scholarly journals Sodium Monoiodoacetate Dose-Dependent Changes in Matrix Metalloproteinases and Inflammatory Components as Prognostic Factors for the Progression of Osteoarthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Marta Bryk ◽  
Jakub Chwastek ◽  
Jakub Mlost ◽  
Magdalena Kostrzewa ◽  
Katarzyna Starowicz

Osteoarthritis (OA) is a degenerative joint disease that primarily affects people over 65 years old. During OA progression irreversible cartilage, synovial membrane and subchondral bone degradation is observed, which results in the development of difficult-to-treat chronic pain. One of the most important factors in OA progression is joint inflammation. Both proinflammatory and anti-inflammatory factors, as well as extracellular matrix degradation enzymes (matrix metalloproteinases (MMPs), play an important role in disease development. One of the most widely used animal OA models involves an intra-articular injection of sodium monoiodoacetate (MIA) directly into the joint capsule, which results in glycolysis inhibition in chondrocytes and cartilage degeneration. This model mimics the degenerative changes observed in OA patients. However, the dose of MIA varies in the literature, ranging from 0.5 to 4.8 mg. The aim of our study was to characterize grading changes after injection of 1, 2 or 3 mg of MIA at the behavioral and molecular levels over a 28-day period. In the behavioral studies, MIA injection at all doses resulted in a gradual increase in tactile allodynia and resulted in abnormal weight bearing during free walking sequences. At several days post-OA induction, cartilage, synovial membrane and synovial fluid samples were collected, and qPCR and Western blot analyses were performed. We observed significant dose- and time-dependent changes in both gene expression and protein secretion levels. Inflammatory factors (CCL2, CXCL1, IL-1β, COMP) increased at the beginning of the experiment, indicating a transient inflammatory state connected to the MIA injection and, in more severe OA, also in the advanced stages of the disease. Overall, the results in the 1 mg MIA group were not consistently clear, indicating that the lowest tested dose may not be sufficient to induce long-lasting OA-like changes at the molecular level. In the 2 mg MIA group, significant alterations in the measured factors were observed. In the 3 mg MIA group, MMP-2, MMP-3, MMP-9, and MMP-13 levels showed very strong upregulation, which may cause overly strong reactions in animals. Therefore, a dose of 2 mg appears optimal, as it induces significant but not excessive OA-like changes in a rat model.

2020 ◽  
Vol 82 (6) ◽  
pp. 64-73
Author(s):  
O.H. Korotkyi ◽  
◽  
T.V. Luhovska ◽  
T.M. Serhiychuk ◽  
K.O. Dvorshchenko ◽  
...  

Osteoarthritis is a most widespread chronic degenerative joint disease that causes pain, cartilage deformation, and joint inflammation. Adverse alterations of intestinal microbiota like dysbiosis may lead to metabolic syndrome and inflammation, two important components of osteoarthritis progression. Aim. In this study we investigated the effect of chondroitin sulfate and probiotics on the gut microbiome in monoiodoacetate-induced osteoarthritis model in rats. Methods. The species and quantitative composition of feces were determined using diagnostic media with selective properties. Further identification of isolated microorganisms was carried out according to morphological, tinctorial, physiological and metabolic parameters. The results are presented in the form of lg CFU/g. Results. Induction of osteoarthritis caused significant increasing the number of opportunistic enterobacteria and lactose-negative Escherichia coli against the decreasing of lacto- and bifidobacteria that may indicate a dysbiotic condition. Coadministration of chondroitin sulfate and probiotic bacteria has led to improvement the quantitative composition of the gut microbiota in experimental animals, the numerous of Bifidobacterium, Lactobacillus were increasing against decreasing the quantitative composition of opportunistic microorganisms. Conclusions. Monoiodoacetate-induced osteoarthritis caused dysbiosis of gut in rat. We observed beneficial effect of combined administration of chondroitin sulfate and probiotics on gut microbiota composition in rats with experimental osteoarthritis. Thus, adding of supplements like probiotics to standard treatment of osteoarthritis may have potentials to prevent and treat this disease.


2021 ◽  
Author(s):  
Ding-Chao Zhu ◽  
Yi-Han Wang ◽  
Jia-Hao Lin ◽  
Zhi-Min Miao ◽  
Jia-Jing Xu ◽  
...  

Osteoarthritis (OA) is a common degenerative joint disease characterized by articular cartilage degeneration and inflammation. Currently, there is hardly any effective treatment for OA due to its complicated pathology and...


Processes ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 873
Author(s):  
Donghun Lee ◽  
Chae Yun Baek ◽  
Ji Hong Hwang ◽  
Mi-Yeon Kim

Osteoarthritis (OA), being the most prominent degenerative joint disease is affecting millions of elderly people worldwide. Although Andrographis paniculata is an ethnic medicine with a long history of being used as analgesic agent, no study using a monosodium iodoacetate (MIA) model has investigated its potential activities against OA. In this study, experimental OA was induced in rats with a knee injection of MIA, which represents the pathological characteristics of OA in humans. A. paniculata extract (APE) substantially reversed the loss of hind limb weight-bearing and the cartilage damage resulted from the OA induction in rats. Additionally, the levels of serum pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α as well as the concentration of matrix metalloproteinases, including MMP-1, MMP-3, MMP-8, and MMP-13 were decreased by APE administration. Acetic acid-induced writhing responses in mice which quantitatively measure pain were significantly reduced by APE. In vitro, APE inhibited the generation of NO and downregulated the expression of IL-1β, IL-6, COX-2, and iNOS in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The above results suggest the potential use APE as a therapeutic agent against OA.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Guiqiang Miao ◽  
Xuehui Zang ◽  
Huige Hou ◽  
Hui Sun ◽  
Lihui Wang ◽  
...  

Osteoarthritis (OA) is a chronic degenerative joint disease, where chondrocyte apoptosis is responsible for cartilage degeneration. Bax is a well-known proapoptotic protein of the Bcl-2 family, involved in a large number of physiological and pathological processes. However, the regulation mechanisms of Bax underlying chondrocyte apoptosis in OA remain unknown. In the present study, we determined the role of Bax in human OA and chondrocyte apoptosis. The results showed that Bax was upregulated in chondrocytes from the articular cartilage of OA patients and in cultured chondrocyte-like ATDC5 cells treated by IL-1β. Bax was identified to be the direct target of miR-29a by luciferase reporter assay and by western blotting. Inhibition of miR-29a by the mimics protested and overexpression by miR-29a inhibitors aggravated ATDC5 apoptosis induced by IL-1β. These data reveal that miR-29a/Bax axis plays an important role in regulating chondrocyte apoptosis and suggest that targeting the proapoptotic protein Bax and increasing expression levels of miR-29a emerge as potential approach for protection against the development of OA.


Author(s):  
T. Vaughan-Scott ◽  
J.H. Taylor

Osteoarthritis or degenerative joint disease is a condition characterised by degeneration of articular cartilage often associated with the formation of new bone at joint surfaces or margins. Commonly encountered in dogs, osteoarthritis may have a gradual onset, but may also occur acutely. Osteoarthritis can be a primary disease of joint cartilage, but is more often secondary to abnormal stresses on joints. This article describes the pathogenesis and progression of cartilage degeneration as well as the dietary, lifestyle and pharmacological management of osteoarthritis. Recent pharmacological developments allow the clinician not only to control clinical signs of the disease, but also to slow the progression of cartilage degeneration.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jun Yamada ◽  
Kunikazu Tsuji ◽  
Kazumasa Miyatake ◽  
Yu Matsukura ◽  
Kahaer Abula ◽  
...  

Activins are proinflammatory cytokines which belong to the TGFβsuperfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration.


2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Safwat Adel Abdo Moqbel ◽  
Yuzhe He ◽  
Langhai Xu ◽  
Chiyuan Ma ◽  
Jisheng Ran ◽  
...  

As a joint disease, osteoarthritis (OA) is caused by the breakdown of subchondral bone and cartilage damage. Inflammatory factors, such as interleukin- (IL-) 1β, mediate the progression of OA. Madecassoside (MA), a triterpenoid component derived from the gotu kola herb (Centella asiatica), exhibits various pharmacological effects, including antioxidative and anti-inflammatory properties. In the present study, the protective effects and possible mechanism of MA on the treatment of OA were investigated. MA was demonstrated to significantly suppress the IL-1β-induced overexpression of matrix metalloproteinase- (MMP-) 3, MMP-13, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) and to decrease the IL-1β-induced degradation of type II collagen and sox9. Additionally, MA was able to reduce the IL-1β-induced phosphorylation of p65 in osteoarthritic chondrocytes. Furthermore, in a rat OA model, MA prevented cartilage degeneration and reduced the OARSI score in the MA-treated group compared with the OA group. The present study showed that MA suppresses the nuclear factor-κB signaling pathway, reducing IL-1β-induced chondrocyte inflammation, which indicates the therapeutic potential of MA in patients with OA.


2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0025
Author(s):  
Christopher Hyer ◽  
Nisha Shah ◽  
Marcus Richardson

Category: Midfoot/Forefoot Introduction/Purpose: The first metatarsophalangeal joint (MTPJ) is an integral part of the foot during the gait cycle. Arthrodesis of this joint is gold standard, especially in patients with rheumatoid arthritis. The development of IPJ arthritis after an arthrodesis of the MTPJ has been established in the literature; however, the significance of this has not. The purpose of this study was to determine the rate of IPJ degenerative joint disease (DJD) in patients who underwent first MTPJ fusion by evaluating the degree of IPJ arthritic degeneration through 2 years post-surgery and to compare radiographic parameters over time among patients with and without DJD in order to determine whether non-fusion (less than 50% fusion) or the hallucal position was associated with the subsequent development of DJD. Methods: Retrospective clinical and radiographic review of patients who had undergone a first metatarsophalangeal joint arthrodesis was performed. Inclusion criteria were adult patients 18 and older who underwent first MPJ arthrodesis between January 2012 and January 2015 with internal fixation of any type. Patients were excluded if they were under 18 years of age, underwent concomitant procedures that would affect postoperative weight bearing course, suspected or diagnosed with osteomyelitis of the foot, had prior surgical procedures of the MTPJ or IPJ joints, or concomitant hallucal IPJ arthritis or preexisting IPJ fusion. Postoperative radiographs were obtained immediately following surgery and at approximately 6 weeks, 3 months, 6 months, 12 months, and 24 months. Results: Ultimately, 103 patients met all the inclusion criteria and none of the exclusion criteria. Four of the 103 patients (3.9%) had undergone bilateral procedures, thus providing 107 surgical procedures. Demographic characteristics can be found on Table 1. The hallux abductus (HA) angle and hallux abductus interphalangeus (HAI) angle were measured preoperatively and postoperatively (Fig. 1-2). The average postoperative follow-up radiograph was taken at 22.9 weeks. The HA angle average preoperatively was 31.4 degrees, which decreased to 11.8 degrees postoperatively. The HAI angle average preoperatively measured 10.8 degrees and increased to 11.9 degrees postoperatively. No patients had symptomatic hallux IPJ postoperatively within the study period. However, 7 patients needed hardware removal and second surgery at an average of 36.3 weeks due to hardware pain and nonunion. Conclusion: Arthrodesis is often the treatment of choice for first MTPJ pathology, which is commonly arthritis or hallux valgus. We found the incidence of IPJ arthritis to be lower than the reported literature and unchanged over the postoperative period. Furthermore, no patients reported symptomatic hallux IPJ within the study period. Also, we found the HA angle had decreased in the patients postoperatively; however, there was a mixed trend with HAI increasing after first MTPJ fusion. The significance of this trend is unclear, but the increase of the HAI could possibly cause further pain and deterioration of the joint in the future.


Life ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 3
Author(s):  
Yeri Alice Rim ◽  
Ji Hyeon Ju

Osteoarthritis (OA) is a chronic degenerative joint disease where the main characteristics include cartilage degeneration and synovial membrane inflammation. These changes in the knee joint eventually dampen the function of the joint and restrict joint movement, which eventually leads to a stage where total joint replacement is the only treatment option. While much is still unknown about the pathogenesis and progression mechanism of OA, joint fibrosis can be a critical issue for better understanding this disease. Synovial fibrosis and the generation of fibrocartilage are the two main fibrosis-related characteristics that can be found in OA. However, these two processes remain mostly misunderstood. In this review, we focus on the fibrosis process in OA, especially in the cartilage and the synovium tissue, which are the main tissues involved in OA.


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