scholarly journals The Role of Wnt Pathway in the Pathogenesis of OA and Its Potential Therapeutic Implications in the Field of Regenerative Medicine

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Maria De Santis ◽  
Berardo Di Matteo ◽  
Emanuele Chisari ◽  
Gilberto Cincinelli ◽  
Peter Angele ◽  
...  

Introduction. Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation, subchondral damage, and bone remodelling, affecting most commonly weight-bearing joints, such as the knee and hip. The loss of cartilage leads to joint space narrowing, pain, and loss of function which could ultimately require total joint replacement. The Wnt/β catenin pathway is involved in the pathophysiology of OA and has been proposed as a therapeutic target. Endogenous and pharmacological inhibitors of this pathway were recently investigated within innovative therapies including the use of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs). Methods. A review of the literature was performed on the PubMed database based on the following inclusion criteria: article written in English language in the last 20 years and dealing with (1) the role of Wnt-β catenin pathway in the pathogenesis of osteoarthritis and (2) pharmacologic or biologic strategies modulating the Wnt-β catenin pathway in the OA setting. Results. Evidences support that Wnt signalling pathway is likely linked to OA progression and severity. Its inhibition through natural antagonists and new synthetic or biological drugs shares the potential to improve the clinical condition of the patients by affecting the pathological activity of Wnt/β-catenin signalling. Conclusions. While further research is needed to better understand the mechanisms regulating the molecular interaction between OA regenerative therapies and Wnt, it seems that biologic therapies for OA exert modulation on Wnt/β catenin pathway that might be relevant in achieving the beneficial clinical effect of those therapeutic strategies.

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.


2021 ◽  
Vol 17 ◽  
Author(s):  
Muhammad Tariq Rafiq ◽  
Mohamad Shariff Abdul Hamid ◽  
Eliza Hafiz ◽  
Khalid Rashid ◽  
Farid Ahmad Chaudhary

Introduction: Knee osteoarthritis (OA) is a weight-bearing joint disease and is more common in overweight and obese persons. The objective of this study was to determine the role of rehabilitation exercises (REs) of lower limbs on weight, functional strength, and exercise adherence in overweight and obese knee OA patients. Materials And Method: The patients were recruited from the Urban community of Lahore, Pakistan. The patients were divided into the rehabilitation group (RG) and control group (CG). The patients in the RG performed the REs of lower limbs and followed the instructions of daily care (IDC), while the patients in the CG only followed the IDC for 12 weeks. Outcome measures were assessed at pre-test before grouping and post-test after 12-weeks of interventions. The measures included: weight, functional strength, and exercise adherence. The Paired Samples t-test (for the normally distributed data) and the Wilcoxon Signed Ranked Test (for the data that was not normally distributed) were used to analyze the differences within groups from pre to post-test measurements. The analysis of variance 2 × 2 factors and the Mann-Whitney U-test were used to analyze the difference of weight and functional strength respectively between the groups. Results: The patients in the RG reported a statistically significant weight reduction (p < 0.001) and improvement in the functional strength (p < 0.001) within the group. Similarly, the patients in the CG also reported a significant improvement in the scores of functional strength (p = 0.004) within the group. The improvement in the scores of functional strength was greater in the patients of RG than the CG (p < 0.001. Similarly, the patients in the RG reported a statistically significant reduction in weight than the CG (p < 0.001). Conclusion: The REs could improve weight, functional strength and exercise adherence.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jiyuan Yan ◽  
Yingchi Zhang ◽  
Gaohong Sheng ◽  
Bowei Ni ◽  
Yifan Xiao ◽  
...  

Osteoarthritis (OA) is a prevalent degenerative joint disease. Its development is highly associated with inflammatory response and apoptosis in chondrocytes. Selonsertib (Ser), the inhibitor of Apoptosis Signal-regulated kinase-1 (ASK1), has exhibited multiple therapeutic effects in several diseases. However, the exact role of Ser in OA remains unclear. Herein, we investigated the anti-arthritic effects as well as the potential mechanism of Ser on rat OA. Our results showed that Ser could markedly prevent the IL-1β-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes. Meanwhile, the ASK1/P38/JNK and NFκB pathways were involved in the protective roles of Ser. Furthermore, intra-articular injection of Ser could significantly alleviate the surgery induced cartilage damage in rat OA model. In conclusion, our work provided insights into the therapeutic potential of Ser in OA, indicating that Ser might serve as a new avenue in OA treatment.


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.


2013 ◽  
Vol 29 (6) ◽  
pp. e23-e24
Author(s):  
Francesco Allegra ◽  
Fabio Cerza ◽  
Emanuele Delianni ◽  
Stefano El Boustany ◽  
Roberto Zannoni

2021 ◽  
Vol 24 (4) ◽  
pp. 601-607
Author(s):  
K. B Aminkov ◽  
N. H. Mehandzhiyski ◽  
B. Y. Aminkov ◽  
N. Z. Zlateva-Panayotova

Osteoarthritis, also known as degenerative joint disease (DJD), is defined as a progressive and permanent long-term deterioration of the cartilage surrounding the joints. There is no known cause for primary DJD. However, there are a wide variety of causes for secondary DJD, such as trauma, abnormal wear of joints and cartilage, or a congenital defect present at birth such as an improperly formed hip. One of the most popular methods used to biologically enhance healing in the fields of orthopaedic surgery and medicine includes the use of autologous blood products, namely, platelet rich plasma (PRP). Reports suggest that PRP, presumably containing high levels of platelet growth factors, may promote the recovery of the affected cartilage. This case series presents clinical and radiographic findings of three dogs with osteoarthritis of the elbow and knee joints. Pain score were assessed by CBPI (Canine Brief Pain Inventory). Treatment with three-fold intra-articular application of PRP, obtained by double centrifugation method, resulted in significant improvement in the function of the affected joint. Therefore, it could be concluded that PRP was clinically effective in the treatment of osteoarthritis in these three cases.


Bone Research ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Eugenie Macfarlane ◽  
Markus J. Seibel ◽  
Hong Zhou

Abstract Rheumatoid arthritis and osteoarthritis, the most common forms of arthritis, are chronic, painful, and disabling conditions. Although both diseases differ in etiology, they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage, bone, and synovium. While the potent anti-inflammatory properties of therapeutic (i.e., exogenous) glucocorticoids have been heavily researched and are widely used in clinical practice, the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly understood. Current evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in osteoarthritis. Furthermore, these models indicate that endogenous glucocorticoid signaling in macrophages, mast cells, and chondrocytes has anti-inflammatory effects, while signaling in fibroblast-like synoviocytes, myocytes, osteoblasts, and osteocytes has pro-inflammatory actions in rheumatoid arthritis. Conversely, in osteoarthritis, endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive actions. Together these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.


Author(s):  
Victor Ortiz-Declet ◽  
David A Iacobelli ◽  
Muriel R Battaglia ◽  
Cammille C Go ◽  
David R Maldonado ◽  
...  

Abstract We investigate whether platelet-rich plasma (PRP) injections can improve symptoms and function in patients with mild to moderate osteoarthritis (OA). Data were prospectively collected and retrospectively reviewed for all patients receiving PRP intra-articular hip injections between February 2017 and June 2017. The inclusion criteria were patients with a well-preserved joint space (Tönnis 0 or 1) whose magnetic resonance imaging (MRI) findings demonstrated degenerative joint disease or a Tönnis grade of 2. The patient-reported outcomes (PROs) used were the modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living Subscale (HOS-ADL), Hip Outcome Score-Sports Specific Subscale (HOS-SSS), International Hip Outcome TOOL (iHOT-12), Single Assessment Numeric Evaluation (SANE) and Mental and Physical aspects of the Veteran RAND 12 Item Health Survey (VR-12M and VR-12P). The visual analog scale (VAS) was utilized to indicate pain. Nine patients (11 hips) were eligible for inclusion. All PROs and VAS improved from pre- to post-injection. These improvements were present at the 3-month follow-up visit and stable until the 12-month follow-up. There was statistically significant improvement for mHHS (P &lt; 0.001), HOS-ADL (P = 0.006), iHOT-12 (P = 0.003) and VR-12M (P = 0.005) at 12 months post-injection. Similarly, VAS improved from 4.1 to 2.3, although the change was not statistically significant. PRP injections significantly improved PROs in all measured scales at time points up to a year after intervention, except for VR-12P and HOS-SSS. In conclusion, patients with early OA of the hip had significant improvement of patient-reported functional outcomes up to 12 months after PRP intra-articular injections.


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