scholarly journals IL-1β Damages Fibrocartilage and Upregulates MMP-13 Expression in Fibrochondrocytes in the Condyle of the Temporomandibular Joint

2019 ◽  
Vol 20 (9) ◽  
pp. 2260 ◽  
Author(s):  
Hessam Tabeian ◽  
Beatriz F. Betti ◽  
Cinthya dos Santos Cirqueira ◽  
Teun J. de Vries ◽  
Frank Lobbezoo ◽  
...  

The temporomandibular joint (TMJ), which differs anatomically and biochemically from hyaline cartilage-covered joints, is an under-recognized joint in arthritic disease, even though TMJ damage can have deleterious effects on physical appearance, pain and function. Here, we analyzed the effect of IL-1β, a cytokine highly expressed in arthritic joints, on TMJ fibrocartilage-derived cells, and we investigated the modulatory effect of mechanical loading on IL-1β-induced expression of catabolic enzymes. TMJ cartilage degradation was analyzed in 8–11-week-old mice deficient for IL-1 receptor antagonist (IL-1RA−/−) and wild-type controls. Cells were isolated from the juvenile porcine condyle, fossa, and disc, grown in agarose gels, and subjected to IL-1β (0.1–10 ng/mL) for 6 or 24 h. Expression of catabolic enzymes (ADAMTS and MMPs) was quantified by RT-qPCR and immunohistochemistry. Porcine condylar cells were stimulated with IL-1β for 12 h with IL-1β, followed by 8 h of 6% dynamic mechanical (tensile) strain, and gene expression of MMPs was quantified. Early signs of condylar cartilage damage were apparent in IL-1RA−/− mice. In porcine cells, IL-1β strongly increased expression of the aggrecanases ADAMTS4 and ADAMTS5 by fibrochondrocytes from the fossa (13-fold and 7-fold) and enhanced the number of MMP-13 protein-expressing condylar cells (8-fold). Mechanical loading significantly lowered (3-fold) IL-1β-induced MMP-13 gene expression by condylar fibrochondrocytes. IL-1β induces TMJ condylar cartilage damage, possibly by enhancing MMP-13 production. Mechanical loading reduces IL-1β-induced MMP-13 gene expression, suggesting that mechanical stimuli may prevent cartilage damage of the TMJ in arthritic patients.

2005 ◽  
Vol 289 (1) ◽  
pp. C148-C158 ◽  
Author(s):  
Nancy D. Searby ◽  
Charles R. Steele ◽  
Ruth K. Globus

Cells respond to a wide range of mechanical stimuli such as fluid shear and strain, although the contribution of gravity to cell structure and function is not understood. We hypothesized that bone-forming osteoblasts are sensitive to increased mechanical loading by hypergravity. A centrifuge suitable for cell culture was developed and validated, and then primary cultures of fetal rat calvarial osteoblasts at various stages of differentiation were mechanically loaded using hypergravity. We measured microtubule network morphology as well as release of the paracrine factor prostaglandin E2 (PGE2). In immature osteoblasts, a stimulus of 10× gravity (10 g) for 3 h increased PGE2 2.5-fold and decreased microtubule network height 1.12-fold without affecting cell viability. Hypergravity (3 h) caused dose-dependent (5–50 g) increases in PGE2 (5.3-fold at 50 g) and decreases (1.26-fold at 50 g) in microtubule network height. PGE2 release depended on duration but not orientation of the hypergravity load. As osteoblasts differentiated, sensitivity to hypergravity declined. We conclude that primary osteoblasts demonstrate dose- and duration-dependent sensitivity to gravitational loading, which appears to be blunted in mature osteoblasts.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Douglas S. Kalman ◽  
Susan J. Hewlings

The purpose of this study was to determine the effects of UP1306 on discomfort and function in adults with osteoarthritis of the knee. In a randomized, double-blinded, placebo-controlled, parallel design, 135 subjects received UP1306, a standardized, proprietary extract of Morus alba and Acacia catechu, glucosamine chondroitin, or placebo for 12 weeks. Discomfort, stiffness, and activities of daily living measured by the WOMAC questionnaire and VAS (pain/discomfort) were improved within all groups. Range of motion and distance walked were improved. There were no changes in TNFα levels for any of the products. There was a significant difference in urinary C-telopeptides of type II collagen (CTX-II), a marker of cartilage degradation between UP1306, and placebo after 12 weeks (p=0.029). All efficacy measurements were improved from baseline to most time-points for UP1306, the comparator, and placebo without a significant association between the products. There was a significant difference between the changes of uCTX-II for UP1306 and placebo after 12 weeks. Early intervention with UP1306 aimed at reducing bone and cartilage degradation through reported inhibition of catabolic proinflammatory pathways may help to prevent joint cartilage damage. This study is registered with Clinical Trial ID ISRCTN15418623.


2022 ◽  
Author(s):  
Jun Zhang ◽  
Yu Hu ◽  
Zihan Wang ◽  
Xuelian Wu ◽  
Chun Yang ◽  
...  

Abstract Background: It remains unclear whether hypoxic conditions affect apoptosis and contribute to degradation of cartilaginous tissues in osteoarthritis (OA) lesions. In this study, we hypothesized that hypoxic conditions induced the accumulation of hypoxia-inducible factor (HIF) and activated apoptosis to contribute to OA cartilage degeneration in vivo.Methods: Malocclusion stress was applied for 2 weeks, 4 weeks and 8 weeks to induce an OA-like lesion animal model (OD) in rats. Histological analysis was performed by H&E staining and safranin O/fast green staining. The expression levels of protein in condylar cartilage were examined by immunostaining to evaluate cartilage degeneration.Results: We found apparent histological phenotypes associated with degeneration in the occlusion disorder stress (OD) group. The OD group at 4 weeks and 8 weeks had obviously reduced expression of Acan and Col II in cartilage. In contrast, the OD groups had higher levels of Col X, ADAMTS5 and MMP13 in the condylar cartilage than the control group. Moreover, the OD group cartilage had prominent degenerative changes with reduced levels of HIF1α and increased levels of HIF2α and the apoptosis factor Caspase3 in condylar cartilage at 8 weeks.Occlusion disorder stress results in cartilage degeneration. HIF1α and HIF2α are involved in temporomandibular joint (TMJ) cartilage homeostasis by regulating chondrocyte apoptosis, which contributes to TMJ cartilage degeneration. Conclusion: Thus, abnormal hypoxic conditions inducing opposite expression patterns of HIF1α and HIF2α could be involved in the pathogenesis of condylar cartilage degeneration. HIF2α may provide a potential negative feedback mechanism for HIF1α during cartilage damage.


Arthritis ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
D. L. Bader ◽  
D. M. Salter ◽  
T. T. Chowdhury

There is an urgent demand for long term solutions to improve osteoarthritis treatments in the ageing population. There are drugs that control the pain but none that stop the progression of the disease in a safe and efficient way. Increased intervention efforts, augmented by early diagnosis and integrated biophysical therapies are therefore needed. Unfortunately, progress has been hampered due to the wide variety of experimental models which examine the effect of mechanical stimuli and inflammatory mediators on signal transduction pathways. Our understanding of the early mechanopathophysiology is poor, particularly the way in which mechanical stimuli influences cell function and regulates matrix synthesis. This makes it difficult to identify reliable targets and design new therapies. In addition, the effect of mechanical loading on matrix turnover is dependent on the nature of the mechanical stimulus. Accumulating evidence suggests that moderate mechanical loading helps to maintain cartilage integrity with a low turnover of matrix constituents. In contrast, nonphysiological mechanical signals are associated with increased cartilage damage and degenerative changes. This review will discuss the pathways regulated by compressive loading regimes and inflammatory signals in animal and in vitro 3D models. Identification of the chondroprotective pathways will reveal novel targets for osteoarthritis treatments.


2019 ◽  
Vol 7 (4) ◽  
pp. 543-548 ◽  
Author(s):  
Vivi Sofia ◽  
Ellyza Nasrul ◽  
Menkher Manjas ◽  
Gusti Revilla

BACKGROUND: Therapy that can cure osteoarthritis with satisfactory results has not been found to date. In the pathogenesis of osteoarthritis, the genes involved in cartilage degradation include the RELA gene which plays an important role in modulating the occurrence of cartilage damage, which involves activation of pro-inflammatory cytokines. One of the cytokines involved in the cartilage degradation process is Matrix Metalloproteinase (MMP) -13 which is also modulated by NFĸβ. AIM: This study aims to look at the expression of the RELA gene and expression of the MMP-13 gene and analyse the relationship of RELA gene expression with MMP-13 gene expression after administration of Mesenchymal Stem Cell Wharton Jelly in synoviocytes in vitro. MATERIAL AND METHODS: This research is pure experimental research. The samples used derived from synovial tissue in osteoarthritis patients who underwent surgery for Total Knee Replacement (TKR). This study was divided into 6 treatment groups with 4 replications. Group I was the synoviocyte OA cell control group which was incubated 24 hours, group II was control of synoviocyte OA cell which was incubated 48 hours, group III was a group of Mesenchymal Stem Cell Wharton Jelly (MSC-WJ) which was incubated 24 hours, group IV was a Mesenchymal Stem Cell Wharton Jelly (MSC-WJ) cell group incubated 48 hours, group V was the co-culture group of synoviocyte-MSC-WJ cells incubated 24 hours and group VI was the co-culture of synoviocyte-MSC-WJ cells which were incubated 48 hours. Observation of MMP-13 gene expression and RELA gene in each group was carried out using qPCR. RESULT: The results showed that the analysis of the relationship between RELA gene expression and MMP-13 gene expression in osteoarthritis synoviocytes cells after Mesenchymal Stem Cell Wharton Jelly as big as (r = 0.662). CONCLUSION: The conclusion of this study is there was a strong correlation between RELA gene expression and MMP-13 gene expression in osteoarthritis synoviocytes after Mesenchymal Stem Cell Wharton Jelly (r = 0.662).


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Chao Liang ◽  
Tao Yang ◽  
Gaoyi Wu ◽  
Jun Li ◽  
Wei Geng

Low-intensity pulsed ultrasound (LIPUS) is an emerging physical therapy for the treatment of early temporomandibular joint injury and has a good effect on promoting cartilage and subchondral bone tissue repair. However, the best LIPUS intensity and treatment duration remain unclear. This study is aimed at observing the preventive and therapeutic effects of different modes of LIPUS and at identifying the optimal LIPUS treatment regimen for temporomandibular joint injury. In the present study, rat models of temporomandibular joint injury were established using a chronic sleep deprivation (CSD) method, and the effect of LIPUS as intensities of 30, 45, and 60 mW/cm2 was observed at 7, 14, and 21 days. After CSD, the condylar cartilage of the rats demonstrated variable degrees of surface roughening, collagen fiber disarrangement or even partial exfoliation, decreased proteoglycan synthesis and cartilage thickness, decreased chondrocyte proliferation, decreased type 2 collagen (COL-2) expression, and increased matrix metalloproteinase- (MMP-) 3 expression at all three time points. When the rats with CSD received different intensities of LIPUS treatment, the pathological changes were alleviated to various extents. The groups receiving 45 mW/cm2 LIPUS showed the most significant relief of cartilage damage, and this significant effect was observed on days 14 and 21. These results demonstrated that LIPUS can effectively inhibit CSD-induced condylar cartilage damage in rats, and LIPUS treatment at an intensity of 45 mW/cm2 for at least 2 weeks is the optimal regimen for temporomandibular joint injury.


Cartilage ◽  
2015 ◽  
Vol 6 (3) ◽  
pp. 185-193 ◽  
Author(s):  
Oliver R. Schätti ◽  
Michala Marková ◽  
Peter A. Torzilli ◽  
Luigi M. Gallo

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