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ObjectiveTo investigate the intervention effect of Qufeng Gutong Babu ointment （QFGT） on rats with osteoarthritis （OA） with cold-dampness obstruction， and preliminarily clarify its mechanism. MethodSD male rats were divided into 6 groups， namely， the blank group， model group， positive control drug Huoxue Zhitong ointment （HXZTG） group （1.26 cm2·d-1）， and low， medium， and high-dose QFGT group （75， 150， 300 mg·d-1）. OA model was prepared by joint cavity injection of papain and L-cysteine. On the second day of modeling， climate factors were applied to establish an animal model of combination of disease and syndrome of OA rats with cold-dampness obstruction. Standard VonFrey fiber was used to evaluate the threshold of mechanical pain. Weight bearing difference score and joint function score of both hind limbs were recorded. Hematoxylin-eosin （HE） staining and safranine fixation green staining were used to observe the pathological changes and cartilage degeneration of rat knee joint. Immunohistochemistry （IHC） was used to detect the expression of interleukin-1β （IL-1β）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α）， matrix metalloproteinase-9 （MMP-9）， and cathepsin K （CTSK）. Western blot was used to detect the protein expression of kinase B （Akt）， phosphorylated protein kinase B （p-Akt）， phosphatidylinositol 3-kinase （PI3K）， nuclear factor 1 （NFATc1）， MMP-9， and CTSK in T cells. ResultCompared with the normal group， the model group showed significant mechanical pain sensitivity reaction after modeling （P<0.01）， and the weight bearing difference of both hind limbs and joint function score were significantly increased （P<0.05， P<0.01）. Compared with the model group， both the high-dose QFGT group and the HXZTG group significantly reduced the mechanical pain sensitivity， weight difference， and joint function score of rats （P<0.05， P<0.01）， and the medium-dose QFGT group also improved the joint function to a certain extent， and the degeneration of the knee joint cartilage of rats was significantly reduced （P<0.05， P<0.01）. QFGT and HXZTG both inhibited the protein expression of IL-1β， IL-8， TNF-α， MMP-9， CTAK， PI3K， p-Akt， Akt， and other related proteins in articular cartilage of rats with OA to a certain extent （P<0.05， P<0.01）. ConclusionQFGT can inhibit the release of inflammatory factors and matrix metalloproteinases by inhibiting the PI3K/Akt signal pathway in articular articular cartilage of rats with OA with cold-dampness obstruction， thus ultimately weakening local cartilage degeneration and improving joint function.
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Generally, extracellular matrix (ECM) has the characteristics of viscoelasticity. In osteoarthritis (OA), catabolic processes alter the viscoelastic properties of functional pericellular matrix (PCM) of chondrocytes. Chondrocytes sense and respond to their mechanical microenvironment via an array of mechanosensitive receptors and channels that activate a complex network of downstream signaling pathways to regulate several cell processes central to OA pathology. Advances in understanding the specific mechanosignalling mechanisms in articular cartilage will promote the development of cell microenvironment construction in cartilage tissue engineering and the targeted precision therapeutics for OA. In this review, the work on the mechanism of matrix viscoelasticity regulating chondrocytes mechanotransduction by Agarwal et al. was briefly commented, and the recent advances related with their work was also discussed.
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Abnormal mechanical loading is the main risk factor for the development of osteoarthritis (OA), and it can lead to collagen degradation, glycosaminoglycan loss and chondrocyte apoptosis, as well as damage to articular cartilage and subchondral bone. However, due to the lack of understanding in chondrocytes mechanotransduction pathway and invalid method of cartilage repair and regeneration, there is an urgent need for understanding chondrocytes mechanotransduction pathway and mechanism of cartilage damage induced by mechanical loading. In this review, how chondrocytes sense and transmit mechanical signals from cell membrane to cecullar mechanosensors is introduced in detail, and the role of chondrocytes mechanotransduction in OA development is discussed with emphasis.
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Among various types of arthritis Osteoarthritis (OA), Psoriatic arthritis (PA) and Gouty arthritis (GA) are the major ones which have been studied and cause hindrance in movements in many patients. Here we have discussed the treatment modality, a combination of manual therapy and NSAIDs (Ibuprofen) for relieving the symptoms of arthritis. A total of six patients were included consisting of osteoarthritis, psoriatic arthritis and gouty arthritis who presented at the medical office of Dr. Barengolts (MD in USA) and Aybek Izzatov (MD in Uzbekistan) Tyan Anmo Massage School. The study was conducted from October 2019 to March 2020. The treatment consisted of 30 sessions performed for half a year, one week per month (5 days in a month). Significant improvement in symptoms was seen as after 6 months we saw there was reduction in morning stiffness and improved range of motion. The pain score shifted from 5-6 to 2-3 on VAS pain scale. The results signify that the combination therapy wherein manual therapy and NSAIDs worked in an effective way to reduce the level of severity of pain and other associated symptoms.
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Introduction: Rheumatoid arthritis is characterized by local and systemic effects of inflammation while osteoarthritis is aninflammatory degenerative disorder of joints. A wide range of inflammatory markers are implicated in pathogenesis of rheumatoidarthritis and osteoarthritis as a consequence of persistent imbalance between pro- and anti-inflammatory immune mechanisms,leading to chronic inflammation. Hence the present study is an attempt to estimate the levels of serum ceruloplasmin , C-reactiveprotein (CRP) and rheumatoid factor (RF) factor as inflammatory markers in serum of rheumatoid arthritis and osteoarthritispatients and compare them with normal healthy controls. Materials and Methods: Serum ceruloplasmin was estimated byspectrophotometric method while serum C-reactive protein and RA factor were detected using agglutination test in thirty patientsof rheumatoid arthritis ,osteoarthritis and age and sex matched healthy controls each were included in the study. Results:Significant increase in ceruloplasmin was observed (p<0.0001) in rheumatoid arthritis and osteoarthritis as compared to healthycontrols and in that especially ceruloplasmin was more elevated in rheumatoid arthritis than osteoarthritis. C-reactive proteinwas found to be positive in rheumatoid arthritis and osteoarthritis and none of the controls. RF factor was found positive inrheumatoid arthritis and none of the osteoarthritis and controls. Conclusion: There was increased level of serum ceruloplasmin inthe patients with rheumatoid arthritis and osteoarthritis. C-reactive protein and RF factor was found to be positive in rheumatoidarthritis while C-reactive protein was found to be positive in rheumatoid arthritis and osteoarthritis. These findings suggest apossible role of these inflammatory markers in the pathogenesis of rheumatoid arthritis.
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Osteoarthritis (OA) is a chronic degenerative joint disease characterized by joint pain and stiffness, which predisposes to the elderly. The onset of OA is slow, the course of disease is long, and the early clinical manifestations and histological changes are not obvious, which limits the early diagnosis and treatment of the disease. The micro-structure of articular cartilage determines the macro-mechanical properties of cartilage. The micro-structure of articular cartilage changes in a depth-dependent manner, which makes the mechanical properties of cartilage also depth-dependent. From superficial to deep areas of cartilage, the anti-load and anti-deformation ability of cartilage increases gradually. However, with development of the disease, the change of cartilage micro-structure leads to the decrease in load resistance and deformation resistance of OA cartilage. Therefore, the mechanical properties of articular cartilage can be inferred by detecting the micro-structure of articular cartilage. On the other hand, the mechanical properties of articular cartilage can be used to understand the micro-changes of cartilage, which is helpful to understand OA development and facilitate early diagnosis of the disease. This paper reviewed the recent research literatures on mechanical properties of articular cartilage under normal and acute or chronic injuries, and elaborated the relationship between the structure and mechanical properties of articular cartilage, which further provided the theoretical basis for the OA development, early diagnosis and treatment.
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Osteoarthritis (degenerative joint disease) is the most common joint disorder and it mostly affects cartilage. Osteoarthritis (OA) is of two types, primary (idiopathic) and secondary. In idiopathic osteoarthritis, the most common form of the disease, no predisposing factor is apparent. Secondary OA is pathologically indistinguishable from idiopathic OA but is attributable to an underlying cause. The NSAIDs are the main drugs of choice in modern medicine which have lots of side effects and therefore are not safe for long-term therapy. According to Ayurveda OA can be correlated with Sandhivata which is mentioned by Acharya Charak as a sign and symptoms of Sandhigatavata are Shula, Shotha, Stambha, Sparsha-asahyata, Sphutana, Akunchana Prasarana Vedana. The aim of the present study was to see the local effect of Sarsapadi Taila, two times in a day for 30 days. Ingredient of Sarsapadi taila is Sarsap taila, Aadrak and Ajwain. The preparation of Taila was done as mentioned in Sharangdhar Samhita. The ratio of the three components is Kalka (AadraK+ Ajwain) one part, Sneha dravya (Sarsap taila) four parts and Drava (water) should be 16 parts. A pilot study was done in All India institute of Ayurveda hospital. In present study total 25 patients were treated with Sarsapadi Taila which was already taking modern analgesics. After the whole study results were analyzed and tapering the analgesic dose of medicine, there was mild significant changes in the condition of the patients. It is advised to Sarsapadi Taila can be used for the treatment of Sandhivata for a long time.
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Objective To investigate the clinical effect of three capsule combined with Function injection combined with functional exercise in the treatment of knee osteoarthritis.Methods120 patients with knee osteoarthritis were randomly divided into two groups, the study group took orally hydrochloride capsule combined with joints injection combined with functional exercise therapy, and the control group only oral glucose capsules.two groups of patients after a period of treatment.ResultsIn the VAS score, lequesne index and serum inflammatory molecular level of the two groups were significantly better than the control group (P<0.05).ConclusionWhich the clinical study on treating of the knee osteoarthritis by using glucosamine capsule and injecting sodium hyaluronate combined with appropriate functional exercise has a significant effect on knee osteoarthritis, and more favorable in improving the quality of life of patients.
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Objective:To investigate the effects of recombinant human interluekin-1 receptor antogonist (rhIL-1Ra) on the cartilage repair in rat temporomandibular joint(TMJ) with osteoarthritis(OA).Methods:Collagenase-Ⅱ was injected into bilateral TMJs of 24 adult rats for the induction of bilateral TMJOA,1 week after injection,5μg rhIL-1Ra(diluted in 0.05 ml normal saline) was injected into each right TMJ and the left joint received the same amount of normal saline injection as the control.12 animals were sacrificed at 2and 4 weeks after the first injection respectively.HE staining,immunnohistochemical method and RT-PCR examination were conducted.Mankins scere was used to evaluate the TMJOA degree.1 adult SD rat was used as healthy control,and sacrificed at 2 weeks of the experiment.Results:The TMJs of both sides showed typical OA-related cartilage degradation 2 week after IL-1Ra treatment,the Mankin~ score of the IL-1Ra treated and control joints was 1.33±0.52 and 2.00±6.63 (P＞0.05),4 week after treatment that was 3.00± 0.63 and 6.50 ± 0.84 (P＜0.05),respectively.Lower expression of ADAMTS-4 and ADAMTS-5 was observed in the treated joints than in the controls (P＜0.05).Conclusion:Intra-articular injection of IL-1Ra into TMJ can alleviate the cartilage lesion,the mechanism may lie in the inhibition of the expression of ADAMTS-4 and ADAMTS-5.
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Objective:To analysis the correlation of Wnt/β-catenin signaling pathway,OPN and MMP-13 in rabbit model with different degree of osteoarthritis (OA).Methods:Forty New Zealand white rabbits were randomly divided into four groups of 10 each,then we constructed the rabbit model with different degree of osteoarthritis (OA) by different concentrations of papain.The mRNA and protein levels of β-catenin,OPN,MMP-13,type Ⅱ collagen and proteoglycan were detected by Real-Time PCR and ELISA,respectively.Results:We have successfully established OA rabbit model by different concentrations of papain,and these OA rabbits model could be divided into mild,moderate and severe three level by Mankin scoring system,chondrocytes.Compared with the normal control group,the protein levels of β-catenin,OPN,and MMP-13 in the osteoarthritis were significantly increased,while the protein levels of type Ⅱ collagen and proteoglycan were significantly decreased (P＜0.05).With the increasing severity of OA,the results were consistent (P＜0.05).Conclusions:These results indicated that Wnt/β-catenin signaling pathway might regulate the expression of OPN,thereby affecting the expression of MMP-13,and ultimately have an impact on the occurrence ofosteoarthritis.
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Objective To explore the mechanism of reactive oxygen species (ROS) generation on apoptosis of human osteoarthritic chondrocytes induced by cyclic stretch in vitro. Methods The human osteoarthritic chondrocytes were subjected to cyclic stretch at the frequency of 0.5 Hz with 20% elongation. The chondrocytes without cyclic stretch were used as a control. ROS generation in chondrocytes was inhibited by the antioxidant, N-acetyl-L-cysteine (NAC) and potentiated by the glutathione depleter, DL-buthionine-［S,R］-sulfoximine (BSO). Apoptosis was detected by flow cytometry. Intracellular ROS was detected using DCFH-DA and caspase-9 activity was measured using spectrophotometry. Results The cyclic stretch at the frequency of 0.5 Hz with 20% elongation induced ROS generation, and activation of caspase-9 and apoptosis in human osteoarthritic chondrocytes were significantly increased (P<0.05). The inhibition or potentiation of intracellular ROS by NAC or BSO could obviously inhibit or improve caspase-9 activity and apoptosis in chondrocytes under cyclic stretch (P<0.05). Conclusions Cyclic stretch-induced apoptosis in human osteoarthritic chondrocytes is mediated by ROS generation and activation of caspase-9. Suppression of ROS can prevent chondrocytes from apoptosis induced by cyclic stretch.
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Objective To explore the role of mechanical stimulation in synovium under different pathological conditions through studying the effects of cyclic mechanical stretch on the expression of bone morphogenetic protein 2 (BMP-2) in rheumatoid arthritis (RA) and osteoarthritis (OA) fibroblast-like synoviocytes (FLS). Method 6% and 0.5 Hz stretch generated by Flex cell 4000 tension systems was applied on normal, RA and OA FLS of human knee joint source under normal and inflammatory conditions for 2 h or 6 h, respectively. Results Cyclic mechanical stretch of 6%, 0.5 Hz had no significant effects on the expression of BMP-2 in normal, RA and OA FLS at 2 h, while in RA FLS it increased significantly at 6 h. Inflammatory cytokines (IL-1β) didn’t influence normal FLS at 2 h, but made BMP-2 mRNA significantly increased at 6 h. IL-1β increased BMP-2 mRNA of RA FLS significantly both at 2 h and 6 h. IL-1β increased BMP-2 mRNA of OA FLS significantly only at 2 h, but had no significant effect at 6 h. The co-effect of IL-1β and cyclic mechanical stretch induced the ascension of BMP-2 expression significantly in normal and RA FLS at 2 h, and in normal, RA and OA FLS at 6 h. Conclusions Response of BMP-2 mRNA to mechanic stimulation and IL-1β in normal, RA and OA FLS were different. Inflammation may play a more important role than mechanical stimulation in the pathogenesis of RA and OA. Synergetic effect in inflammation and mechanical stimulation were found in OA FLS at 6 h, which reveals that they may co-act in the occurrence and development of OA.
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Objective To investigate the regulation expression of leukemia inhibitory factor(LIF)in hu- man and animal osteoarthritic(OA)tissues and its clinical relevance.Methods 1)Thirty-five Japanese rabbits, aged eight months,were used to make models of experimental osteoarthritis.Operations were performed at the right knee and the sham ones at the left knee in each rabbit.Rabbits were sacrificed on the 3,7,14,28,42,56 and 84 days after operation respectively.Cartilage and synovium of the knee were collected to observe histological changes of osteoarthritis at different times;immunohistochemistry analysis was conducted to observe the LIF expression and distribution in the cartilage and synovium of the animals.2)From April 2003 to October 2003,32 samples of human articular tissues(cartilage,subchondral bone and synovium)were obtained in the operational procedures and a good quantity of RNA was isolated using Magnetic Beads.The patients who underwent articular operations donated the samples.In the reverse transcription-polymerase chain reaction(RT-PCR),the mRNA expression of LIF was mea- sured by semi-quantity analysis and the location of LIF protein was determined by enzyme-linked immunosorbent assay (ELISA).Results A slight expression of LIF was seen in normal cartilage but less in synovium.However,the expression of LIF was remarkable in synovial lining cells,superficial and middle layers of cartilage in animal os- teoarthritis.There was a significant difference in expression between the animal osteoarthritis and the control group (P＜0.05 ).In human tissue study,LIF mRNA was expressed to a very low level in normal articular tissues and there was no significant difference(P＞0.05)between different anatomical locations.In moderate degrading sub- chondral bone,LIF mRNA was expressed to its highest level.LIF was expressed to the highest level in seriously degrading cartilage tissues.The results were similar to ELISA testing results.LIF extents varied in different articular tissue sections.Conclusions LIF is an important mediator that can contribute to tbe pathogenesis of OA.The different temporal and spatial distributions of LIF in normal and OA tissues imply that LIF may play some important roles in pathogenesis of OA.
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A study was undertaken to detennine the point prevalence rates of major rheumatic disorders in Jammu (J&K). WHO-ILAR COPCORD CCQ (World Health Organisation-International League Against Rhewnatism Community Oriented PrograImne for the Control of Rhewnatic Diseases Core Questionnaire) was used followed by clinical examination for the diagnostic purposes. About one-fourth of the population surveyed in this study had rheumatic complaints. LBA was the most frequently encountered rheumatic ailment.