Articular Cavity Research Articles

Changes in rheumatoid arthritis under ultrasound before and after sinomenine injection.

BACKGROUNDRheumatoid arthritis (RA) is a prevalent clinical autoimmune disease that is commonly treated with diclofenac and methotrexate. In recent years, the application of traditional Chinese medicine in RA has received widespread attention; it promotes blood circulation, strengthens the immune system, and eliminates evil. The sinomenine preparation of Zhingqeng Fengtongning is studied as a possible treatment for patients with RA.AIMTo explore the value of sinomenine injection into the articular cavity for the treatment of RA. METHODSA total of 94 patients with RA treated from January 2019 to January 2021 were selected and divided into the study and control groups with 47 patients each using a simple random number table method. Both groups received conventional treatment with diclofenac sodium and methotrexate tablets. The control group received diproxone and lidocaine by intra-articular administration while the study group received an intra-articular administration of the sinomenine preparation of Zhengqing Fengning and lidocaine. χ2 test was used to evaluate the therapeutic effect and synovial thickness, degree of pain through the visual analog scale (VAS), blood flow grade, arthroinflammatory indexes [rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR)] before and after treatment in the two groups. RESULTSThe total effective rate of the study group (93.62%) was higher than that of the control group (78.72%) (P < 0.05). Before treatment, there were no significant differences between the two groups in terms of synovial thickness, VAS score, blood flow grading, levels of RF, and ESR (P > 0.05). After treatment, the synovial thickness and VAS score were significantly lower (P < 0.05) in the study group than in the control group (2.05 ± 0.59 mm vs 2.87 ± 0.64 mm and 2.11 ± 0.62 vs 2.90 ± 0.79 scores, respectively). The rate of blood flow at grade 0 in the study group (76.60%) was higher than that in the control group (57.45%), and the rate of blood flow at grade I (10.64%) was lower than that in the control group (31.91%) (P < 0.05). Furthermore, the levels of RF (55.61 ± 6.13 U/mL), CRP (11.43 ± 3.59 mg/L), and ESR (29.60 ± 5.56 mm/h) in the study group were lower than those in the control group (73.04 ± 9.23 U/mL, 15.07 ± 4.06 mg/L, 36.64 ± 6.10 mm/h, respectively) (P < 0.05).CONCLUSIONSinomenine administration of Zhengqing Fengtongning in the articular cavity with conventional treatment of RA can improve ultrasonographic blood flow and synovial thickness, reduce pain, regulate inflammation, and enhance therapeutic effect.

Injectable “nano-micron” combined gene-hydrogel microspheres for local treatment of osteoarthritis

Sustained and controllable local gene therapy is a potential method for treating osteoarthritis (OA) through the delivery of therapeutic microRNAs (miRNAs) to targeted cells. However, direct injection of crude miRNAs for local gene therapy is limited due to its inadequate transfection efficiency, easy inactivation, and short half-life. Here, a multifunctional gene vector, arginine, histidine, and phenylalanine-modified generation 5 polyamidoamine (named G5-AHP), was employed to form G5-AHP/miR-140 nanoparticles by forming a complex with microRNA-140 (miR-140). Then, the nanoparticles were entrapped in hydrogel microspheres (MSs) to construct a “nano-micron” combined gene hydrogel to alleviate the degradation of articular cartilage. Monodisperse gelatin methacryloyl hydrogel MSs were produced under ultraviolet light using one-step innovative microfluidic technology. Evenly dispersed MSs showed better injectability in sustainable and matrix metalloproteinases (MMPs)-responsive degradation methods for local gene delivery. The G5-AHP/miR-140 nanoparticles released from the MSs exhibited high gene transfection efficacy and long-term bioactivity, facilitated endocytosis, and thus maintained the metabolic balance of cartilage matrix by promoting the expression of type II collagen and inhibiting the expression of a disintegrin and metalloproteinase with thrombospondin motifs-5 and MMP13 in chondrocytes. After injection of the “nano-micron” combined gene hydrogel into the articular cavity of the OA model, the gene hydrogel increased G5-AHP/miR-140 nanoparticle retention, prevented articular cartilage degeneration, and reduced osteophyte formation in a surgically induced mouse model of OA. The present study provides a novel cell-free approach to alleviate the progression of OA that shows potential for locally injected gene delivery systems.

Histological aspects of whole-body vibration in the knee remobilization of Wistar rats

Introduction and aim. The knee is one of the joints where immobilization is most used, however, it can cause morphological changes in the joint tissues and is a challenge to be overcome during rehabilitation. Whole-body vibration (WBV) is capable of generating repetitive oscillatory movements, which cause mechanical stimuli that interfere with tissue plasticity. The aim of this study was to analyze the knee morphology of Wistar rats submitted to remobilization with WBV. Material and methods. 32 male rats were used, divided into four groups (n=8): Control Group (G1), Immobilization Group (G2), Immobilized Group and Free Remobilization (G3), Remobilized Group with WBV (G4). For immobilization, a plastered apparatus was used for 15 days. G3 and G4 carried out free remobilization or with WBV, respectively, for 2 weeks. The knee joints were processed for light microscopy. Results. The WBV led to a reduction in the inflammatory infiltrate in the articular cavity and greater presence of adipocytes in the subintima of the synovial membrane. Conclusion. Remobilization with WBV induced a better tissue response in the synovial membrane when compared to free remobilization.

Study on the Protective Effect and Mechanism of the Rhizoma Drynariae-Epimedium Formula on Osteoarthritis in Rats.

Purpose The aim of the study was to study the protective effect of the Rhizoma Drynariae-Epimedium formula on osteoarthritis in rats and to explore its mechanism. Methods Fifty SD rats were randomly divided into 5 groups, namely, the control group, model group, Rhizoma Drynariae group, Epimedium group, and Rhizoma Drynariae-Epimedium group, with 10 rats in each group. Knee arthritis models were established by injecting papain solution (10% papain + 0.03 mol/L L-cysteine mixture) into the knee joint cavity of SD rats on the 0th, 3rd, and 6th days of the experiment, respectively. The model group, Rhizoma Drynariae group, Epimedium group, and Rhizoma Drynariae-Epimedium group were given modeling treatment, while the control group was not given modeling treatment. The Rhizoma Drynariae group, Epimedium group, and the Rhizoma Drynariae-Epimedium group were, respectively, given corresponding solvent gavage treatment. Both the model group and the control group were given an equal volume of normal saline. Once a day, a total of 4 w were administered. The general conditions of the rats were observed and recorded, and the knee joint width and the knee joint swelling degree of the affected side were measured and compared. HE staining and Safranin O-fast green staining were used to compare the structural changes of cartilage. The concentrations of inflammatory factors IL-1β, IL-6, and TNF-α in the joint cavity lavage fluid were determined by using ELISA. The expression of key proteins of the MAPK signaling pathway (p38, p-p38, ERK, p-ERK, JNK, and p-JNK) in joint synovial tissue was determined by western blotting. Results After modeling, except for the normal activities of the SD rats in the control group, the rest of the groups showed lack of energy and a slight limp in the knee joints. The SD rats in the model group, Rhizoma Drynariae group, Epimedium group, and Rhizoma Drynariae-Epimedium group had local swelling of the knee joint, and the knee joint width was greater than those in the control group (p < 0.05). Compared with the model group, the knee joint swelling of SD rats in the Rhizoma Drynariae group, the Epimedium group, and the Rhizoma Drynariae-Epimedium group was significantly reduced. The knee joint swelling degree of SD rats in the Rhizoma Drynariae-Epimedium group was significantly lower than that in the Rhizoma Drynariae and Epimedium groups. HE staining and Safranin O-fast green staining showed that the cartilage structure of SD rats was severely damaged and eroded, and the subchondral bone mass was reduced. Compared with the model group, the damage of cartilage tissue in the Rhizoma Drynariae group, Epimedium group, and Rhizoma Drynariae-Epimedium group was less severe. In the Rhizoma Drynariae-Epimedium group, cartilage tissue structure damage and erosion were lighter than those of the Rhizoma Drynariae group and the Epimedium group. The concentrations of inflammatory factors IL-1β, IL-6, and TNF-α in the articular cavity lavage fluid of SD rats in the model group, Rhizoma Drynariae group, Epimedium group, and Rhizoma Drynariae-Epimedium group were higher than those in the control group. Compared with the model group, the concentrations of IL-1β, IL-6, and TNF-α in the joint cavity lavage fluid of the Rhizoma Drynariae group, Epimedium group, and Rhizoma Drynariae-Epimedium group were significantly decreased. In the Rhizoma Drynariae-Epimedium group, IL-1β, IL-6, and TNF-α concentrations were lower than those of the Rhizoma Drynariae and Epimedium groups. Compared with the control group, the expression levels of p-p38, p-ERK, and p-JNK proteins in the model group, Rhizoma Drynariae group, Epimedium group, and Rhizoma Drynariae-Epimedium group were significantly increased. The expression levels of p-ERK, p-p38 and p-JNK in the Drynariae group, Epimedium group, and Drynariae-Epimedium group were significantly lower than those in the model group. The expression levels of p-ERK, p-p38, and p-JNK in the Rhizoma Drynariae-Epimedium group were significantly lower than those in the Rhizoma Drynariae and Epimedium groups. Conclusion The Rhizoma Drynariae-Epimedium formula can play a protective role in the process of osteoarthritis by inhibiting the phosphorylation levels of p38, ERK, and JNK-related proteins in the cartilage tissue MAPK signaling pathway, reducing the inflammatory response.

Effect of Sodium Hyaluronate and Betamethasone Injection in Knuckle Articular Cavity on Serum Inflammatory Factors and Metalloproteinase of Knee Osteoarthritis Patients

Effect of Sodium Hyaluronate and Betamethasone Injection in Knuckle Articular Cavity on Serum Inflammatory Factors and Metalloproteinase of Knee Osteoarthritis Patients

Development of the temporomandibular joint in miniature pig embryos.

The temporomandibular joint (TMJ) is a synovial joint involved in sliding and hinge movements of lower jaw in mammals. Studies on TMJ development in embryos have been mainly performed using rodents. However, the TMJ structure in rodents differs in several aspects from that in humans. There are few studies on the embryonic development of TMJ in large mammals. In the present study, we investigated the embryonic developmental characteristics of the TMJ in pigs histologically. Embryonic day 35 (E35), E45, E55, E75, E90, and postnatal day 1(P1) embryos/fetuses from the pigs were used for the study. The results showed condensation of mesenchymal cells on E35. The inferior articular cavity was formed on E45, together with a narrow crack in the superior articular cavity region. The superior and inferior articular cavities and articular disc of the TMJ were completely formed on E55. On E75, the condyle showed an obvious conical shape and the superior and inferior joint cavities were enlarged. Furthermore, the mandibular ramus and mandibular body under the neck of the condyle were ossified from E75 to P1 day. The chondrocyte layer of the condyle was significantly thinner from E75 to P1. It is speculated that the spatiotemporal development of the TMJ in miniature pig embryos is similar to that in humans. Embryonic development of the pig TMJ is an important bridge for translating the results of rodent research to medical applications.

Мануальна терапія у хворих на дисфункцію крижово-клубового суглоба

Актуальність. Низка авторів вважають, що дисфункція крижово-клубового суглоба (ККС) супроводжується появою його асиметричної рухливості. Тому логічно припустити, що технології, спрямовані на відновлення рухливості цього суглоба, сприятимуть відновленню опороздатності ККС і будуть давати добрий клінічний ефект. Мета: дослідження ефективності мануальної терапії у пацієнтів з дисфункцією ККС залежно від асиметрії ширини суглобових щілин у фронтальній площині. Матеріали та методи. Нами обстежена група з 56 пацієнтів зі скаргами на тривалі попереково-тазові болі. Вік пацієнтів був від 18 до 71 року. Середній вік становив 38,7 року. Хворі обстежені клінічно та рентгенологічно. На попередніх етапах дослідження пацієнти з дисфункцією ККС були розподілені на чотири рентгенометричні групи. Всім пацієнтам виконувалася мануальна терапія ККС 1 раз на тиждень. До і після сеансу мануальної терапії у пацієнтів визначали інтенсивність болю за візуальною аналоговою шкалою (ВАШ) і проводилися такі провокативні тести: Stork-тест і ASLR-тест. ASLR-тест вимірювався від 1 до 5 балів. Якщо після мануальної терапії пацієнт відчував полегшення, сеанс повторювали через тиждень. Проводили не більше 2 сеансів мануальної терапії для кожного хворого. Якщо пацієнт відзначав загострення болю або відсутність полегшення, то мануальну терапію більше не повторювали. Отримані дані були оброблені статистично. Результати. Проведений статистичний аналіз даних Stork-тесту показав, що до лікування у всіх хворих тест був позитивним, після лікування у 5 хворих І групи (62,5 %) тест став негативним, але у 3 (37,5 %) залишався позитивним, що і зумовило незначущий результат лікування хворих в цій групі. У ІІ групі хворих після лікування Stork-тест став негативним у 18 хворих (78,3 %), а позитивний результат показали 5 (21,7 %) хворих. Результат лікування був значущим. У ІІІ групі після лікування тільки у 3 (18,8 %) хворих тест став негативним, у 13 (81,2 %) залишився позитивним, стан хворих цієї групи залишився на колишньому рівні. У хворих IV групи результати Stork-тесту залишилися без зміни. Аналіз результатів ASLR-тесту показав, що у хворих І та ІІ групи спостерігалося значне поліпшення стану. У хворих ІІІ групи спостерігалися видимі, але незначущі поліпшення. У хворих IV групи результати погіршилися, тобто якщо до лікування значення тесту у хворих було практично однаковим, то після лікування спостерігалося значне його збільшення. Після лікування статистично було показано, що у хворих І та ІІ групи настало значне зменшення вираженості больового синдрому в середньому на 26 ÷ 27 балів. У хворих ІІІ групи поліпшення хоча і було значущим, проте середнє зменшення больового синдрому становило всього 6,3 ± 4,8 бала. У хворих IV групи наступило значне збільшення ступеня больового синдрому з 55,8 ± 3,8 до 74,3 ± 6,2 бала — в середньому на 18,6 ± 5,3 бала. При цьому до і після лікування інтенсивність больового синдрому в групах була статистично різною, але якщо до лікування показник за ВАШ в III і IV групах був близьким, то після лікування показник за ВАШ IV групи вже статистично був гірше від всіх інших груп. Висновки. Мануальна терапія є ефективною технологією лікування пацієнтів з дисфункцією ККС з великою асиметрією ширини суглобових щілин в вентральному і медіальному відділах ККС і невеликою асиметрією ширини суглобових щілин у всіх відділах ККС. Мануальна терапія протипоказана пацієнтам з дисфункцією ККС з великою асиметрією ширини суглобових щілин в дорсальних відділах суглобових щілин ККС.

Chitosan hydrogel/3D-printed poly(ε‐caprolactone) hybrid scaffold containing synovial mesenchymal stem cells for cartilage regeneration based on tetrahedral framework nucleic acid recruitment

Articular cartilage (AC) injury repair has always been a difficult problem for clinicians and researchers. Recently, a promising therapy based on mesenchymal stem cells (MSCs) has been developed for the regeneration of cartilage defects. As endogenous articular stem cells, synovial MSCs (SMSCs) possess strong chondrogenic differentiation ability and articular specificity. In this study, a cartilage regenerative system was developed based on a chitosan (CS) hydrogel/3D-printed poly(ε‐caprolactone) (PCL) hybrid containing SMSCs and recruiting tetrahedral framework nucleic acid (TFNA) injected into the articular cavity. TFNA, which is a promising DNA nanomaterial for improving the regenerative microenvironment, could be taken up into SMSCs and promoted the proliferation and chondrogenic differentiation of SMSCs. CS, as a cationic polysaccharide, can bind to DNA through electrostatic action and recruit free TFNA after articular cavity injection in vivo. The 3D-printed PCL scaffold provided basic mechanical support, and TFNA provided a good microenvironment for the proliferation and chondrogenic differentiation of the delivered SMSCs and promoted cartilage regeneration, thus greatly improving the repair of cartilage defects. In conclusion, this study confirmed that a CS hydrogel/3D-printed PCL hybrid scaffold containing SMSCs could be a promising strategy for cartilage regeneration based on chitosan-directed TFNA recruitment and TFNA-enhanced cell proliferation and chondrogenesis.

Dynamic changes of the joint capsule in relation to the zona orbicularis: An anatomical study with possible implications for hip stability mechanism.

The zona orbicularis, which comprises the inner circular fibers of the joint capsule, is vital for hip stability in distraction. Despite the proximity of the whole joint capsule to the zona orbicularis, their anatomical relationship remains unclear. The aim of this study is to investigate the characteristics of the inner side of the joint capsule comprehensively. Twelve hips from nine bodies donated to science were examined. Six and three of the donated bodies, respectively, were embalmed using 8% formalin and Thiel's method. The joint capsules in three formalin‐embalmed bodies were sturied by micro‐computed tomography. During formalin fixation of six hips from these three bodies, one side was maintained at hip extension and the other at flexion. The remaining three formalin‐embalmed bodies were examined histologically. Micro‐computed tomography images revealed that the inward protrusion of the joint capsule narrowed the articular cavity, and the ratio of its narrowest area to that of the femoral neck was less at hip extension than at hip flexion. The Thiel's method specimens showed that the inner surface of the joint capsule protruded inward toward the femoral neck during hip extension. This inward protrusion was not histologically independent of the joint capsule. The zona orbicularis was interpreted as the inward protrusion caused by dynamic change of the joint capsule, rather than the local collar. In other words, the joint capsule could change its morphology dynamically depending on the hip position.

Intra-Articular Injection of a Nanosuspension of Tetramethylpyrazine Dihydroxynaphthalenate for Stronger and Longer-Lasting Effects Against Osteoarthritis.

Tetramethylpyrazine (TMP), isolated from the rhizome of the traditional Chinese medicinal plant Chuanxiong (Ligusticum wallichii Franchat) shows therapeutic efficacy against osteoarthritis. After intra-articular injection, the retention time of TMP in the joint cavity is short, which limits its treatment effect. To avoid this problem, the present study explored the preparation of a TMP nanosuspension (TMP-NS) based on hydrophobic ion pairing. TMP-NS showed a particle size of approximately 588 nm and, after intra-articular injection in rats, it had longer retention in the articular cavity, higher TMP concentrations in joints, and greater anti-osteoarthritic efficacy than TMP solution. TMP-NS didn't cause significant inflammation at the joint. These results suggest that TMP-NS may strengthen and prolong the therapeutic efficacy of TMP against osteoarthritis without systemic toxicity.

The microarchitecture of the tissues of the shoulder joint in dogs

Up to the present time practically not studied the peculiarities of formation of cartilage in the various compartments of the shoulder joint in dogs, as well as zones of least resistance joints in General. Available studies mainly use visual diagnostic methods, without applying morphological and morphometric. There is no information about age-related cytomorphological transformations occurring in the joint in normal and pathological conditions. In this regard, the aim of our study was to determine the zone of risk of damage to the shoulder joint in dogs. Studies were conducted on dogs and cadaver material, selected from giant, large and mediumsized breeds. Arthroscopic studies of dogs were performed, as well as light microscopy of histological sections of freshly treated samples of joint tissues. As a result of trauma to the joint is transformed physiological synovial folds in sklerozirovanie a pathological form that occurs in German shepherd dogs over 5 years of age in 60% of cases. The process of mineralization of the matrix and the appearance of multiple foci of ossification occurs asynchronously in the cartilage of the head of the humerus and the articular cavity of the scapula. Osteoplastic processes in the area of articulation occur unevenly. Cartilage coating of the articular surface of the shoulder blade is characterized by a more uniform distribution than the articular rotation of the humerus head. The zones of risk of damage to the structures of the shoulder joint in dogs were determined. These include: cranial and medial compartments of the joint, the caudal area of the cartilaginous coating of the humerus, the caudal area of the articular surface of the scapula cavity. The data obtained make up for the information about the diagnosis and risk factors in the development of shoulder joint pathologies in dogs of large and giant breeds. They should be used in clinical diagnosis and surgery of the musculoskeletal system in animals.

Pharmacokinetics, distribution and efficacy of triptolide PLGA microspheres after intra-articular injection in a rat rheumatoid arthritis model

The UPLC-MS/MS method was established with good precision, accuracy and stability to determine the concentrations of TPL in biological samples, such as heart, liver, spleen, lung, kidney, plasma and joint. After being made into microspheres, TPL can stay in the joint tissue for a long time, further reducing the number of times joint cavity administration, and its sustained release effect was significantly improved compared with the solution dosage form. The pharmacokinetic parameters, such as AUC(0–t), AUC(0–∞), T 1/2, T max, MTR(0–t), and MTR(0–∞) of the TPL-PLGA-MS group were significantly increased compared with those of the solution group. The microsphere preparation could significantly slow the release rate of the drug from the joint cavity. TPL-PLGA-MS can significantly reduce the expression of inflammatory factors such as IL-1, IL-6, TNF-α and hs-CRP. TPL-PLGA-MS for articular cavity injection has potential as a new preparation for the treatment of RA.

Pravastatin ameliorated osteoarthritis susceptibility in male offspring rats induced by prenatal ethanol exposure.

Osteoarthritis (OA) is a disease associated with a disorder of cholesterol metabolism. Our previous studies showed that prenatal ethanol exposure (PEE) caused cholesterol accumulation in articular cartilage and increased the susceptibility to OA in offspring. However, we did not determine whether pravastatin, a cholesterol-lowering agent, could rescue PEE-induced susceptibility to OA. Here, fetal rats were divided into a PEE group and a control group during pregnancy. At postnatal week (PW) 8, sixteen male offspring rats from both groups were injected papain through the articular cavity. Eight of them from each group were treated with pravastatin (20mg/kg·d) by gavage for four weeks simultaneously. We found that pravastatin ameliorated papain-induced high expression of inflammatory factors [interleukin (IL)-1, IL-6], matrix degradation enzymes [matrix metalloproteinase (MMP)-3, MMP-13], and apoptosis factors (caspase-3 and caspase-8) in the cartilage of the PEE group. Also, pravastatin significantly reduced the content of TCH in the blood and cartilage of the PEE offspring and improved cholesterol efflux pathway. Our in vitro findings further confirmed that pravastatin partially reversed cholesterol-induced inflammation and apoptosis of chondrocytes. In conclusion, pravastatin effectively reduced inflammation and matrix degradation, and thus ameliorate OA susceptibility in articular cartilage by relieving cholesterol accumulation in chondrocyte.

Clinical analysis of arthroscopy used in the diagnosis and treatment of synovial chondromatosis of the temporomandibular joint

To evaluate the value of arthroscopy in the diagnosis and treatment of synovial chondromatosis of the temporomandibular joint (TMJSC). The cases of 16 patients preliminarily diagnosed with TMJSC by magnetic resonance imaging (MRI) from July 2011 to December 2018 were analyzed retrospectively. If the diagnosis was confirmed by arthroscopy, the opening operation was performed. The preoperative MRI, arthroscopy and opening operation, postoperative pathology and postoperative MRI of confirmed cases were analyzed, and clinical follow-up was performed to evaluate the curative effect of open surgery. The degree of mouth opening and visual analogue scale (VAS) scores for pain pre-operation and during follow-up of the confirmed cases were analyzed by t-test. Fourteen cases of TMJSC were diagnosed by arthroscopy, consistent with the postoperative pathological diagnosis. Postoperative MRI examination showed that articular cavity lesions basically disappeared. Ten patients with synovial chondromatosis were followed-up (follow-up rate, 71.4%) from 6 months to 7 years and 8 months (average follow-up time, 17.6 months); no recurrence was found, and clinical symptoms improved by varying degrees. Before operation and at follow-up, t-test results of opening degree difference were t=7.757, P<0.05; t-test results of VAS were t=-3.274, P<0.05. Arthroscopy is essential in the diagnosis and treatment of TMJ synovial chondromatosis.

Effect of Hedyotis diffusa Willd extract on gouty arthritis in rats

Purpose: To investigate the effect of Hedyotis diffusa Willd extract (HDWE) on gouty arthritis in rats.Method: Monosodium urate (MSU) crystal was injected into the ankle joint of rats to establish a rat model of gouty arthritis. HDWE (4.8, 9.6 and 19.2 g/kg) was administered to the rats treated with MSU crystals. The walking behavior of the rats was observed daily, and the gait score was calculated to evaluate the Oswestry disability index of rats. Levels of IL-1β and TNF-α in lavage fluid of articularcavities were measured using enzyme linked immunosorbent assay (ELISA) kits. The synovial tissues of joint of control, model and 19.2 g/kg HDWE group rats were obtained and NLRP3 inflammasome was analysed by Western blot.Results: The results showed that HDWE ameliorated the symptoms of gouty arthritis and gait score in rats significantly (p &lt; 0.05). Further pharmacological experiments showed that all doses of HDWE decreased the levels of inflammatory cytokines IL-1β and TNF-α (p &lt; 0.05), and inhibited NLRP3, caspase-1, ASC, IL-1β and IL-18 protein expressions of the lavage fluid of articular cavities in MSU crystal-treated rats (p &lt; 0.01).Conclusion: The results indicate that HDWE exhibits a significant effect in ameliorating gouty arthritis via inhibition NLRP3 inflammasome, and thus is a potential new drug choice for the treatment of gouty arthritis.&#x0D; Keywords: Hedyotis diffusa, Caspase, Gouty arthritis, Inflammatory cytokines, NLRP3 inflammasom

Acidosis induces synovial fibroblasts to release vascular endothelial growth factor via acid-sensitive ion channel 1a

AbstractAcid-sensitive ion channel 1a (ASIC1a) is a member of the extracellular H+ activated cation channel family. Studies have shown that tissue acidification contributes to the formation of microvessels in rheumatoid arthritis (RA) synovial tissue, but its underlying mechanisms remain unclear. The purpose of this study was to investigate the role of tissue acidification in microvascular formation of arthritic synovial tissue and the effect of ASIC1a on vascular endothelial growth factor (VEGF) release from arthritic synovial tissue. Our results indicate that ASIC1a expression, VEGF expression, and microvessel density (MVD) are elevated in RA synovial tissue and adjuvant arthritis (AA) rat synovial tissue. When AA rats were treated with ASIC1a-specific blocker psalmotoxin-1 (PcTx-1), the expression of ASIC1a, VEGF expression, and MVD were all reduced. Acidification of RA synovial fibroblasts (RASF) can promote the release of VEGF. PcTx-1 and ASIC1a-short hairpin RNA can inhibit acid-induced release of VEGF. In addition, the ASIC1a overexpression vector can promote acid-induced VEGF release. This indicates that extracellular acidification induces the release of VEGF by RASF via ASIC1a. These findings suggest that blocking ASIC1a mediates the release of VEGF from synoviocytes may provide a potential therapeutic strategy for RA therapy.Both ASIC1a and VEGF are highly expressed in rheumatoid arthritis synovial tissue and are associated with vascular disease. Interfering with ASIC1a in vitro using silencing, blocking, and overexpression interferes with the release of VEGF under acid stimulation. Blocking ASIC1a in the articular cavity of rats with adjuvant arthritis not only reduces the expression of VEGF in the synovium, but also reduces the proliferation and lesions of blood vessels and interferes with the development of the disease.

Enhancement of acellular cartilage matrix scaffold by Wharton's jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration

Articular cartilage defect repair is a problem that has long plagued clinicians. Although mesenchymal stem cells (MSCs) have the potential to regenerate articular cartilage, they also have many limitations. Recent studies have found that MSC-derived exosomes (MSC-Exos) play an important role in tissue regeneration. The purpose of this study was to verify whether MSC-Exos can enhance the reparative effect of the acellular cartilage extracellular matrix (ACECM) scaffold and to explore the underlying mechanism. The results of in vitro experiments show that human umbilical cord Wharton's jelly MSC-Exos (hWJMSC-Exos) can promote the migration and proliferation of bone marrow-derived MSCs (BMSCs) and the proliferation of chondrocytes. We also found that hWJMSC-Exos can promote the polarization of macrophages toward the M2 phenotype. The results of a rabbit knee osteochondral defect repair model confirmed that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration. We demonstrated that hWJMSC-Exos can regulate the microenvironment of the articular cavity using a rat knee joint osteochondral defect model. This effect was mainly manifested in promoting the polarization of macrophages toward the M2 phenotype and inhibiting the inflammatory response, which may be a promoting factor for osteochondral regeneration. In addition, microRNA (miRNA) sequencing confirmed that hWJMSC-Exos contain many miRNAs that can promote the regeneration of hyaline cartilage. We further clarified the role of hWJMSC-Exos in osteochondral regeneration through target gene prediction and pathway enrichment analysis. In summary, this study confirms that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration.

Study on the ability of type I collagen bioactive nanomaterial scaffold to repair spontaneous cartilage injury

Objective: Natural bone tissue can be considered as a complex composed of type I collagen and light-based apatite with low crystallinity. Choosing type I collagen and light-based apatite as bone repair materials can realise the biomimetic of natural bone. Chitosan is easy to mix with collagen, and the interaction of the two at the molecular level can make the complex of the two more stable than any single component. However, due to the poor mechanical properties of collagen and chitosan, the high swelling degree of collagen, the greater brittleness of light-based apatite, and the incompatibility with organics, the high swelling degree and the rapid degradation of this material limit the use of similar materials in bone tissue engineering. In this paper, the ultrastructure of type I collagen scaffolds is analysed; goat knee cartilage defect models are established using green goats as experimental animals. Fifteen 12-month-old goats are randomly divided into three groups, each with 10 knees, and group A is blank, the control group, group B is a simple collagen I collagen double-layer scaffold group, and group C is a type I collagen double-layer scaffold combined with MSCs transplantation group, which is treated according to the experimental group; materials are taken at 6 weeks and 24 weeks after the operation gross observation and histological scores were used to evaluate the repair effect of each group. Successfully established goat knee cartilage defect model and type I double-layer collagen scaffold composite autologous bone marrow mesenchymal stem cells (BMSCs) implantation technology. At 24 weeks postoperative MRI, there was no effusion in the articular cavity and no synovial hyperplasia. The repair tissue in the experimental group had no difference in signal from normal cartilage; the repair tissue was observed to be flat with normal cartilage and similar in colour to normal cartilage. Histology confirmed the repaired tissue as hyaline cartilage. The Waitangi score in the experimental group was 2.65 ± 1.36, which was significantly better than that in the stent group alone (7.04 ± 2.14) and the blank control group (10.87 ± 3.51). The blank control group and the stent group had poor repair effect.

Сравнительная оценка поведения гелей на основе поливинилпирролидона в условиях in vitro и in vivo

A series of experiments aimed at studying antimicrobial properties of gel experimental samples has been carried out, and their prolonged action in vivo and in vitro has been compared. The gel under study is a processed composition based on polyvinylpyrrolidone (PVP) and antimicrobial drugs; it is intended for the prevention and treatment of implant-associated infection in traumatology and orthopedics. Two methods were used to process the composition: ionizing radiation and heating. PVP treated in this way is a matrix for drug delivery to the structures of the articular cavity, which allows using antimicrobial medicines, in particular gentamicin and fosfomycin, for targeted influence on infectious agents. All gel samples, regardless of the method for their preparation, exhibited antimicrobial activity against Staphylococcus aureus, the main causative agent of postoperative infectious processes. The antimicrobial properties of the gel were long-lasting; they were observed for 14 days. No pathological changes were found in the tissues adjacent to the gel. Key words: implant-associated infection, surgery, traumatology, biofilm, polymer hydrogel, gentamicin, fosfomycin

Self-assembled lyotropic liquid crystal gel for osteoarthritis treatment via anti-inflammation and cartilage protection.

Osteoarthritis (OA) is a chronic joint disease with occurrence of articular inflammation and cartilage degeneration. An ideal drug delivery system for effective treatment of OA should integrate inflammation alleviation with cartilage protection. Herein, a lyotropic liquid crystal (LLC) precursor co-loading hyaluronic acid (HA) and celecoxib, formulated as the HLC precursor, was developed for the combined therapeutic efficacy. The in situ gelling property of the HLC precursor effectively prolongs drug retention in the articular cavity to achieve a long-term anti-inflammation effect. Based on the rheological tests, HLC gel with a cubic lattice structure endows it with a spring-like effect to buffer joint shock and shows great potential in providing cartilage protection by resisting mechanical destruction, lubricating joint, and decomposing intensive stress (about 50%). Meanwhile, the pharmacodynamics study on the OA-induced SD rats demonstrated that HLC gel was the most effective to reduce inflammation levels and to protect the cartilage against abrasion and degeneration. Furthermore, the in vivo degradation behavior and the intra-articular irritation results of LLC/HLC gel demonstrated that it was biodegradable and biocompatible. These results collectively demonstrated that HLC gel with anti-inflammation and cartilage protection performance provides a useful approach to treat OA.