molecule inhibitor of mTOR, extends lifespan in multiple species and protects against experimental OA in mice. However, it remains unknown if rapamycin can modify features of naturally occurring OA in non-human primates. Therefore, we analyzed the knee joints of common marmosets receiving rapamycin during an ongoing lifespan study.

AUTOMATIC DETECTION OF OSTEOPHYTES FROM CONTRAST ENHANCED μCT-IMAGED RAT TIBIAS USING STATISTICAL SHAPE MODELS

Purpose: Osteophyte (OsP) formation is an important feature of osteoarthritis (OA). Better tools to study OsP formation in detail can yield important insight into OA progression and aid in phenotyping the disease more accurately. Identifying OsPs, as well as their precursors, in pre-clinical OA models is especially important when studying early OA and disease modifying treatments using animal models. OsPs may develop prior to articular cartilage degeneration and their development can be especially rapid in experimental OA models with artificially induced OA.

Effects of Pulsed Ultrasound on Knee Joint Friction and Inflammation in Non-traumatic Experimental Osteoarthritis

Introduction: Knee Osteoarthritis (OA) is one of the most important etiologies of pain and disability among adults. The effects of pulsed Ultrasound (US) on pain reduction and joint function have been proven, but its role on joint friction and inflammatory mediators is still unclear. Therefore, this study was designed to investigate the effects of US on knee joint friction and inflammation in non-traumatic experimental knee OA. Materials and Methods: Forty-eight guinea pigs were randomly assigned into four groups: OA+US, OA+US sham, 30 days after OA induction (OA30), and normal control (n=12 for each group). OA was induced by intra-articular injection of 3 mg/kg of Mono-Iodoacetate (MIA) in the animal’s left knee. Joint circumstance and weight of the animals were measured at baseline, before (i.e., after 30 days of MIA injection), and after US treatment. Joint friction was evaluated by a pendulum friction tester system. Cytokine levels, including Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-1β, were measured by the ELISA method. The Pearson correlation coefficient was calculated to study the relationships between friction and inflammation variables. Results: Joint circumference was increased in the OA30 group. Joint friction variables, including exponential curve fitting, cycle number, and friction coefficient, were significantly better in the US group (P<0.05). TNF-α and IL-1β cytokine levels were significantly lower in the US group. A significant positive correlation was observed between joint friction indices and TNF-α and IL-1β cytokine levels (P<0.05). Conclusion: US was an effective approach for reducing joint friction and inflammation in OA30. Moreover, the relationship between knee joint friction and inflammation could help us better understand the etiology, mechanism, and treatment strategies of this disease.

Bone and cartilage condition in experimental osteoarthritis and hypothyroidism.

Aim To investigate changes in bone and cartilage tissue during the use of non-steroidal anti-inflammatory drugs and paracetamol in experimental osteoarthritis and hypothyroidism by the markers CTX-I and CTX-II. Methods The experiments were performed on 75 white nonlinear rats of both sexes, which recreated osteoarthritis and hypothyroidism. Experimental osteoarthritis was performed by single intra-articular administration of monoiodoacetic acid solution in the knee joint and experimental hypothyroidism was reconstructed by enteral administration of a solution of carbimazole. After the formation of the experimental models on the 42nd day of the experiment, the animals were divided into 14 groups and drug administration began daily for 5 days. The quantitative level of markers of blood serum was performed by specific kits, which are based on ELISA on 42 and 47 days of the experiment. Results The degree of influence on degenerative-dystrophic processes in bone tissue, which was assessed by the level of the marker СTX-I in the serum of rats, the studied drugs were as follows: diclofenac sodium > ibuprofen > nimesulide = meloxicam > celecoxib > paracetamol. According to the degree of influence on degenerative-dystrophic processes in cartilage tissue, which were assessed by the level of marker СTX-II in the serum of rats, the studied drugs were as follows: nimesulide > celecoxib > meloxicam > ibuprofen > diclofenac sodium > paracetamol. Conclusion Determination of the levels of CTX I and СTX II allows the evaluation of the bone and cartilage condition in experimental osteoarthritis and hypothyroidism.

Eldecalcitol regulates the gene expressions of articular cartilage markers and differentiation markers in chondrocytes

Vitamin D has been shown to reduce symptoms in patients with osteoarthritis (OA). In a previous study, local administration of eldecalcitol, an active vitamin D3 analog, reduced degenerative changes in articular cartilage in the early phase of experimental OA. However, the target of vitamin D in OA remains unknown. Here, we investigated the effect of eldecalcitol treatment on chondrocytes, which were divided into superficial zone chondrocytes (SZC), deep zone chondrocytes (DZC), and differentiated chondrocytes. SZC and DZC were cultured in monolayer and 3D pellet cultures treated with eldecalcitol. The gene expressions of articular cartilage and chondrocyte differentiation markers were evaluated. Histological analysis of SZC and DZC 3D pellet cultures was performed. The results showed that the articular cartilage markers ETS-related gene (Erg) and lubricin/proteoglycan 4 (PRG4) were significantly increased in SZC, but not in DZC, in the monolayer culture treated with eldecalcitol. The chondrocyte differentiation markers type X collagen and alkaline phosphatase (ALP) were significantly decreased in the DZC pellet culture treated with eldecalcitol. Immunochemical analysis also showed that Erg and lubricin/PRG4 expressions were elevated in the SZC pellet culture treated with eldecalcitol, while type X collagen and ALP expressions were decreased in the DZC pellet culture treated with eldecalcitol. In conclusion, this study showed that eldecalcitol upregulated articular cartilage markers in SZC and suppressed differentiation markers in DZC. Such regulation of chondrocytes by eldecalcitol could be potentially effective against OA progression.

Mechanical overloading promotes chondrocyte senescence and osteoarthritis development through downregulating FBXW7

ObjectivesTo investigate the role of mechanical stress in cartilage ageing and identify the mechanistic association during osteoarthritis (OA) progression.MethodsF-box and WD repeat domain containing 7 (FBXW7) ubiquitin ligase expression and...

Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx

IntroductionsExcessive mechanical stress is closely associated with cell death in various conditions. Exposure of chondrocytes to excessive mechanical loading leads to a catabolic response as well as exaggerated cell death. Ferroptosis is a recently identified form of cell death during cell aging and degeneration. However, it's potential association with mechanical stress remains to be illustrated. ObjectivesTo identify whether excessive mechanical stress can cause ferroptosis. To explore the role of mechanical overloading in chondrocyte ferroptosis. MethodsChondrocytes were collected from loading and unloading zones of cartilage in patients with osteoarthritis (OA), and the ferroptosis phenotype was analyzed through transmission electron microscope and microarray. Moreover, the relationship between ferroptosis and OA was analyzed by GPX4-conditional knockout (Col2a1-CreERT: GPX4flox/flox) mice OA model and chondrocytes cultured with high strain mechanical stress. Furthermore, the role of Piezo1 ion channel in chondrocyte ferroptosis and OA development was explored by using its inhibitor (GsMTx4) and agonist (Yoda1). Additionally, chondrocyte was cultured in calcium-free medium with mechanical stress, and ferroptosis phenotype was tested. ResultsHuman cartilage and mouse chondrocyte experiments revealed that mechanical overloading can induce GPX4-associated ferroptosis. Conditional knockout of GPX4 in cartilage aggravated experimental OA process, while additional treatment with ferroptosis suppressor protein (FSP-1) and coenzyme Q10 (CoQ10) abated OA development in GPX4-CKO mice. In mouse OA model and chondrocyte experiments, inhibition of Piezo1 channel activity increased GPX4 expression, attenuated ferroptosis phenotype and reduced the severity of osteoarthritis. Additionally, high strain mechanical stress induced ferroptosis damage in chondrocyte was largely abolished by blocking calcium influx through calcium-free medium. ConclusionsOur findings show that mechanical overloading induces ferroptosis through Piezo1 activation and subsequent calcium influx in chondrocytes, which might provide a potential target for OA treatment.

THE EFFECT OF PELOID THERAPY ON THE DYNAMICS OF BIOCHEMICAL BLOOD PARAMETERS WITH EXPERIMENTAL OSTEOARTHRITIS

Formulation of the problem. It is known that until recently, complex conservative therapy remained the leading method in the treatment and medical rehabilitation of patients with osteoarthritis. Physical factors, both preformed and natural, occupy an important place in the therapy of patients with osteoarthritis. Analysis of recent research and publications. The most popular among the means used in the treatment of patients with osteoarthritis of the knee joints are therapeutic muds. According to modern ideas, their therapeutic action is based on a combination of mechanical, thermal, chemical, biological and other components of the peloid. Formulation of the purpose of the article. To study the effect of peloid therapy on biochemical blood parameters of white rats with experimental osteoarthritis. Presenting main material. The content of glycoproteins in the blood of rats was probably increased on the 7th day in animals with osteoarthritis compared to the values in intact ones. A slight increase in the level of glycoproteins was maintained throughout the experiment until the 30th day. During the treatment with sulphide-mud mud, on the 7th day, an increase in the content of glycoproteins was noted to the level of the indicators of the control group. By the 15th day, the concentration of glycoproteins probably decreased compared to its value in the control group, however, by the end of the observations, the amount of glycoproteins in the blood serum of the experimental animals exceeded this indicator than in the rats of the control group. These data indicate that the use of sulphide mud reduces the activity of the inflammatory process, but not sufficiently. The concentration of chondroitin sulfates in the blood serum of experimental animals on the 7th and 15th day of osteoarthritis was increased in comparison with the results obtained in intact animals. However, by the 30th day, there was a decrease in the indicated indicator compared to the one that occurred earlier. Conclusions and prospects for further research. Thus, it was established that the use of peloidotherapy led to a decrease in the content of chondroitin sulfates in the blood serum of experimental animals in comparison with the corresponding term of the control group, which indicates the beneficial effect of peloidotherapy on the exchange of glycosaminoglycans. In the conditions of peloid therapy, the dynamics of biochemical indicators of the state of connective tissue were revealed, which indicated the beneficial effect of peloid applications on the knee joints of experimental rats, which was manifested in the reduction of the inflammatory and destructive process in the cartilage tissue of the affected joints. The prospect of further research is the application of this technique of pyeloid therapy in clinical orthopedic practice.

Intraarticular administration of chondroitin sulfate in experimental osteoarthritis

Introduction and aim. Osteoarthritis (OA) is generally a progressive disease that affects synovial joints, resulting in abnormalities to articular cartilage subchondral bone, synovium, and adjacent soft tissues. The purpose of this work was to investigate the specific activity of chondroitin sulfate (CS) in intra-articular and intramuscular administration to laboratory rabbits in experimental OA. Material and methods. OA was induced in rabbits by a single injection of mono-iodoacetate in knee joint. CS was administered intra-articularly and intramuscularly. The analysis of biochemical markers and macroscopic assessment of rabbit knee joints was performed. Results. Intramuscular and intra-articular injection of CS reduces the intensity of the degenerative-dystrophic process due to the impact on inflammatory and the activation of anabolic mechanisms. Intra-articular administration of CS leads to a greater increase in the level of factors of bone and cartilage formation and a greater decrease in the levels of factors of the acute phase of inflammation and factors that destroy the cartilage matrix. Conclusion. Intramuscular administration of CS revealed a lower intensity of destructive changes in the cartilaginous surface of the knee joint, and intramuscular – the absence of cartilage destruction and defects of the cartilaginous surface, which indicates the peculiarity of the topical effect of the CS.

Effects of Pulsed Ultrasound on Knee Joint Friction and Inflammation in Non-traumatic Experimental Osteoarthritis

Effects of Pulsed Ultrasound on Knee Joint Friction and Inflammation in Non-traumatic Experimental Osteoarthritis

Intra-articular Injection of Lornoxicam and MicroRNA-140 Co-loaded Cationic Liposomes Enhanced the Therapeutic Treatment of Experimental Osteoarthritis.

Osteoarthritis is a chronic joint disease characterized by chronic inflammation, progressive destruction of articular cartilage, and subchondral bone sclerosis. When compared to individual treatment, the combined administration of genes and small-molecule drugs for osteoarthritis may not only provide superior inflammation control and pain relief, but may also repair cartilage damage. Here, cationic liposomes (CL) were used to deliver small hydrophobic drugs and microRNA into chondrocytes to treat osteoarthritis. Lornoxicam cationic liposomes (Lnxc-CL) were prepared by film dispersion, and loaded with microRNA-140 (miR-140) by electrostatic interaction to obtain cationic liposomes co-loaded with lornoxicam and miR-140 (Lnxc-CL/miR-140). The prepared Lnxc-CL/miR-140 had a particle size of 286.6 ± 7.3nm, polydispersity index (PDI) of 0.261 ± 0.029 and zeta potential of 26.5 ± 0.5mV and protected miR-140 from RNase degradation for 24h. Lnxc-CL/miR-140 was evaluated for its ability to regulate gene expression in chondrocytes in vitro and to provide in vivo therapeutic effects for knee osteoarthritis in rats. The results of in vitro uptake experiments and polymerase chain reaction (PCR) analysis showed that Lnxc-CL/miR-140 efficiently delivered miR-140 into chondrocytes and up-regulated the expression of miR-140 and COL2A1 mRNA. Pharmacodynamics studies demonstrated that Lnxc-CL/miR-140 effectively treated osteoarthritis by eliminating joint inflammation and repairing damaged cartilage cells, with superior therapeutic effects compared to Lnxc or miR-140 alone. Overall, the findings of this study support the co-delivery of Lnxc and miR-140 with cationic liposomes as a potential new therapeutic strategy for the treatment of osteoarthritis.

A green-lipped mussel reduces pain behavior and chondrocyte inflammation and attenuated experimental osteoarthritis progression.

The green-lipped mussel (GLM) contains novel omega-3 polyunsaturated fatty acids, which exhibit anti-inflammatory and joint-protecting properties. Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage; oxidative stress plays a role in the pathogenesis of OA. The objectives of this study were to investigate the in vivo effects of the GLM on pain severity and cartilage degeneration using an experimental rat OA model, and to explore the mode of action of GLM. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) into the knee. Oral GLM was initiated on the day after 3dyas of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed both macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1β (IL-1β), IL-6, nitrotyrosine, and inducible nitric oxide synthase (iNOS) in knee joints. Also, the GLM was applied to OA chondrocyte, and the expression on catabolic marker and necroptosis factor were evaluated by real-time polymerase chain reaction. Administration of the GLM improved pain levels by preventing cartilage damage and inflammation. GLM significantly attenuated the expression levels of mRNAs encoding matrix metalloproteinase-3 (MMP-3), MMP-13, and ADAMTS5 in IL-1β-stimulated human OA chondrocytes. GLM decreased the expression levels of the necroptosis mediators RIPK1, RIPK3, and the mixed lineage kinase domain-like protein (MLKL) in IL-1β-stimulated human OA chondrocytes. Thus, GLM reduced pain and cartilage degeneration in rats with experimentally induced OA. The chondroprotective properties of GLM included suppression of oxidative damage and inhibition of catabolic factors implicated in the pathogenesis of OA cartilage damage. We suggest that GLM may usefully treat human OA.

Изучение структурных особенностей при экспериментальном хроническом остеоартрозе коленного сустава у кроликов

В статье описан собственный способ моделирования травматического остеоартроза коленного сустава у кроликов. Животным осуществляли доступ к суставу, пересекали большеберцовую связку, механическим путем проводили деструкцию центрального участка эпифизарной поверхности эпифиза большеберцовой кости, сосуды суставной сумки коагулировали по контуру сустава для создания дополнительной ишемизации. Гистологические исследования через 1,5 и 2,5 месяца после операции показали дегенеративные изменения гиалинового хряща, редукции толщины и клеточного состава хряща, инвазию кровеносных сосудов и формирование лакун в глубоких слоях хряща. Выявлены случаи полной (тотальной) дегенерации суставной поверхности.

Avenanthramide C as a novel candidate to alleviate osteoarthritic pathogenesis

Osteoarthritis (OA) is a degenerative disorder that can result in the loss of articular cartilage. No effective treatment against OA is currently available. Thus, interest in natural health products to relieve OA symptoms is increasing. However, their qualities such as efficacy, toxicity, and mechanism are poorly understood. In this study, we determined the efficacy of avenanthramide (Avn)-C extracted from oats as a promising candidate to prevent OA progression and its mechanism of action to prevent the expression of matrix-metalloproteinases (MMPs) in OA pathogenesis. Interleukin-1 beta (IL-1β), a proinflammatory cytokine as a main causing factor of cartilage destruction, was used to induce OA-like condition of chondrocytes in vitro. Avn-C restrained IL-1β-mediated expression and activity of MMPs, such as MMP-3, -12, and -13 in mouse articular chondrocytes. Moreover, Avn-C alleviated cartilage destruction in experimental OA mouse model induced by destabilization of the medial meniscus (DMM) surgery. However, Avn-C did not affect the expression of inflammatory mediators (Ptgs2 and Nos) or anabolic factors (Col2a1, Aggrecan, and Sox9), although expression levels of these genes were upregulated or downregulated by IL-1β, respectively. The inhibition of MMP expression by Avn-C in articular chondrocytes was mediated by p38 kinase and c-Jun N-terminal kinase (JNK) signaling, but not by ERK or NF-κB. Interestingly, Avn-C added with SB203580 and SP600125 as specific inhibitors of p38 kinase and JNK, respectively, enhanced its inhibitory effect on the expression of MMPs in IL-1β treated chondrocytes. Taken together, these results suggest that Avn-C is an effective candidate to prevent OA progression and a natural health product to relieve OA pathogenesis.

Standardized study of atorvastatin possible osteoarthritis disease-modifying effect in a rat model of osteoarthritis.

We studied the osteoarthritis (OA)-modifying effects of atorvastatin in an experimental OA rat model and possible underlining mechanisms. We used 62 adult male Sprague-Dawley rats (250-300 g): 32 rats were used to assess the effects of atorvastatin on surgically induced OA in the knee, and 30 rats were used to assess the potential inflammatory effects of carrageenan-induced paw edema. In the OA model, joint stiffness was assessed by measuring the knee extension angle, and pathological changes in the OA knee joint were determined by histological examination and the measurement of serum biochemical markers, including interleukin-1β (IL-1β), matrix metalloproteinase-13 (MMP-13), and reduced glutathione (GSH). In the carrageenan-induced paw edema model, both paw thickness and pain threshold were assessed in different groups. Atorvastatin significantly improved joint stiffness, pathological changes, a significant mitigation of the higher MMP-13 and IL-1β, and a significant increase of reduced GSH in OA rats. Additionally, atorvastatin significantly improved both paw thickness and pain threshold in animals. Atorvastatin is a potential OA-modifying drug that warrants further clinical investigation.

Вплив препаратів кріоконсервованої плаценти на перебіг неспецифічного гонартриту в експерименті

Актуальність. Лікування патології суглобів як дегенеративного, так і травматичного генезу — процес тривалий, багатокомпонентний, завжди вимагає спільних зусиль лікаря та пацієнта. Вибір оптимальних засобів терапії складний та неоднозначний. Біологічно активні речовини — одні з потужних засобів боротьби із запальним процесом, що є постійним супутником пошкодження. Завдяки своїм антиоксидантним, імуномодулюючим та регенеративним властивостям фрагменти плаценти визнані перспективним засобом лікування артропатій різної етіології. Мета дослідження — визначення морфологічних характеристик складових структур колінних суглобів щурів у нормі в умовах експериментального артриту та після введення кріоконсервованої плаценти. Матеріали та методи. Експериментальне дослідження проводилось на 115 білих щурах. З інтактною групою (10 тварин) порівнювались 3 контрольні групи по 35 тварин кожна, яким виконувались: 1) моделювання каргінаніндукованого асептичного запалення колінного суглоба; 2) підшкірна імплантація фрагмента плаценти; 3) підшкірна імплантація фрагмента плаценти на фоні асептичного запалення колінного суглоба. Гістологічні препарати готували за загальними методиками із забарвленням гематоксиліном та еозином та за Ван Гізоном. Результати. При створенні запального вогнища зміни в хрящовій тканині визначались із третьої доби у вигляді лакунарності, каріопікнозу як етап некробіозу хондроцитів, що був особливо виражений із 10-ї до 14-ї доби. Морфологічні зміни кісткової тканини щурів, яким вводився ƛ-карагінан, відмічались на 7-му добу дослідження у вигляді резорбції та деструкції кісткових балок. У подальшому (10-та доба) запальний процес призводив до картини фрагментованої архітектоніки кісткової тканини, що спостерігалась до 21-ї доби. Із боку синовіальної оболонки спостерігаються гіперплазія ворсин, лімфоїдна інфільтрація, поява додаткових шарів синовіїцитів як результат проліферативної реакції. Найбільш виражені зміни спостерігались у покривному шарі синовіальної оболонки. При однократному введенні кріоконсервованої плаценти ознаки запалення вірогідно зменшувались: обмежувалась площа деструкції хряща та кістки, у синовіальній оболонці знижувались ознаки мукоїдного набухання. Процеси функціонального кровонаповнення мікроциркуляторного русла переважали над ішемічними. Стимуляція регенеративних процесів забезпечувала структурне відновлення на 21-шу добу спостереження. Висновки. Препарати кріоконсервованої плаценти впливають на перебіг запального процесу в умовах експериментального остеоартриту. Найбільш вірогідний терапевтичний ефект визначається з боку синовіальної оболонки.

Supercritical carbon dioxide decellularized porcine cartilage graft with PRP attenuated OA progression and regenerated articular cartilage in ACLT-induced OA rats.

Knee osteoarthritis (OA) is a common degenerative articular disorder and considered one of the primary causes of pain and functional disability. Knee OA is prevalent in 10% of men and 13% of women aged 60years above. The study aims to use cartilage tissue engineering that combines the triads of decellularized porcine cartilage graft as "scaffold," plasma rich platelet (PRP) as "signal" and chondrocytes from rat as "cell" to attenuate ACLT-induced OA progression and regenerate the knee cartilage in rats. Decellularization of the porcine cartilage was characterized by hematoxylin and eosin, 4,6-Diamidino-2-phenylindole staining, scanning electron microscopy and residual DNA quantification. The protective effect of decellularized porcine cartilage graft (dPCG) was evaluated by intra-articular administration in surgically induced anterior cruciate ligament transection (ACLT) rat osteoarthritis (OA) model. Supercritical carbon dioxide technology completely decellularized the porcine cartilage. Intra-articular administration of dPCG with or without PRP significantly reduced the ACLT-induced OA symptoms and attenuated the OA progression. Pain-relief by dPCG with or without PRP was assessed by capacitance meter and improved articular cartilage damage in the rat knee was characterized by X-ray and micro-CT. Besides, the histological analysis depicted cartilage protection by dPCG with or without PRP. The repairation and attenuation effect by dPCG with or without PRP in the articular knee cartilage damage were also explored by safranin-O, type II collagen, aggrecan and SOX-9 immuno-staining. To conclude, intra-articular administration of dPCG with or without PRP is efficient in repairing the damaged cartilage in the experimental OA model.

Roles and Mechanisms of Irisin in Attenuating Pathological Features of Osteoarthritis.

To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical analyses using (1) murine joint tissues at different developmental stages; (2) human normal and OA pathological tissue samples; (3) experimental OA mouse model; (4) irisin gene knockout (KO) and knock in (KI) mouse lines and their cartilage cells; (5) in vitro mechanistic experiments. We found that Irisin was involved in all stages of cartilage development. Both human and mouse OA tissues showed a decreased expression of irisin. Intra-articular injection of irisin attenuated ACLT-induced OA progression. Irisin knockout mice developed severe OA while irisin overexpression in both irisin KI mice and intraarticular injection of irisin protein attenuated OA progression. Irisin inhibited inflammation and promoted anabolism in chondrogenic ADTC5 cells. Proliferative potential of primary chondrocytes from KI mice was found to be enhanced, while KO mice showed an inhibition under normal or inflammatory conditions. The primary chondrocytes from irisin KI mice showed reduced expression of inflammatory factors and the chondrocytes isolated from KO mice showed an opposite pattern. In conclusion, it is the first time to show that irisin is involved in cartilage development and OA pathogenesis. Irisin has the potential to ameliorate OA progression by decreasing cartilage degradation and inhibiting inflammation, which could lead to the development of a novel therapeutic target for treating bone and cartilage disorders including osteoarthritis.